Prostate Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Bladder Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Ovarian Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Pancreatic Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Testicular Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Breast Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Esophageal Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Cervical Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Liver Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Lung Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Colorectal Cancer Risk Prediction Models

Cancer.gov

Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Barriers to Cervical Cancer Screening among Middle-aged and Older Rural Appalachian Women

PubMed Central

Studts, Christina R.; Tarasenko, Yelena N.; Schoenberg, Nancy E.

2012-01-01

Although cervical cancer rates in the United States have declined sharply in recent decades, certain groups of women remain at elevated risk, including middle-aged and older women in central Appalachia. Cross-sectional baseline data from a community-based randomized controlled trial were examined to identify barriers to cervical cancer screening. Questionnaires assessing barriers were administered to 345 Appalachian women aged 40-64, years when Pap testing declines and cervical cancer rates increase. Consistent with the PRECEDE/PROCEED framework, participants identified barriers included predisposing, enabling, and reinforcing factors. Descriptive and bivariate analyses are reported, identifying (a) the most frequently endorsed barriers to screening, and (b) significant associations of barriers with sociodemographic characteristics in the sample. Recommendations are provided to decrease these barriers and, ultimately, improve rates of Pap tests among this traditionally underserved and disproportionately affected group. PMID:23179390

Triple Negative Breast Cancer Team Project — EDRN Public Portal

Cancer.gov

Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.

Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural diversity?

PubMed

Weidel, Elisabeth; Negri, Matthias; Empting, Martin; Hinsberger, Stefan; Hartmann, Rolf W

2014-01-01

In order to identify new scaffolds for drug discovery, surface plasmon resonance is frequently used to screen structurally diverse libraries. Usually, hit rates are low and identification processes are time consuming. Hence, approaches which improve hit rates and, thus, reduce the library size are required. In this work, we studied three often used strategies for their applicability to identify inhibitors of PqsD. In two of them, target-specific aspects like inhibition of a homologous protein or predicted binding determined by virtual screening were used for compound preselection. Finally, a fragment library, covering a large chemical space, was screened and served as comparison. Indeed, higher hit rates were observed for methods employing preselected libraries indicating that target-oriented compound selection provides a time-effective alternative.

Risk Prediction Models for Other Cancers or Multiple Sites

Cancer.gov

Developing statistical models that estimate the probability of developing other multiple cancers over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

Newborn screening 50 years later: access issues faced by adults with PKU

PubMed Central

Berry, Susan A.; Brown, Christine; Grant, Mitzie; Greene, Carol L.; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C.; Wiles, Judy; Cederbaum, Stephen

2013-01-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease. Genet Med 2013:15(8):591–599 PMID:23470838

Newborn screening 50 years later: access issues faced by adults with PKU.

PubMed

Berry, Susan A; Brown, Christine; Grant, Mitzie; Greene, Carol L; Jurecki, Elaina; Koch, Jean; Moseley, Kathryn; Suter, Ruth; van Calcar, Sandra C; Wiles, Judy; Cederbaum, Stephen

2013-08-01

Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.

Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach.

PubMed

Hartman, Douglas J; Brand, Randall E; Hu, Huankai; Bahary, Nathan; Dudley, Beth; Chiosea, Simon I; Nikiforova, Marina N; Pai, Reetesh K

2013-11-01

The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas. © 2013.

MNSs Blood Group Glycophorin Variants in Taiwan: A Genotype-Serotype Correlation Study of ‘Mia’ and Sta with Report of Two New Alleles for Sta

PubMed Central

Chen, Tai-Di; Chen, Ding-Ping; Wang, Wei-Ting; Sun, Chien-Feng

2014-01-01

Background Glycophorin variants of the MNSs blood group are important in Taiwan. For more than 20 years, screening for the most frequent irregular antibody, anti-‘Mia’, has been conducted by using ‘Mia’(+) RBCs, with a significant success. However, the sensitivity and the specificity of this screening strategy have never been validated, and the true incidences of different glycophorin variants in Taiwan have been in controversy. Also, the significance of another less frequent and usually separately reported variant, Sta, has never been evaluated. Methodology/Principal Findings We ran a population-based screening (from unselected patients in our hospital) for MNSs blood group glycophorin variants by PCR-sequencing method. GP.Mur (Mil.III) was confirmed by sequence from 57 out of 1027 samples (5.6%), and there was no other Miltenberger subtype glycophorin variant found. Glycophorin variant Sta was found from 35 out of 1027 samples (3.4%). In contrast to anti-‘Mia’, which is the most frequently identified irregular antibody in Taiwan, the prevalence of anti-Sta was only 0.13% as determined by serologic method. In addition, two new alleles for Sta were found and reported. Conclusion/Significance We confirm the long-standing assumption that GP.Mur is the only prevalent Miltenberger subtype in Taiwan. The current anti-‘Mia’ screening method used in Taiwan, although neither sensitive nor specific, is still a suitable practice. Although Sta antigen has a high prevalence in Taiwan, routine screening for anti-Sta is not warranted based on current evidence. PMID:24858913

Identifying CNVs in 15q11q13 and 16p11.2 of Patients with Seizures Increases the Rates of Detecting Pathogenic Changes

PubMed Central

Vianna, Gabrielle S.; Freitas, Mariana L.; Oliveira, Valdirene T.de; Pietra, Rafaella X.; Gonçalves, Michele da S.; Rocha, Patrícia P.O.; Monteiro, Rejane A.C.; Ferreira, Luana C.A.; Xavier, Rosana R.; Carvalho, Andréia M.; Lima, Patrícia R. de M.; Monteiro, Maria Augusta N.P.; Mateo, Elvis C.; Giannetti, Juliana G.; César, Giovana da C.; Lima, Joziele de S.; Medeiros, Paula F.V.; Jehee, Fernanda S.

2016-01-01

Chromosomal changes are frequently observed in patients with syndromic seizures. Understanding the genetic etiology of this pathology is crucial for the guidance and genetic counseling of families as well as for the establishment of appropriate treatment. A combination of MLPA kits was used to identify pathogenic CNVs in a group of 70 syndromic patients with seizures. Initially, a screening was performed for subtelomeric changes (MLPA P036 and P070 kits) and for the regions most frequently related to microdeletion/microduplication syndromes (MLPA P064). Subsequently, the MLPA P343 was used to identify alterations in the 15q11q13, 16p11.2, and 22q13 regions. Screening with MLPA P343 allowed a 10-15.7% increase in the detection rate of CNVs reinforcing the importance of investigating changes in 15q11q13 and 16p11.2 in syndromic patients with seizures. We also demonstrated that the MLPA technique is an alternative with a great diagnostic potential, and we proposed its use as part of the initial assessment of syndromic patients with seizures. PMID:27920636

Optimal screening and donor management in a public stool bank.

PubMed

Kazerouni, Abbas; Burgess, James; Burns, Laura J; Wein, Lawrence M

2015-12-17

Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.

Impact of Patient Reminders on Papanicolaou Test Completion for High-Risk Patients Identified by a Clinical Decision Support System.

PubMed

MacLaughlin, Kathy L; Kessler, Maya E; Komandur Elayavilli, Ravikumar; Hickey, Branden C; Scheitel, Marianne R; Wagholikar, Kavishwar B; Liu, Hongfang; Kremers, Walter K; Chaudhry, Rajeev

2018-05-01

A clinical decision support system (CDSS) for cervical cancer screening identifies patients due for routine cervical cancer screening. Yet, high-risk patients who require more frequent screening or earlier follow-up to address past abnormal results are not identified. We aimed to assess the effect of a complex CDSS, incorporating national guidelines for high-risk patient screening and abnormal result management, its implementation to identify patients overdue for testing, and the outcome of sending a targeted recommendation for follow-up. At three primary care clinics affiliated with an academic medical center, a reminder recommending an appointment for Papanicolaou (Pap) testing or Pap and human papillomavirus cotesting was sent to high-risk women aged 18 through 65 years (intervention group) identified by CDSS as overdue for testing. Historical control patients, who did not receive a reminder, were identified by CDSS 1 year before the date when reminders were sent to the intervention group. Test completion rates were compared between the intervention and control groups through a generalized estimating equation extension. Across the three sites, the average completion rate of recommended follow-up testing was significantly higher in the intervention group at 23.7% (61/257) than the completion rate at 3.3% (17/516) in the control group (p < 0.001). A CDSS with enhanced capabilities to identify high-risk women due for cervical cancer testing beyond routine screening intervals, with subsequent patient notification, has the potential to decrease cervical precancer and cancer by improving adherence to guideline-compliant follow-up and needed treatment.

Older women and breast cancer screening: research synthesis.

PubMed

Yarbrough, Suzanne S

2004-01-01

To identify the most beneficial ways to support older women as they make screening decisions using a systematic, epidemiologic, narrative review of research regarding benefits and burdens of breast cancer screening and treatment. Medical and nursing research databases emphasizing women aged 60 and older. Older women can tolerate screening and treatment, yet they are underserved. The most frequently cited reason to explain this phenomenon is declining health status associated with aging. Research evidence does not support this claim. No evidence clearly describes relationships among health status, aging, and less screening or less aggressive treatment. Older women experience varied health problems. However, indications that they are less able than their younger counterparts to tolerate screening or treatment for breast cancer do not exist. Further research in all aspects of breast cancer care in older women is required to define and describe risks and benefits of screening within a context of aging and changing health. Nurses should discuss the risks and benefits of screening with older women.

An object lesson: source determines the relations that trait anxiety, prostate cancer worry, and screening fear hold with prostate screening frequency.

PubMed

Consedine, Nathan S; Adjei, Brenda A; Ramirez, Paul M; McKiernan, James M

2008-07-01

Fears regarding prostate cancer and the associated screening are widespread. However, the relations between anxiety, cancer worry, and screening fear and screening behavior are complex, because anxieties stemming from different sources have different effects on behavior. In differentiating among anxieties from different sources (trait anxiety, cancer worry, and screening fear), we expected that cancer worry would be associated with more frequent screening, whereas fear of screening would be associated with less frequent screening. Hypotheses were tested in a sample of 533 men (ages 45-70 years) recruited using a stratified cluster-sampling plan. Men provided information on demographic and structural variables (age, education, income, marital status, physician discussion of risk and screening, access, and insurance) and completed a set of anxiety measures (trait anxiety, cancer worry, and screening fear). As expected, two-step multiple regressions controlling for demographics, health insurance status, physician discussion, and health-care system barriers showed that prostate-specific antigen and digital rectal examination frequencies had unique associations with cancer worry and screening fear. Specifically, whereas cancer worry was associated with more frequent screening, fear of screening was associated with less frequent screening at least for digital rectal examination; trait anxiety was inconsistently related to screening. Data are discussed in terms of their implications for male screening and the understanding of how anxiety motivates health behaviors. It is suggested that understanding the source of anxiety and the manner in which health behaviors such as cancer screenings may enhance or reduce felt anxiety is a likely key to understanding the associations between anxiety and behavioral outcomes.

Cost and effects of different admission screening strategies to control the spread of methicillin-resistant Staphylococcus aureus.

PubMed

Gurieva, Tanya; Bootsma, Martin C J; Bonten, Marc J M

2013-01-01

Nosocomial infection rates due to antibiotic-resistant bacteriae, e.g., methicillin-resistant Staphylococcus aureus (MRSA) remain high in most countries. Screening for MRSA carriage followed by barrier precautions for documented carriers (so-called screen and isolate (S&I)) has been successful in some, but not all settings. Moreover, different strategies have been proposed, but comparative studies determining their relative effects and costs are not available. We, therefore, used a mathematical model to evaluate the effect and costs of different S&I strategies and to identify the critical parameters for this outcome. The dynamic stochastic simulation model consists of 3 hospitals with general wards and intensive care units (ICUs) and incorporates readmission of carriers of MRSA. Patient flow between ICUs and wards was based on real observations. Baseline prevalence of MRSA was set at 20% in ICUs and hospital-wide at 5%; ranges of costs and infection rates were based on published data. Four S&I strategies were compared to a do-nothing scenario: S&I of previously documented carriers ("flagged" patients); S&I of flagged patients and ICU admissions; S&I of flagged and group of "frequent" patients; S&I of all hospital admissions (universal screening). Evaluated levels of efficacy of S&I were 10%, 25%, 50% and 100%. Our model predicts that S&I of flagged and S&I of flagged and ICU patients are the most cost-saving strategies with fastest return of investment. For low isolation efficacy universal screening and S&I of flagged and "frequent" patients may never become cost-saving. Universal screening is predicted to prevent hardly more infections than S&I of flagged and "frequent" patients, albeit at higher costs. Whether an intervention becomes cost-saving within 10 years critically depends on costs per infection in ICU, costs of screening and isolation efficacy.

A Genome-Wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells

PubMed Central

Zhang, Eric E.; Liu, Andrew C.; Hirota, Tsuyoshi; Miraglia, Loren J.; Welch, Genevieve; Pongsawakul, Pagkapol Y.; Liu, Xianzhong; Atwood, Ann; Huss, Jon W.; Janes, Jeff; Su, Andrew I.; Hogenesch, John B.; Kay, Steve A.

2009-01-01

Summary Two decades of research identified more than a dozen clock genes and defined a biochemical feedback mechanism of circadian oscillator function. To identify additional clock genes and modifiers, we conducted a genome-wide siRNA screen in a human cellular clock model. Knockdown of nearly a thousand genes reduced rhythm amplitude. Potent effects on period length or increased amplitude were less frequent; we found hundreds of these and confirmed them in secondary screens. Characterization of a subset of these genes demonstrated a dosage-dependent effect on oscillator function. Protein interaction network analysis showed that dozens of gene products directly or indirectly associate with known clock components. Pathway analysis revealed these genes are overrepresented for components of insulin and hedgehog signaling, the cell cycle, and the folate metabolism. Coupled with data showing many of these pathways are clock-regulated, we conclude the clock is interconnected with many aspects of cellular function. PMID:19765810

A rapid screening with direct sequencing from blood samples for the diagnosis of Leigh syndrome.

PubMed

Shimbo, Hiroko; Takagi, Mariko; Okuda, Mitsuko; Tsuyusaki, Yu; Takano, Kyoko; Iai, Mizue; Yamashita, Sumimasa; Murayama, Kei; Ohtake, Akira; Goto, Yu-Ichi; Aida, Noriko; Osaka, Hitoshi

2014-01-01

Large numbers of genes are responsible for Leigh syndrome (LS), making genetic confirmation of LS difficult. We screened our patients with LS using a limited set of 21 primers encompassing the frequently reported gene for the respiratory chain complexes I (ND1-ND6, and ND4L), IV(SURF1), and V(ATP6) and the pyruvate dehydrogenase E1α-subunit. Of 18 LS patients, we identified mutations in 11 patients, including 7 in mDNA (two with ATP6), 4 in nuclear (three with SURF1). Overall, we identified mutations in 61% of LS patients (11/18 individuals) in this cohort. Sanger sequencing with our limited set of primers allowed us a rapid genetic confirmation of more than half of the LS patients and it appears to be efficient as a primary genetic screening in this cohort.

Geriatric screening in first opinion practice – results from 45 dogs

PubMed Central

Davies, M

2012-01-01

Objectives To evaluate and report the results of screening geriatric dogs in a first opinion practice. Methods A prospective health screen of dogs over nine-years-old involving history taking, physical examination and urinalysis. Results At least one previously unrecognised problem was identified in 80% of 45 dogs and 353 findings (mean 7·8 per dog) were recorded. Owners often failed to recognise and report serious signs of age-related disease. However, they most often reported increased sleeping (31%), loss of hearing (29%) or sight (20%), stiffness or lameness (22%) and “slowing down” (20%). Increased lens opacity (64%), increased thirst (58%), pain (24%), increased frequency of urination (24%), signs of osteoarthritis (24%) and dental disease (22%) were most frequently identified at the time of consultation. Potentially, life-threatening findings included respiratory distress, palpable abdominal masses and metastatic lung disease. Screening resulted in 29 further diagnostic procedures, including 10 dental procedures, seven medical treatments, two surgical procedures and euthanasia of two dogs. Clinical Significance Screening elderly dogs identified unrecognised and unreported health risk factors resulting in lifestyle modification and ongoing monitoring, as well as signs of age-related diseases resulting in diagnostic investigations, early diagnoses and surgical and medical interventions to improve quality of life. PMID:22835038

Geriatric screening in first opinion practice - results from 45 dogs.

PubMed

Davies, M

2012-09-01

To evaluate and report the results of screening geriatric dogs in a first opinion practice. A prospective health screen of dogs over nine-years-old involving history taking, physical examination and urinalysis. At least one previously unrecognised problem was identified in 80% of 45 dogs and 353 findings (mean 7·8 per dog) were recorded. Owners often failed to recognise and report serious signs of age-related disease. However, they most often reported increased sleeping (31%), loss of hearing (29%) or sight (20%), stiffness or lameness (22%) and "slowing down" (20%). Increased lens opacity (64%), increased thirst (58%), pain (24%), increased frequency of urination (24%), signs of osteoarthritis (24%) and dental disease (22%) were most frequently identified at the time of consultation. Potentially, life-threatening findings included respiratory distress, palpable abdominal masses and metastatic lung disease. Screening resulted in 29 further diagnostic procedures, including 10 dental procedures, seven medical treatments, two surgical procedures and euthanasia of two dogs. Screening elderly dogs identified unrecognised and unreported health risk factors resulting in lifestyle modification and ongoing monitoring, as well as signs of age-related diseases resulting in diagnostic investigations, early diagnoses and surgical and medical interventions to improve quality of life. © 2012 British Small Animal Veterinary Association.

MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer.

PubMed

Theodorou, Vassiliki; Kimm, Melanie A; Boer, Mandy; Wessels, Lodewyk; Theelen, Wendy; Jonkers, Jos; Hilkens, John

2007-06-01

We performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated with mammary cancer and 13 had not previously been linked to cancer in general. Although members of the Wnt and fibroblast growth factors (Fgf) families were frequently tagged, our exhaustive screening for MMTV insertion sites uncovered a new repertoire of candidate breast cancer oncogenes. We validated one of these genes, Rspo3, as an oncogene by overexpression in a p53-deficient mammary epithelial cell line. The human orthologs of the candidate oncogenes were frequently deregulated in human breast cancers and associated with several tumor parameters. Computational analysis of all MMTV-tagged genes uncovered specific gene families not previously associated with cancer and showed a significant overrepresentation of protein domains and signaling pathways mainly associated with development and growth factor signaling. Comparison of all tagged genes in MMTV and Moloney murine leukemia virus-induced malignancies showed that both viruses target mostly different genes that act predominantly in distinct pathways.

An Assessment of the Likelihood, Frequency, and Content of Verbal Communication Between Radiologists and Women Receiving Screening and Diagnostic Mammography

PubMed Central

Carney, Patricia A.; Kettler, Mark; Cook, Andrea J.; Geller, Berta M.; Karliner, Leah; Miglioretti, Diana L.; Bowles, Erin Aiello; Buist, Diana S.; Gallagher, Thomas H.; Elmore, Joann G.

2009-01-01

Rationale & Objective Research on communication between radiologists and women undergoing screening and diagnostic mammography is limited. We describe community radiologists’ communication practices with patients regarding screening and diagnostic mammogram results and factors associated with frequency of communication. Materials & Methods We received surveys from 257 radiologists (70% of those eligible) about the extent to which they talk to women as part of their healthcare visit for either screening or diagnostic mammograms, whether this occurs if the exam assessment is positive or negative, and how they use estimates of patient risk to convey information about an abnormal exam where the specific finding of cancer is not yet known. We also assessed characteristics of the radiologists to identify associations with more or less frequent communication at the time of the mammogram. Results Two hundred and forty-three radiologists provided complete data (95%). Very few (<6%) reported routinely communicating with women when screening mammograms were either normal or abnormal. Less than half (47%) routinely communicated with women when their diagnostic mammograms were normal, while 77% often or always communicated with women when their diagnostic exams were abnormal. For positive diagnostic exams, female radiologists were more likely to be frequent communicators compared to males (87.1% to 72.8%; p-value = 0.02) and those who spend 40-79% of their time in breast imaging (94.6%) were more likely to be frequent communicators compared to those who spend less time (67.2%-78.9%; p-value = 0.02). Most radiologists convey risk information using general rather than numeric statements (57.7% vs. 28.5%). Conclusions Radiologists are most likely to convey information about diagnostic mammographic findings when results are abnormal. Most radiologists convey risk information using general rather than numeric statements. PMID:19442539

Suicide Risk Screening Tools and the Youth Population.

PubMed

Patterson, Sharon

2016-08-01

The use of suicide risk screening tools is a critical component of a comprehensive approach to suicide risk assessment. Since nurses frequently spend more time with patients than any other healthcare professional, they are in key positions to detect and prevent suicidal behavior in youth. To inform nurses about suicide risk screening tools for the youth population. Suicide risk screening tools are research-based standardized instruments that are used to identify people who may be at risk for suicide. A literature search was performed using the Athabasca University Library Resource, the databases of the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, and Google Scholar. Nurses are cautioned to utilize suicide risk screening tools as only part of the suicide risk assessment in youth populations and avoid the danger of relying on tools that may result in a blind application of evidence to the detriment of clinical experience and judgement. © 2016 Wiley Periodicals, Inc.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature.

PubMed

Alharthi, Abdulla A; El-Hallous, Ehab I; Talaat, Iman M; Alghamdi, Hamed A; Almalki, Matar I; Gaber, Ahmed

2017-10-01

Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene ( SHOX ) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX . In Saudi Arabia ISS patients, rather than SHOX , it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Preconceptional identification of cystic fibrosis carriers in the Sardinian population: A pilot screening program.

PubMed

Coiana, Alessandra; Faa', Valeria; Carta, Daniela; Puddu, Rosalba; Cao, Antonio; Rosatelli, Maria Cristina

2011-05-01

In Sardinia the mutational spectrum of CFTR gene is well defined. A mutation detection rate of 94% can be achieved by screening for 15 CFTR mutations with a frequency higher than 0.5%. The efficiency of this molecular test suggests that Sardinians may represent a suitable population for a preconceptional screening. Five hundred couples of Sardinia descent were screened for 38 mutations using a semi-automated reverse-dot blot and PCR-gel electrophoresis assays. This mutation panel included the 15 most frequent CF alleles in Sardinia. We identified 38 CF carriers, revealing an overall frequency of 1/25 (4%). The most common CF allele was the p.Thr338Ile (T338I) (65%), followed by the p.Phe508del (F508del) (22.5%). We also identified one couple at risk and an asymptomatic female homozygote for the p.Thr338Ile allele. In spite of the low number of the couples tested, the results herein reported demonstrate the efficacy and efficiency of the preconceptional screening program and the high participation rate of the Sardinian population (99%). Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Decline in Cancer Screening in Vulnerable Populations? Results of the EDIFICE Surveys.

PubMed

Morère, Jean-François; Eisinger, François; Touboul, Chantal; Lhomel, Christine; Couraud, Sébastien; Viguier, Jérôme

2018-03-05

We studied cancer screening over time and social vulnerability via surveys of representative populations. Individuals aged 50-75 years with no personal history of cancer were questioned about lifetime participation in screening tests, compliance (adherence to recommended intervals [colorectal, breast and cervical cancer]) and opportunistic screening (prostate and lung cancer). The proportion of vulnerable/non-vulnerable individuals remained stable between 2011 and 2016. In 2011, social vulnerability had no impact on screening participation, nor on compliance. In 2014, however, vulnerability was correlated with less frequent uptake of colorectal screening (despite an organised programme) and prostate cancer screening (opportunistic), and also with reduced compliance with recommended intervals (breast and cervical cancer screening). In 2016, the trends observed in 2014 were substantiated and even extended to breast, colorectal and cervical cancer screening uptakes. Social vulnerability has an increasingly negative impact on cancer screening attendance. The phenomenon was identified in 2014 and had expanded by 2016. Although organised programmes have been shown to ensure equitable access to cancer screening, this remains a precarious achievement requiring regular monitoring. Further studies should focus on attitudes of vulnerable populations and on ways to improve cancer awareness campaigns.

Informing Active Play and Screen Time Behaviour Change Interventions for Low Socioeconomic Position Mothers of Young Children: What Do Mothers Want?

PubMed Central

Campbell, Karen J.; Hesketh, Kylie D.

2016-01-01

Introduction. This study investigated views of mothers from disadvantaged urban and regional areas (i.e., beyond major capital cities) as potential end users of child active play and screen time behaviour change interventions, with a focus on text messaging and web-based delivery platforms. Methods. Thirty-two mothers (22 urban; 10 regional) were interviewed. Purpose-designed questions covered topics regarding mothers' preferences for accessing and receiving information related to parenting and child active play and screen time. Data from transcribed interviews were analysed to identify responses and key themes. Results. Mothers reported frequently accessing parenting- and child-related information online. Regional mothers reported seeking information by talking with other people less frequently than urban mothers and seemed to have a stronger preference for receiving information online. There were few differences between responses from low and high educated mothers. The majority of mothers reported that they would be happy to receive text messages containing information about active play and screen time and that they would find a dedicated website with this information useful. Conclusions. Mothers in this study held favourable views on the potential of receiving information via new communication technologies. Future interventions targeting socioeconomically disadvantaged mothers may benefit from delivering intervention messages via these technologies. PMID:28053979

Analyzing the most frequent disease loci in targeted patient categories optimizes disease gene identification and test accuracy worldwide.

PubMed

Lebo, Roger V; Tonk, Vijay S

2015-01-21

Our genomewide studies support targeted testing the most frequent genetic diseases by patient category: (1) pregnant patients, (2) at-risk conceptuses, (3) affected children, and (4) abnormal adults. This approach not only identifies most reported disease causing sequences accurately, but also minimizes incorrectly identified additional disease causing loci. Diseases were grouped in descending order of occurrence from four data sets: (1) GeneTests 534 listed population prevalences, (2) 4129 high risk prenatal karyotypes, (3) 1265 affected patient microarrays, and (4) reanalysis of 25,452 asymptomatic patient results screened prenatally for 108 genetic diseases. These most frequent diseases are categorized by transmission: (A) autosomal recessive, (B) X-linked, (C) autosomal dominant, (D) microscopic chromosome rearrangements, (E) submicroscopic copy number changes, and (F) frequent ethnic diseases. Among affected and carrier patients worldwide, most reported mutant genes would be identified correctly according to one of four patient categories from at-risk couples with <64 tested genes to affected adults with 314 tested loci. Three clinically reported patient series confirmed this approach. First, only 54 targeted chromosomal sites would have detected all 938 microscopically visible unbalanced karyotypes among 4129 karyotyped POC, CVS, and amniocentesis samples. Second, 37 of 48 reported aneuploid regions were found among our 1265 clinical microarrays confirming the locations of 8 schizophrenia loci and 20 aneuploidies altering intellectual ability, while also identifying 9 of the most frequent deletion syndromes. Third, testing 15 frequent genes would have identified 124 couples with a 1 in 4 risk of a fetus with a recessive disease compared to the 127 couples identified by testing all 108 genes, while testing all mutations in 15 genes could have identified more couples. Testing the most frequent disease causing abnormalities in 1 of 8 reported disease loci [~1 of 84 total genes] will identify ~ 7 of 8 reported abnormal Caucasian newborn genotypes. This would eliminate ~8 to 10 of ~10 Caucasian newborn gene sequences selected as abnormal that are actually normal variants identified when testing all ~2500 diseases looking for the remaining 1 of 8 disease causing genes. This approach enables more accurate testing within available laboratory and reimbursement resources.

Adherence to cancer screening guidelines and predictors of improvement among participants in the Kansas State Employee Wellness Program.

PubMed

Hui, Siu-kuen Azor; Engelman, Kimberly K; Shireman, Theresa I; Ellerbeck, Edward F

2013-07-11

Employee wellness programs (EWPs) have been used to implement worksite-based cancer prevention and control interventions. However, little is known about whether these programs result in improved adherence to cancer screening guidelines or how participants' characteristics affect subsequent screening. This study was conducted to describe cancer screening behaviors among participants in a state EWP and identify factors associated with screening adherence among those who were initially nonadherent. We identified employees and their dependents who completed health risk assessments (HRAs) as part of the Kansas state EWP in both 2008 and 2009. We examined baseline rates of adherence to cancer screening guidelines in 2008 and factors associated with adherence in 2009 among participants who were initially nonadherent. Of 53,095 eligible participants, 13,222 (25%) participated in the EWP in 2008 and 6,205 (12%) participated in both years. Among the multiyear participants, adherence was high at baseline to screening for breast (92.5%), cervical (91.8%), and colorectal cancer (72.7%). Of participants who were initially nonadherent in 2008, 52.4%, 41.3%, and 33.5%, respectively, became adherent in the following year to breast, cervical, and colorectal cancer screening. Suburban/urban residence and more frequent doctor visits predicted adherence to breast and colorectal cancer screening guidelines. The effectiveness of EWPs for increasing cancer screening is limited by low HRA participation rates, high rates of adherence to screening at baseline, and failure of nonadherent participants to get screening. Improving overall adherence to cancer screening guidelines among employees will require efforts to increase HRA participation, stronger interventions for nonadherent participants, and better access to screening for rural employees.

Adherence to Cancer Screening Guidelines and Predictors of Improvement Among Participants in the Kansas State Employee Wellness Program

PubMed Central

Engelman, Kimberly K.; Shireman, Theresa I.; Ellerbeck, Edward F.

2013-01-01

Introduction Employee wellness programs (EWPs) have been used to implement worksite-based cancer prevention and control interventions. However, little is known about whether these programs result in improved adherence to cancer screening guidelines or how participants’ characteristics affect subsequent screening. This study was conducted to describe cancer screening behaviors among participants in a state EWP and identify factors associated with screening adherence among those who were initially nonadherent. Methods We identified employees and their dependents who completed health risk assessments (HRAs) as part of the Kansas state EWP in both 2008 and 2009. We examined baseline rates of adherence to cancer screening guidelines in 2008 and factors associated with adherence in 2009 among participants who were initially nonadherent. Results Of 53,095 eligible participants, 13,222 (25%) participated in the EWP in 2008 and 6,205 (12%) participated in both years. Among the multiyear participants, adherence was high at baseline to screening for breast (92.5%), cervical (91.8%), and colorectal cancer (72.7%). Of participants who were initially nonadherent in 2008, 52.4%, 41.3%, and 33.5%, respectively, became adherent in the following year to breast, cervical, and colorectal cancer screening. Suburban/urban residence and more frequent doctor visits predicted adherence to breast and colorectal cancer screening guidelines. Conclusion The effectiveness of EWPs for increasing cancer screening is limited by low HRA participation rates, high rates of adherence to screening at baseline, and failure of nonadherent participants to get screening. Improving overall adherence to cancer screening guidelines among employees will require efforts to increase HRA participation, stronger interventions for nonadherent participants, and better access to screening for rural employees. PMID:23845176

Mammography Screening Uptake among Female Health Care Workers in Primary Health Care Centers in Palestine - Motivators and Barriers.

PubMed

Nazzal, Zaher; Sholi, Hisham; Sholi, Suha; Sholi, Mohammad; Lahaseh, Rawya

2016-01-01

Early detection remains the cornerstone of breast cancer control in terms of outcome and survival. Thus far the only breast cancer screening method proven effective is mammography. The awareness of female health care workers (HCW) about breast cancer prevention is of vital importance, as their beliefs and behavior may have a major impact on other women. This study was designed to assess mammography screening uptake among female healthcare workers at primary healthcare centers, and to identify the primary motivators and barriers that affect uptake results. A cross sectional study design was used to assess mammography screening by 299 female healthcare workers who completed a self-administered questionnaire that assessed demographics, screening uptake, motivators and barriers. The mean age was 46 years (within age of risk). The majority (95.1%) demonstrated adequate knowledge about breast cancer and mammography screening and 50% of the participants reported having at least one mammogram; however only 21% of them had regularly scheduled mammograms. The most frequent reported motivator was the perceived benefit that early detection of breast cancer is important for its management (89.6%), followed by the belief that mammography can detect breast cancer before its symptoms appear (84.4%). On the other hand, the most frequent barrier reported was being busy (46.7%), followed by the lack of perceived susceptibility (41.5%). Mammography screening was found to be sub-optimal in a population of HCW's with 50 % stating that they received a mammogram at least once, and a minority reported regular screening. There is a pressing need for educational programs aimed at removing the barriers that limit compliance with recommendations for mammography screening, and to emphasize the importance of early detection in breast cancer treatment. Ensuring the availability and accessibility of screening services, particularly for healthcare workers within their work settings are other important factors that would improve the acceptance and compliance for mammography screening programs.

Prevalence and Patterns of Learning Disabilities in School Children.

PubMed

Padhy, Susanta Kumar; Goel, Sonu; Das, Shyam Sinder; Sarkar, Siddharth; Sharma, Vijaylaxmi; Panigrahi, Mahima

2016-04-01

To assess the prevalence and patterns of learning disabilities (LD) in school going children in a northern city of India. The present cross-sectional study comprised of three-staged screening procedure for assessing learning disabilities of 3rd and 4th grade students studying in government schools. The first stage comprised of the teacher identifying at-risk student. In the second stage, teachers assessed at-risk students using Specific Learning Disability-Screening Questionnaire (SLD-SQ). The third stage comprised of assessment of the screen positive students using Brigance Diagnostic Inventory (BDI) part of NIMHANS Index of Specific Learning Disabilities for identifying the cases of LD. A total of 1211 (33.6%) children out of the total screened (n = 3600) were identified as at-risk by the teachers at the first stage. Of them, 360 were found to screen positive on the second stage using SLD-SQ. The most common deficits were missing out words or sentences while reading, misplacing letters or words while reading or writing, and making frequent mistake in spelling while writing or reading. Of these, 108 children were confirmed to have learning disability on the third stage using BDI, which represented 3.08% of the total population. Learning disability is an important concern in young school aged children. Early identification of such students can help in early institution of intervention and suitable modifications in teaching techniques.

Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry.

PubMed

Meng, Juncai; Lai, Ming-Tain; Munshi, Vandna; Grobler, Jay; McCauley, John; Zuck, Paul; Johnson, Eric N; Uebele, Victor N; Hermes, Jeffrey D; Adam, Gregory C

2015-06-01

HIV-1 protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. To identify novel PR inhibitors, a label-free, high-throughput mass spectrometry (HTMS) assay was developed using the RapidFire platform and applied as an orthogonal assay to confirm hits identified in a fluorescence resonance energy transfer (FRET)-based primary screen of > 1 million compounds. For substrate selection, a panel of peptide substrates derived from natural processing sites for PR was evaluated on the RapidFire platform. As a result, KVSLNFPIL, a new substrate measured to have a ~ 20- and 60-fold improvement in k cat/K m over the frequently used sequences SQNYPIVQ and SQNYPIV, respectively, was identified for the HTMS screen. About 17% of hits from the FRET-based primary screen were confirmed in the HTMS confirmatory assay including all 304 known PR inhibitors in the set, demonstrating that the HTMS assay is effective at triaging false-positives while capturing true hits. Hence, with a sampling rate of ~7 s per well, the RapidFire HTMS assay enables the high-throughput evaluation of peptide substrates and functions as an efficient tool for hits triage in the discovery of novel PR inhibitors. © 2015 Society for Laboratory Automation and Screening.

Risk factors for peri-traumatic distress and appearance concerns in burn-injured inpatients identified by a screening tool

PubMed Central

Oaie, Ecaterina; Piepenstock, Emma; Williams, Lisa

2018-01-01

Introduction: Psychosocial screening of burn-injured patients is a National Burn Care Guideline and is increasingly used to identify individuals most in need of support. It can also generate data that can inform our understanding of patient reported concerns following a burn injury. Method: As part of routine care, 461 patients admitted to a burns unit were screened soon after admission using a psychosocial screen designed by the service. The questionnaire included items on pre-existing social support, coping, emotional and psychological difficulties, as well as current trauma symptoms and current level of concern about changed appearance following the burn. Results: Overall, patients reported low levels of appearance concerns (mean 3.7/10) and trauma symptoms (18% reporting flashbacks) in the initial days following a burn injury. In those who did report concerns, there were some significant associations with demographic and other variables. Patients who experienced flashbacks were younger and had a larger total body surface area (TBSA) burn. Higher levels of appearance concern were associated with younger women, larger TBSA and facial burns. However, the relationships found were weak and frequently confounded by other factors. Conclusion: Overall, the findings indicate that initial trauma symptoms and appearance concerns are not inevitable in this group and there is no substitute for screening in identifying who is most at risk. PMID:29873338

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

Barriers to and enablers of diabetic retinopathy screening attendance: a systematic review of published and grey literature.

PubMed

Graham-Rowe, E; Lorencatto, F; Lawrenson, J G; Burr, J M; Grimshaw, J M; Ivers, N M; Presseau, J; Vale, L; Peto, T; Bunce, C; Francis, J J

2018-05-23

To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance. We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance. Sixty-nine primary studies were included. We identified six theoretical domains ['environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (50%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers. Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Optimization of protein buffer cocktails using Thermofluor.

PubMed

Reinhard, Linda; Mayerhofer, Hubert; Geerlof, Arie; Mueller-Dieckmann, Jochen; Weiss, Manfred S

2013-02-01

The stability and homogeneity of a protein sample is strongly influenced by the composition of the buffer that the protein is in. A quick and easy approach to identify a buffer composition which increases the stability and possibly the conformational homogeneity of a protein sample is the fluorescence-based thermal-shift assay (Thermofluor). Here, a novel 96-condition screen for Thermofluor experiments is presented which consists of buffer and additive parts. The buffer screen comprises 23 different buffers and the additive screen includes small-molecule additives such as salts and nucleotide analogues. The utilization of small-molecule components which increase the thermal stability of a protein sample frequently results in a protein preparation of higher quality and quantity and ultimately also increases the chances of the protein crystallizing.

Colonoscopy Screening in the US Astronaut Corps

NASA Technical Reports Server (NTRS)

Masterova, K.; Van Baalen, M.; Wear, M. L.; Murray, J.; Schaefer, C.

2016-01-01

Historically, colonoscopy screenings for astronauts have been conducted to ensure that astronauts are in good health for space missions. This data has been identified as being useful for determining appropriate occupational surveillance targets and requirements. Colonoscopies in the astronaut corps can be used for: (a) Assessing overall colon health, (b) A point of reference for future tests in current and former astronauts, (c) Following-up and tracking rates of colorectal cancer and polyps; and (d) Comparison to military and other terrestrial populations. In 2003, medical screening requirements for the active astronaut corps changed to require less frequent colonoscopies. Polyp removal during a colonoscopy is an intervention that prevents the polyp from potentially developing into cancer and decreases the individual's risk for colon cancer.

Regional Screening Levels Frequent Questions

EPA Pesticide Factsheets

Regional Screening Level RSL frequently asked question FAQ page provides risk assessors answers to common questions about the preliminary remediation goal PRG risk based concentration RBC and risk calculator for the assessment of human Health.

Regional Screening Levels Frequent Questions (November 2017)

EPA Pesticide Factsheets

Regional Screening Level RSL frequently asked question FAQ page provides risk assessors answers to common questions about the preliminary remediation goal PRG risk based concentration RBC and risk calculator for the assessment of human Health.

The Utility of the Modified Checklist for Autism in Toddlers in a Preschool-Age Special Education Sample

ERIC Educational Resources Information Center

Cogan-Ferchalk, JoAnna R.

2013-01-01

The number of young children with autism is ever-increasing, and school psychologists are more frequently required to identify these students. Valid screening tools are needed in order to focus school psychologists' time on those students in need of intensive evaluations in Early Intervention programs. The purpose of this study was to examine the…

Assertions of Japanese Websites for and Against Cancer Screening: a Text Mining Analysis

PubMed

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2017-04-01

Background: Cancer screening rates are lower in Japan than in Western countries such as the United States and the United Kingdom. While health professionals publish pro-cancer-screening messages online to encourage proactive seeking for screening, anti-screening activists use the same medium to warn readers against following guidelines. Contents of pro- and anti-cancer-screening sites may contribute to readers’ acceptance of one or the other position. We aimed to use a text-mining method to examine frequently appearing contents on sites for and against cancer screening. Methods: We conducted online searches in December 2016 using two major search engines in Japan (Google Japan and Yahoo! Japan). Targeted websites were classified as “pro”, “anti”, or “neutral” depending on their claims, with the author(s) classified as “health professional”, “mass media”, or “layperson”. Text-mining analyses were conducted, and statistical analysis was performed using the chi-square test. Results: Of the 169 websites analyzed, the top-three most frequently appearing content topics in pro sites were reducing mortality via cancer screening, benefits of early detection, and recommendations for obtaining detailed examination. The top three most frequent in anti-sites were harm from radiation exposure, non-efficacy of cancer screening, and lack of necessity of early detection. Anti-sites also frequently referred to a well-known Japanese radiologist, Makoto Kondo, who rejects the standard forms of cancer care. Conclusion: Our findings should enable authors of pro-cancer-screening sites to write to counter misleading anti-cancer-screening messages and facilitate dissemination of accurate information. Creative Commons Attribution License

Phage display screening without repetitious selection rounds.

PubMed

't Hoen, Peter A C; Jirka, Silvana M G; Ten Broeke, Bradley R; Schultes, Erik A; Aguilera, Begoña; Pang, Kar Him; Heemskerk, Hans; Aartsma-Rus, Annemieke; van Ommen, Gertjan J; den Dunnen, Johan T

2012-02-15

Phage display screenings are frequently employed to identify high-affinity peptides or antibodies. Although successful, phage display is a laborious technology and is notorious for identification of false positive hits. To accelerate and improve the selection process, we have employed Illumina next generation sequencing to deeply characterize the Ph.D.-7 M13 peptide phage display library before and after several rounds of biopanning on KS483 osteoblast cells. Sequencing of the naive library after one round of amplification in bacteria identifies propagation advantage as an important source of false positive hits. Most important, our data show that deep sequencing of the phage pool after a first round of biopanning is already sufficient to identify positive phages. Whereas traditional sequencing of a limited number of clones after one or two rounds of selection is uninformative, the required additional rounds of biopanning are associated with the risk of losing promising clones propagating slower than nonbinding phages. Confocal and live cell imaging confirms that our screen successfully selected a peptide with very high binding and uptake in osteoblasts. We conclude that next generation sequencing can significantly empower phage display screenings by accelerating the finding of specific binders and restraining the number of false positive hits. Copyright © 2011 Elsevier Inc. All rights reserved.

Barriers and facilitators to opportunistic chronic kidney disease screening by general practice nurses.

PubMed

Sinclair, Peter M; Day, Jenny; Levett-Jones, Tracy; Kable, Ashley

2017-10-01

Opportunistic screening in general practice (GP) is a cost-effective and viable approach to the early identification of chronic kidney disease (CKD). This study sought to identify the barriers and facilitators to CKD screening practices of GP nurses working in a regional area of New South Wales, Australia. An eight-item elicitation questionnaire informed by the Theory of Planned Behaviour was administered to a convenience sample of 26 GP nurses. Participants identified that the advantages of CKD screening were its early detection and treatment, the reduction of disease burden, and the opportunity to increase awareness and provide disease prevention education. These positive attitudinal beliefs were offset by negative beliefs about the impost of opportunistic screening on nursing time, particularly when there were other competing clinical priorities. Participants reported that practice doctors were wary of the financial costs associated with additional non-claimable services and believed that unfunded services, regardless of patient benefit, were difficult to justify in a private business environment. Screening was enabled in GP settings with existing screening protocols or initiatives, and when patients presented with known risk factors. Barriers to screening were more frequently described and illustrated a strong focus on financial aspects of GP. Without reimbursement through the Medicare Benefits Scheme, screening was not considered an economical use of nursing time. Other competing and billable clinical services took precedence. The findings of this study can be used to inform the development and evaluation of interventions that target opportunistic CKD screening in the GP setting. © 2016 Asian Pacific Society of Nephrology.

Predischarge screening for chronic obstructive pulmonary disease in patients with acute coronary syndrome and smoking history.

PubMed

Campo, Gianluca; Pavasini, Rita; Barbetta, Carlo; Maietti, Elisa; Mascetti, Susanna; Biscaglia, Simone; Zaraket, Fatima; Spitaleri, Giosafat; Gallo, Francesco; Tonet, Elisabetta; Papi, Alberto; Ferrari, Roberto; Contoli, Marco

2016-11-01

Several studies suggested that chronic obstructive pulmonary disease (COPD) is largely underdiagnosed in patients with acute coronary syndrome (ACS) contributing to further affect clinical outcome. Our aim was to validate a screening procedure to identify, in ACS patients, those with negligible risk of undiagnosed COPD. From December 2014 to August 2015, 169 ACS patients with smoking history underwent screening procedure. Screening procedure combined peak expiratory flow rate (PEFR, defined as positive if <80% of predicted) and respiratory health status questionnaire (RHSQ, defined as positive if >19.5 points). The screening was considered negative if both tests provided negative results, positive if both were positive, uncertain in presence of discrepancy. Spirometry was planned after 2months to identify or not the presence of irreversible airflow obstruction (undiagnosed COPD). The primary endpoint was the negative predictive value of screening for undiagnosed COPD. Overall, 137 (81%) patients received spirometry (final study population). Screening was negative, uncertain and positive in 58 (42%), 46 (34%) and 33 (24%) patients, respectively. We found undiagnosed COPD in 39 (29%) patients. Only 3 patients with negative screening showed undiagnosed COPD. Negative screening showed the best ability to discriminate patients without COPD (negative predictive value 95%). Two-month health status in patients with undiagnosed COPD was significantly poor. Undiagnosed COPD is relatively frequent in ACS patients with smoking history and a simple screening procedure including PEFR and RHSQ can be administered before hospital discharge to discriminate those at negligible risk of undiagnosed COPD (ClinicalTrials.gov, NCT02324660). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Leaflets and websites on colorectal cancer screening and their quality assessment from experts' views].

PubMed

Dreier, M; Borutta, B; Seidel, G; Münch, I; Töppich, J; Bitzer, E-M; Dierks, M-L; Walter, U

2014-03-01

In Germany, individuals who have statutory health insurance have free access to colorectal cancer (CRC) screening tests, and can choose between a fecal occult blood test and a screening colonoscopy. Evidence-based health information may support informed choices regarding whether or not to undergo CRC screening. The aim of this study was to assess whether the available German information materials on CRC screening meet evidence-based health information standards. A systematic search was made for print media and websites on CRC screening addressed to German people with average CRC risk (search period for print media August 2010, for websites January-March 2012). The identified information was assessed with a newly developed comprehensive list of criteria. In all, 41 print media, including 28 flyers and 13 brochures, and 36 websites were identified and assessed. These materials reported more often the benefits than the risks of CRC screening, and quantified presentations of benefits and risks were less frequently given. Most of the materials called for participation and did not indicate the option to decide whether or not to attend CRC screening. This bias in favor of screening was increased by fear-provoking or downplayed wording. Most materials included false and misleading information. The requirements for evidence-based patient information were currently not met by most of the leaflets and websites in Germany. Feedback was given to the producers of the leaflets including a discussion of the findings. The results may be used to revise existing leaflets or to develop new health information on CRC screening.

Reviewing Large LAMA2 Deletions and Duplications in Congenital Muscular Dystrophy Patients.

PubMed

Oliveira, Jorge; Gonçalves, Ana; Oliveira, Márcia E; Fineza, Isabel; Pavanello, Rita C M; Vainzof, Mariz; Bronze-da-Rocha, Elsa; Santos, Rosário; Sousa, Mário

2014-01-01

Congenital muscular dystrophy (CMD) type 1A (MDC1A) is caused by recessive mutations in laminin-α2 (LAMA2) gene. Laminin-211, a heterotrimeric glycoprotein that contains the α2 chain, is crucial for muscle stability establishing a bond between the sarcolemma and the extracellular matrix. More than 215 mutations are listed in the locus specific database (LSDB) for LAMA2 gene (May 2014). A limited number of large deletions/duplications have been reported in LAMA2. Our main objective was the identification of additional large rearrangements in LAMA2 found in CMD patients and a systematic review of cases in the literature and LSDB. In four of the fifty-two patients studied over the last 10 years, only one heterozygous mutation was identified, after sequencing and screening for a frequent LAMA2 deletion. Initial screening of large mutations was performed by multiplex ligation-dependent probe application (MLPA). Further characterization implied several techniques: long-range PCR, cDNA and Southern-blot analysis. Three novel large deletions in LAMA2 and the first pathogenic large duplication were successfully identified, allowing a definitive molecular diagnosis, carrier screening and prenatal diagnosis. A total of fifteen deletions and two duplications previously reported were also reviewed. Two possible mutational "hotspots" for deletions may exist, the first encompassing exons 3 and 4 and second in the 3' region (exons 56 to 65) of LAMA2. Our findings show that this type of mutation is fairly frequent (18.4% of mutated alleles) and is underestimated in the literature. It is important to include the screening of large deletions/duplications as part of the genetic diagnosis strategy.

Falls risk assessment in older patients in hospital.

PubMed

Matarese, Maria; Ivziku, Dhurata

2016-07-27

Falls are the most frequent adverse event reported in hospitals, usually affecting older patients. All hospitals in NHS organisations develop risk prevention policies that include falls risk assessment. Falls risk assessment involves the use of risk screening tools, aimed at identifying patients at increased risk of falls, and risk assessment tools, which identify a patient's risk factors for falls. Various risk screening tools have been used in clinical practice, but no single tool is able to identify all patients at risk of falls or to accurately exclude all those who are not at risk of falls. Guidelines recommend that patients aged 65 years and over who are admitted to hospital should be considered at high risk of falls and that a multifactorial falls risk assessment should be performed. Therefore, falls risk assessment tools should be used to identify the risk factors for each inpatient aged 65 years or over, in order to determine the most appropriate care plan for falls prevention and to maximise patient mobility and independence.

Screening for disability in the inner city.

PubMed Central

Patrick, D L; Darby, S C; Green, S; Horton, G; Locker, D; Wiggins, R D

1981-01-01

A 10% sample of private households on the electoral register of the London borough of Lambeth was screened for disable persons aged 16 and over, using a postal questionnaire. After three mailings and individual follow-up of non-responders, 87% of the sample households returned questionnaires. Disability was defined in the screening questionnaire as functional limitations or activity restrictions consequent upon disease or impairment. The overall point prevalence of disability was estimated at 15.4% and the most frequently reported impairments were those of the sense organs, bones, central nervous, circulatory, and respiratory systems. Hearing difficulties were the single most frequently reported functional limitation. A log-linear modelling procedure identified age, marital status, and working status as the factors most strongly associated with disability for both men and women. In addition, men aged 50-64 and not working, and men in manual occupations and living alone, were more likely to report disability. These findings indicate that some population groups are disable by functional limitations and activity restrictions not included in office criteria of identification and assessment. These criteria might be broadened, and serves planned for those population groups with higher rates of reported disability. PMID:6455485

Measuring Quality Gaps in TB Screening in South Africa Using Standardised Patient Analysis.

PubMed

Christian, Carmen S; Gerdtham, Ulf-G; Hompashe, Dumisani; Smith, Anja; Burger, Ronelle

2018-04-12

This is the first multi-district Standardised Patient (SP) study in South Africa. It measures the quality of TB screening at primary healthcare (PHC) facilities. We hypothesise that TB screening protocols and best practices are poorly adhered to at the PHC level. The SP method allows researchers to observe how healthcare providers identify, test and advise presumptive TB patients, and whether this aligns with clinical protocols and best practice. The study was conducted at PHC facilities in two provinces and 143 interactions at 39 facilities were analysed. Only 43% of interactions resulted in SPs receiving a TB sputum test and being offered an HIV test. TB sputum tests were conducted routinely (84%) while HIV tests were offered less frequently (47%). Nurses frequently neglected to ask SPs whether their household contacts had confirmed TB (54%). Antibiotics were prescribed without taking temperatures in 8% of cases. The importance of returning to the facility to receive TB test results was only explained in 28%. The SP method has highlighted gaps in clinical practice, signalling missed opportunities. Early detection of sub-optimal TB care is instrumental in decreasing TB-related morbidity and mortality. The findings provide the rationale for further quality improvement work in TB management.

Screening tools for the identification of dementia for adults with age-related acquired hearing or vision impairment: a scoping review.

PubMed

Pye, Annie; Charalambous, Anna Pavlina; Leroi, Iracema; Thodi, Chrysoulla; Dawes, Piers

2017-11-01

Cognitive screening tests frequently rely on items being correctly heard or seen. We aimed to identify, describe, and evaluate the adaptation, validity, and availability of cognitive screening and assessment tools for dementia which have been developed or adapted for adults with acquired hearing and/or vision impairment. Electronic databases were searched using subject terms "hearing disorders" OR "vision disorders" AND "cognitive assessment," supplemented by exploring reference lists of included papers and via consultation with health professionals to identify additional literature. 1,551 papers were identified, of which 13 met inclusion criteria. Four papers related to tests adapted for hearing impairment; 11 papers related to tests adapted for vision impairment. Frequently adapted tests were the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA). Adaptations for hearing impairment involved deleting or creating written versions for hearing-dependent items. Adaptations for vision impairment involved deleting vision-dependent items or spoken/tactile versions of visual tasks. No study reported validity of the test in relation to detection of dementia in people with hearing/vision impairment. Item deletion had a negative impact on the psychometric properties of the test. While attempts have been made to adapt cognitive tests for people with acquired hearing and/or vision impairment, the primary limitation of these adaptations is that their validity in accurately detecting dementia among those with acquired hearing or vision impairment is yet to be established. It is likely that the sensitivity and specificity of the adapted versions are poorer than the original, especially if the adaptation involved item deletion. One solution would involve item substitution in an alternative sensory modality followed by re-validation of the adapted test.

Early detection and management of pulmonary arterial hypertension.

PubMed

Humbert, Marc; Gerry Coghlan, J; Khanna, Dinesh

2012-12-01

The long-term prognosis for patients with pulmonary arterial hypertension (PAH) remains poor, despite advances in treatment options that have been made in the past few decades. Recent evidence suggests that World Health Organization functional class I or II patients have significantly better long-term survival rates than patients in higher functional classes, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programmes play an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH (i.e. those with systemic sclerosis or sickle cell disease), although current guidelines only recommend annual echocardiographic screening in symptomatic patients. This article reviews the currently available screening programmes, including their limitations, and describes alternative screening approaches that may identify more effectively those patients who require right heart catheterisation for a definitive PAH diagnosis.

Prevention and anthropology.

PubMed

Jopp, Eilin; Scheffler, Christiane; Hermanussen, Michael

2014-01-01

Screening is an important issue in medicine and is used to early identify unrecognised diseases in persons who are apparently in good health. Screening strongly relies on the concept of "normal values". Normal values are defined as values that are frequently observed in a population and usually range within certain statistical limits. Screening for obesity should start early as the prevalence of obesity consolidates already at early school age. Though widely practiced, measuring BMI is not the ultimate solution for detecting obesity. Children with high BMI may be "robust" in skeletal dimensions. Assessing skeletal robustness and in particularly assessing developmental tempo in adolescents are also important issues in health screening. Yet, in spite of the necessity of screening investigations, appropriate reference values are often missing. Meanwhile, new concepts of growth diagrams have been developed. Stage line diagrams are useful for tracking developmental processes over time. Functional data analyses have efficiently been used for analysing longitudinal growth in height and assessing the tempo of maturation. Convenient low-cost statistics have also been developed for generating synthetic national references.

Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

PubMed

Koike-Yusa, Hiroko; Li, Yilong; Tan, E-Pien; Velasco-Herrera, Martin Del Castillo; Yusa, Kosuke

2014-03-01

Identification of genes influencing a phenotype of interest is frequently achieved through genetic screening by RNA interference (RNAi) or knockouts. However, RNAi may only achieve partial depletion of gene activity, and knockout-based screens are difficult in diploid mammalian cells. Here we took advantage of the efficiency and high throughput of genome editing based on type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems to introduce genome-wide targeted mutations in mouse embryonic stem cells (ESCs). We designed 87,897 guide RNAs (gRNAs) targeting 19,150 mouse protein-coding genes and used a lentiviral vector to express these gRNAs in ESCs that constitutively express Cas9. Screening the resulting ESC mutant libraries for resistance to either Clostridium septicum alpha-toxin or 6-thioguanine identified 27 known and 4 previously unknown genes implicated in these phenotypes. Our results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system.

Diverse microRNAs with convergent functions regulate tumorigenesis.

PubMed

Zhu, Min-Yan; Zhang, Wei; Yang, Tao

2016-02-01

MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-β, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks.

Biomedical Informatics Approaches to Identifying Drug-Drug Interactions: Application to Insulin Secretagogues

PubMed Central

Han, Xu; Chiang, ChienWei; Leonard, Charles E.; Bilker, Warren B.; Brensinger, Colleen M.; Li, Lang; Hennessy, Sean

2017-01-01

Background Drug-drug interactions with insulin secretagogues are associated with increased risk of serious hypoglycemia in patients with type 2 diabetes. We aimed to systematically screen for drugs that interact with the five most commonly used secretagogues―glipizide, glyburide, glimepiride, repaglinide, and nateglinide―to cause serious hypoglycemia. Methods We screened 400 drugs frequently co-prescribed with the secretagogues as candidate interacting precipitants. We first predicted the drug–drug interaction potential based on the pharmacokinetics of each secretagogue–precipitant pair. We then performed pharmacoepidemiologic screening for each secretagogue of interest, and for metformin as a negative control, using an administrative claims database and the self-controlled case series design. The overall rate ratios (RRs) and those for four predefined risk periods were estimated using Poisson regression. The RRs were adjusted for multiple estimation using semi-Bayes method, and then adjusted for metformin results to distinguish native effects of the precipitant from a drug–drug interaction. Results We predicted 34 pharmacokinetic drug–drug interactions with the secretagogues, nine moderate and 25 weak. There were 140 and 61 secretagogue–precipitant pairs associated with increased rates of serious hypoglycemia before and after the metformin adjustment, respectively. The results from pharmacokinetic prediction correlated poorly with those from pharmacoepidemiologic screening. Conclusions The self-controlled case series design has the potential to be widely applicable to screening for drug–drug interactions that lead to adverse outcomes identifiable in healthcare databases. Coupling pharmacokinetic prediction with pharmacoepidemiologic screening did not notably improve the ability to identify drug–drug interactions in this case. PMID:28169935

Detection of large scale 3' deletions in the PMS2 gene amongst Colon-CFR participants: have we been missing anything?

PubMed

Clendenning, Mark; Walsh, Michael D; Gelpi, Judith Balmana; Thibodeau, Stephen N; Lindor, Noralane; Potter, John D; Newcomb, Polly; LeMarchand, Loic; Haile, Robert; Gallinger, Steve; Hopper, John L; Jenkins, Mark A; Rosty, Christophe; Young, Joanne P; Buchanan, Daniel D

2013-09-01

Current screening practices have been able to identify PMS2 mutations in 78 % of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3' end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22 % (n = 16) of CRC-affected probands for mutations in the 3' end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3' deletions in PMS2 are not a frequent occurrence in such families.

Is unhealthy substance use associated with failure to receive cancer screening and flu vaccination? A retrospective cross-sectional study

PubMed Central

Kim, Theresa W; Alford, Daniel P; Cabral, Howard; Saitz, Richard; Samet, Jeffrey H

2011-01-01

Objective To compare cancer screening and flu vaccination among persons with and without unhealthy substance use. Design The authors analysed data from 4804 women eligible for mammograms, 4414 eligible for Papanicolou (Pap) smears, 7008 persons eligible for colorectal cancer (CRC) screening and 7017 persons eligible for flu vaccination. All patients were screened for unhealthy substance use. The main outcome was completion of cancer screening and flu vaccination. Results Among the 9995 patients eligible for one or more of the preventive services of interest, 10% screened positive for unhealthy substance use. Compared with women without unhealthy substance use, women with unhealthy substance use received mammograms less frequently (75.4% vs 83.8%; p<0.0001), but Pap smears no less frequently (77.9% vs 78.1%). Persons with unhealthy substance use received CRC screening no less frequently (61.7% vs 63.4%), yet received flu vaccination less frequently (44.7% vs 50.4%; p=0.01). In multivariable analyses, women with unhealthy substance use were less likely to receive mammograms (adjusted odds ratio 0.68; 95% CI 0.52 to 0.89), and persons with unhealthy substance use were less likely to receive flu vaccination (adjusted odds ratio 0.81; 95% CI 0.67 to 0.97). Conclusions Unhealthy substance use is a risk factor for not receiving all appropriate preventive health services. PMID:22021737

Implementation of newborn screening for cystic fibrosis in Norway. Results from the first three years.

PubMed

Lundman, Emma; Gaup, H Junita; Bakkeheim, Egil; Olafsdottir, Edda J; Rootwelt, Terje; Storrøsten, Olav Trond; Pettersen, Rolf D

2016-05-01

Norway introduced newborn screening for cystic fibrosis (CF) March 1, 2012. We present results from the first three years of the national newborn CF screening program. Positive primary screening of immunoreactive trypsinogen (IRT) was followed by DNA testing of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infants with two CFTR mutations were reported for diagnostic follow-up. Of 181,859 infants tested, 1454 samples (0.80%) were assessed for CFTR mutations. Forty children (1:4546) had two CFTR mutations, of which only 21 (1:8660) were confirmed to have a CF diagnosis. The CFTR mutations differed from previously clinically diagnosed CF patients, and p.R117H outnumbered p.F508del as the most frequent mutation. One child with a negative IRT screening test was later clinically diagnosed with CF. The CF screening program identified fewer children with a conclusive CF diagnosis than expected. Our data suggest a revision of the IRT/DNA protocol. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Prevalence of HIV in pregnant women identified with a risk factor at a tertiary care hospital.

PubMed

Mahmud, Ghazala; Abbas, Shazra

2009-01-01

HIV is an epidemic quite unlike any other, combining the problems of a lifelong medical disease with immense social, psychological, economic and public health consequences. Since we are living in a global village where human interactions has become fast and frequent, diseases like HIV are no more alien to us. HIV/AIDS in Pakistan is slowly gaining recognition as a public health issue of great importance. Objectives of this study were to determine the prevalence of HIV in pregnant women identified with a high risk factor/behaviour at a tertiary care hospital. It is a Descriptive study. All pregnant women attending antenatal booking clinic were assessed via a pre-designed 'Risk assessment questionnaire'. Women identified with a risk factor were offered HIV Rapid screening test (Capillus HIV1/2). Positive (reactive) results on screening test were confirmed with ELISA. During the study period (March 2007-May 2008), out of 5263 antenatal bookings 785 (14%) women were identified with a risk factor. HIV screening test was done in 779 (99%), and 6 women refused testing. Three women (0.3%) were found positive (reactive) on screening. Two out of 3 women were confirmed positive (0.2%) on ELISA. Husbands of both women were tested and one found positive (migrant from Dubai). Second women had history of blood transfusion. Her husband was HIV negative. During the study period, in addition to 2 pregnant women diagnosed as HIV positive through ANC risk screening, 6 confirmed HIV positive women, found pregnant were referred from 'HIV Treatment Centre', Pakistan Institute of Medical Sciences (PIMS) to Prevention of Parent to Child Transmission (PPTCT) centre for obstetric care. Spouses of 5 out of 6 had history of working abroad and extramarital sexual relationships. All positive (8) women were referred to PPTCT centre for further management. A simple 'Risk Assessment Questionnaire' can help us in identifying women who need HIV screening. Sexual transmission still remains the commonest cause of HIV transmission.

Breast Cancer Screening Programmes across the WHO European Region: Differences among Countries Based on National Income Level.

PubMed

Altobelli, Emma; Rapacchietta, Leonardo; Angeletti, Paolo Matteo; Barbante, Luca; Profeta, Filippo Valerio; Fagnano, Roberto

2017-04-23

Breast cancer (BC) is the most frequent tumour affecting women all over the world. In low- and middle-income countries, where its incidence is expected to rise further, BC seems set to become a public health emergency. The aim of the present study is to provide a systematic review of current BC screening programmes in WHO European Region to identify possible patterns. Multiple correspondence analysis was performed to evaluate the association among: measures of occurrence; GNI level; type of BC screening programme; organization of public information and awareness campaigns regarding primary prevention of modifiable risk factors; type of BC screening services; year of screening institution; screening coverage and data quality. A key difference between High Income (HI) and Low and Middle Income (LMI) States, emerging from the present data, is that in the former screening programmes are well organized, with approved screening centres, the presence of mobile units to increase coverage, the offer of screening tests free of charge; the fairly high quality of occurrence data based on high-quality sources, and the adoption of accurate methods to estimate incidence and mortality. In conclusion, the governments of LMI countries should allocate sufficient resources to increase screening participation and they should improve the accuracy of incidence and mortality rates.

Less screen time and more frequent vigorous physical activity is associated with lower risk of reporting negative mental health symptoms among Icelandic adolescents.

PubMed

Hrafnkelsdottir, Soffia M; Brychta, Robert J; Rognvaldsdottir, Vaka; Gestsdottir, Sunna; Chen, Kong Y; Johannsson, Erlingur; Guðmundsdottir, Sigridur L; Arngrimsson, Sigurbjorn A

2018-01-01

Few studies have explored the potential interrelated associations of screen time and physical activity with mental health in youth, particularly using objective methods. We examined cross-sectional associations of these variables among Icelandic adolescents, using objective and subjective measurements of physical activity. Data were collected in the spring of 2015 from 315 tenth grade students (mean age 15.8 years) in six elementary schools in metropolitan Reykjavík, Iceland. Participants reported, via questionnaire, on demographics, weekly frequency of vigorous physical activity, daily hours of screen time and mental health status (symptoms of depression, anxiety and somatic complaints, self-esteem and life satisfaction). Total physical activity was measured over one week with wrist-worn accelerometers. Body composition was determined by DXA-scanning. Poisson regression analysis was used to explore independent and interactive associations of screen time and physical activity with mental health variables, adjusting for gender, body fat percentage and maternal education. Less screen time (below the group median of 5.3 h/day) and more frequent vigorous physical activity (≥4x/week) were each associated with reporting fewer symptoms of depression, anxiety, low self-esteem, and life dissatisfaction. No significant associations were observed between objectively measured physical activity and mental health outcomes. Interactive regression analysis showed that the group reporting both less screen time and more frequent vigorous physical activity had the lowest risk of reporting symptoms of depression, anxiety, low self-esteem, and life dissatisfaction. Reports of less screen time and more frequent vigorous physical activity were associated with lower risk of reporting mental health problems among Icelandic adolescents. Those who reported a combination of engaging in less screen time and more frequent vigorous physical activity had the lowest risk, suggesting a synergistic relationship between the two behaviors on mental health outcomes. Our results support guiding youth towards more active and less sedentary/screen-based lifestyle.

Unsheltered Homelessness Among Veterans: Correlates and Profiles.

PubMed

Byrne, Thomas; Montgomery, Ann Elizabeth; Fargo, Jamison D

2016-02-01

We identified correlates of unsheltered status among Veterans experiencing homelessness and described distinct subgroups within the unsheltered homeless Veteran population using data from a screening instrument for homelessness that is administered to all Veterans accessing outpatient care at a Veterans Health Administration (VHA) facility. Correlates of unsheltered homelessness included male gender, white race, older age, lower levels of VHA eligibility, substance use disorders, frequent use of VHA inpatient and infrequent use of VHA outpatient services, and residing in the West. We identified six distinct subgroups of unsheltered Veterans; the tri-morbid frequent users represented the highest need group, but the largest group was comprised of Veterans who made highly infrequent use of VHA healthcare services. Differences between sheltered and unsheltered Veterans and heterogeneity within the unsheltered Veteran population should be considered in targeting housing and other interventions.

Challenges with access to healthcare from the perspective of patients living with HIV: a scoping review & framework synthesis.

PubMed

Asghari, Shabnam; Hurd, Jillian; Marshall, Zack; Maybank, Allison; Hesselbarth, Lydia; Hurley, Oliver; Farrell, Alison; Kendall, Claire E; Rourke, Sean B; Becker, Marissa; Johnston, Sharon; Lundrigan, Phil; Rosenes, Ron; Bibeau, Christine; Liddy, Clare

2018-08-01

Accessing healthcare can be difficult but the barriers multiply for people living with HIV (PLHIV). To improve access and the health of PLHIV, we must consider their perspectives and use them to inform standard practice. A better understanding of the current literature related to healthcare access from the perspective of PLHIV, can help to identify evidence gaps and highlight research priorities and opportunities. To identify relevant peer-reviewed publications, search strategies were employed. Electronic and grey literature databases were explored. Articles were screened based on their title and abstract and those that met the screening criteria, were reviewed in full. Data analysis was conducted using a collaborative approach that included knowledge user consultation. Initial concepts were extracted, summarized and through framework synthesis, developed into emerging and final themes. From 20,678 articles, 326 articles met the initial screening criteria and 64 were reviewed in full. The final themes identified, in order of most to least frequent were: Acceptability, Availability, Accessibility, Affordability, Other Barriers, Communication, Satisfaction, Accommodation, Preferences and Equity in Access. The most frequently discussed concepts related to negative interactions with staff, followed by long wait times, limited household resources or inability to pay fees, and fear of one's serostatus being disclosed. Knowledge users were in agreement with the categorization of initial concepts and final themes; however, some gaps in the literature were identified. Specific changes are critical to improving access to healthcare for PLHIV. These include improving availability by ensuring staff and healthcare professionals have proper training, cultivating acceptability and reducing stigma through improving HIV awareness, increasing accessibility through increased HIV information for PLHIV and improved dissemination of this information to increase patient knowledge and health awareness. Finally, ensuring proper protocols are implemented and followed to guarantee patient confidentiality and overall satisfaction with healthcare services are recommended.

Older Adults’ Views and Communication Preferences About Cancer Screening Cessation

PubMed Central

Schoenborn, Nancy L.; Lee, Kimberley; Pollack, Craig E.; Armacost, Karen; Dy, Sydney M.; Bridges, John F. P.; Xue, Qian-Li; Wolff, Antonio C.; Boyd, Cynthia

2017-01-01

IMPORTANCE Older adults with limited life expectancy are frequently screened for cancer even though it exposes them to risks of screening with minimal benefit. Patient preferences may be an important contributor to continued screening. OBJECTIVE To examine older adults’ views on the decision to stop cancer screening when life expectancy is limited and to identify older adults’ preferences for how clinicians should communicate recommendations to cease cancer screening. DESIGN, SETTING, AND PARTICIPANTS In this semistructured interview study, we interviewed 40 community-dwelling older adults (≥ 65 years) recruited at 4 clinical programs affiliated with an urban academic medical center. MAIN OUTCOMES AND MEASURE We transcribed the audio recorded discussions and analyzed the transcripts using standard techniques of qualitative content analysis to identify major themes and subthemes. RESULTS The participants’ average age was 75.7 years. Twenty-three participants (57.5%) were female; 25 (62.5%) were white. Estimated life expectancy was less than 10 years for 19 participants (47.5%). We identified 3 key themes. First, participants were amenable to stopping cancer screening, especially in the context of a trusting relationship with their clinician. Second, although many participants supported using age and health status to individualize the screening decision, they did not often understand the role of life expectancy. All except 2 participants objected to a Choosing Wisely statement about not recommending cancer screening in those with limited life expectancy, often believing that clinicians cannot accurately predict life expectancy. Third, participants preferred that clinicians explain a recommendation to stop screening by incorporating individual health status but were divided on whether life expectancy should be mentioned. Specific wording of life expectancy was important; many felt the language of “you may not live long enough to benefit from this test” was unnecessarily harsh compared with the more positive messaging of “this test would not help you live longer.” CONCLUSIONS AND RELEVANCE Although research and clinical practice guidelines recommend using life expectancy to inform cancer screening, older adults may not consider life expectancy important in screening and may not prefer to hear about life expectancy when discussing screening. The described communication preferences can help inform future screening discussions. Better delineating patient-centered approaches to discuss screening cessation is an important step toward optimizing cancer screening in older adults. PMID:28604917

Hepatitis C screening trends in a large integrated health system

PubMed Central

Linas, Benjamin P.; Hu, Haihong; Barter, Devra M.; Horberg, Michael

2014-01-01

Background As new hepatitis C virus (HCV) therapies emerge, only 1–12% of individuals are screened in the U.S. for HCV infection. Presently, HCV screening trends are unknown. Methods We utilized the Kaiser Permanente Mid-Atlantic States’ (KPMAS) data repository to investigate HCV antibody screening between 1/1/2003 and 12/31/2012. We identified the proportion screened for HCV and 5-year cumulative incidence of screening, the screening positivity rate, the provider types performing HCV screening, patient-level factors associated with being screened, and trends in screening over time. Results 444,594 patients met the inclusion criteria. Overall, 15.8% of the cohort was ever screened for HCV. Adult primary care and obstetrics and gynecology providers performed 75.9% of all screening. The overall test positivity rate was 3.8%. Screening was more frequent in younger age groups (p<0.0001) and those with a documented history of illicit drug use (p<0.0001). Patients with missing drug use history (46.7%) were least likely to be screened (p<0.0001). While the rate of HCV screening increased in the later years of the study, among those enrolled in KPMAS 2009–2012, only 11.8% were screened by the end of follow-up. Conclusion Screening for HCV is increasing, but remains incomplete. Targeting screening to those with a history of injection drug will not likely expand screening, as nearly half of patients have no documented drug use history. Routine screening is likely the most effective approach to expand HCV screening. PMID:24486288

Hepatitis C screening trends in a large integrated health system.

PubMed

Linas, Benjamin P; Hu, Haihong; Barter, Devra M; Horberg, Michael

2014-05-01

As new hepatitis C virus (HCV) therapies emerge, only 1%-12% of individuals are screened in the US for HCV infection. Presently, HCV screening trends are unknown. We utilized the Kaiser Permanente Mid-Atlantic States' (KPMAS) data repository to investigate HCV antibody screening between January 1, 2003 and December 31, 2012. We identified the proportion screened for HCV and 5-year cumulative incidence of screening, the screening positivity rate, the provider types performing HCV screening, patient-level factors associated with being screened, and trends in screening over time. There were 444,594 patients who met the inclusion criteria. Overall, 15.8% of the cohort was ever screened for HCV. Adult primary care and obstetrics and gynecology providers performed 75.9% of all screening. The overall test positivity rate was 3.8%. Screening was more frequent in younger age groups (P <.0001) and those with a documented history of illicit drug use (P <.0001). Patients with missing drug use history (46.7%) were least likely to be screened (P <.0001). While the rate of HCV screening increased in the later years of the study among those enrolled in KPMAS 2009-2012, only 11.8% were screened by the end of follow-up. Screening for HCV is increasing but remains incomplete. Targeting screening to those with a history of injection drug will not likely expand screening, as nearly half of patients have no documented drug use history. Routine screening is likely the most effective approach to expand HCV screening. Copyright © 2014. Published by Elsevier Inc.

Establishment of a luciferase assay-based screening system: Fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Lei; Sasai, Ken; Akagi, Tsuyoshi

2008-08-29

The AKT pathway is frequently activated in glioblastoma, and as such, inhibitors of this pathway could prove very useful as anti-glioblastoma therapies. Here we established immortalized astrocytes expressing Renilla luciferase as well as those expressing both an active form of AKT and firefly luciferase. Since both luciferase activities represent the numbers of corresponding cell lines, novel inhibitors of the AKT pathway can be identified by treating co-cultures containing the two types of luciferase-expressing cells with individual compounds. Indeed, such a screening system succeeded in identifying fumitremorgin C as an efficient inhibitor of the AKT pathway, which was further confirmed bymore » the ability of fumitremorgin C to selectively inhibit the growth of immortalized astrocytes expressing an active form of AKT. The present study proposes a broadly applicable approach for identifying therapeutic agents that target the pathways and/or molecules responsible for cancer development.« less

Prostate and Colon Cancer Screening Messages in Popular Magazines

PubMed Central

Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

2004-01-01

OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

Synthetic Lethal Screens Identify Vulnerabilities in GPCR Signaling and Cytoskeletal Organization in E-Cadherin-Deficient Cells.

PubMed

Telford, Bryony J; Chen, Augustine; Beetham, Henry; Frick, James; Brew, Tom P; Gould, Cathryn M; Single, Andrew; Godwin, Tanis; Simpson, Kaylene J; Guilford, Parry

2015-05-01

The CDH1 gene, which encodes the cell-to-cell adhesion protein E-cadherin, is frequently mutated in lobular breast cancer (LBC) and diffuse gastric cancer (DGC). However, because E-cadherin is a tumor suppressor protein and lost from the cancer cell, it is not a conventional drug target. To overcome this, we have taken a synthetic lethal approach to determine whether the loss of E-cadherin creates druggable vulnerabilities. We first conducted a genome-wide siRNA screen of isogenic MCF10A cells with and without CDH1 expression. Gene ontology analysis demonstrated that G-protein-coupled receptor (GPCR) signaling proteins were highly enriched among the synthetic lethal candidates. Diverse families of cytoskeletal proteins were also frequently represented. These broad classes of E-cadherin synthetic lethal hits were validated using both lentiviral-mediated shRNA knockdown and specific antagonists, including the JAK inhibitor LY2784544, Pertussis toxin, and the aurora kinase inhibitors alisertib and danusertib. Next, we conducted a 4,057 known drug screen and time course studies on the CDH1 isogenic MCF10A cell lines and identified additional drug classes with linkages to GPCR signaling and cytoskeletal function that showed evidence of E-cadherin synthetic lethality. These included multiple histone deacetylase inhibitors, including vorinostat and entinostat, PI3K inhibitors, and the tyrosine kinase inhibitors crizotinib and saracatinib. Together, these results demonstrate that E-cadherin loss creates druggable vulnerabilities that have the potential to improve the management of both sporadic and familial LBC and DGC. ©2015 American Association for Cancer Research.

A genome-wide map of hyper-edited RNA reveals numerous new sites.

PubMed

Porath, Hagit T; Carmi, Shai; Levanon, Erez Y

2014-08-27

Adenosine-to-inosine editing is one of the most frequent post-transcriptional modifications, manifested as A-to-G mismatches when comparing RNA sequences with their source DNA. Recently, a number of RNA-seq data sets have been screened for the presence of A-to-G editing, and hundreds of thousands of editing sites identified. Here we show that existing screens missed the majority of sites by ignoring reads with excessive ('hyper') editing that do not easily align to the genome. We show that careful alignment and examination of the unmapped reads in RNA-seq studies reveal numerous new sites, usually many more than originally discovered, and in precisely those regions that are most heavily edited. Specifically, we discover 327,096 new editing sites in the heavily studied Illumina Human BodyMap data and more than double the number of detected sites in several published screens. We also identify thousands of new sites in mouse, rat, opossum and fly. Our results establish that hyper-editing events account for the majority of editing sites.

Early microbial colonization of cystic fibrosis patients identified by neonatal screening, with emphasis on Staphylococcus aureus.

PubMed

Souza, Helena A P H M; Nogueira, Keite S; Matos, Adriana P; Vieira, Ricardo P; Riedi, Carlos A; Rosário, Nelson A; Telles, Flávio Q; Costa, Libera M Dalla

2006-01-01

To assess bacterial colonization prospectively in patients with cystic fibrosis identified by neonatal screening. To assess susceptibility to antimicrobials and to perform the molecular typing of Staphylococcus aureus strains isolated from the oropharynx of patients during the study. Twenty-five cystic fibrosis patients receiving regular treatment at the Cystic Fibrosis Outpatient Clinic of Hospital de Clínicas of Universidade Federal do Paraná, Brazil, were included in the study. All patients were identified by trypsin-like immunoreactivity and their diagnosis was confirmed by two or more sweat tests. Oropharyngeal swabs were collected and cultured according to routine methods; bacterial colonies were phenotypically identified and their susceptibility to antimicrobials was tested. S. aureus isolates were submitted to molecular typing using pulsed-field gel electrophoresis. Out of 234 oropharyngeal swabs, S. aureus was the most frequently isolated strain (76% of patients, 42% of swabs), followed by Pseudomonas aeruginosa (36% of patients, 16% of swabs) and Haemophilus spp. (76% of patients; 19% of swabs). Seventy-three isolates were obtained from 19 patients colonized with S. aureus, of which 18 were oxacillin-resistant (24.6%), isolated from two patients, with the same electrophoretic profiles as that of the Brazilian clone. The remaining oxacillin-sensitive isolates were distributed into 18 electrophoretic profiles. There was higher prevalence of S. aureus, with earlier isolation than other pathogens. Multi-sensitive isolates were distributed into different clones, characterizing non-transmissibility among community-acquired strains. The isolated oxacillin-resistant S. aureus showed identical electrophoretic profiles, probably acquired in hospital. P. aeruginosa was not so frequent in the studied population.

Cost-Effectiveness of Enhanced Syphilis Screening among HIV-Positive Men Who Have Sex with Men: A Microsimulation Model

PubMed Central

Tuite, Ashleigh R.; Burchell, Ann N.; Fisman, David N.

2014-01-01

Background Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population. Purpose We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care. Methods We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer. Results Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV. Conclusions We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this group (i.e., for viral load monitoring) makes intensification of syphilis screening appear readily practicable. PMID:24983455

Challenges and Opportunities to Improve Cervical Cancer Screening Rates in US Health Centers through Patient-Centered Medical Home Transformation

PubMed Central

Makaroff, Laura; Chung, Michelle; Lin, Sue C.

2015-01-01

Over the last 50 years, the incidence of cervical cancer has dramatically decreased. However, health disparities in cervical cancer screening (CCS) persist for women from racial and ethnic minorities and those residing in rural and poor communities. For more than 45 years, federally funded health centers (HCs) have been providing comprehensive, culturally competent, and quality primary health care services to medically underserved communities and vulnerable populations. To enhance the quality of care and to ensure more women served at HCs are screened for cervical cancer, over eight HCs received funding to support patient-centered medical home (PCMH) transformation with goals to increase CCS rates. The study conducted a qualitative analysis using Atlas.ti software to describe the barriers and challenges to CCS and PCMH transformation, to identify potential solutions and opportunities, and to examine patterns in barriers and solutions proposed by HCs. Interrater reliability was assessed using Cohen's Kappa. The findings indicated that HCs more frequently described patient-level barriers to CCS, including demographic, cultural, and health belief/behavior factors. System-level barriers were the next commonly cited, particularly failure to use the full capability of electronic medical records (EMRs) and problems coordinating with external labs or providers. Provider-level barriers were least frequently cited. PMID:25685561

Molecular scaffold analysis of natural products databases in the public domain.

PubMed

Yongye, Austin B; Waddell, Jacob; Medina-Franco, José L

2012-11-01

Natural products represent important sources of bioactive compounds in drug discovery efforts. In this work, we compiled five natural products databases available in the public domain and performed a comprehensive chemoinformatic analysis focused on the content and diversity of the scaffolds with an overview of the diversity based on molecular fingerprints. The natural products databases were compared with each other and with a set of molecules obtained from in-house combinatorial libraries, and with a general screening commercial library. It was found that publicly available natural products databases have different scaffold diversity. In contrast to the common concept that larger libraries have the largest scaffold diversity, the largest natural products collection analyzed in this work was not the most diverse. The general screening library showed, overall, the highest scaffold diversity. However, considering the most frequent scaffolds, the general reference library was the least diverse. In general, natural products databases in the public domain showed low molecule overlap. In addition to benzene and acyclic compounds, flavones, coumarins, and flavanones were identified as the most frequent molecular scaffolds across the different natural products collections. The results of this work have direct implications in the computational and experimental screening of natural product databases for drug discovery. © 2012 John Wiley & Sons A/S.

Measuring Quality Gaps in TB Screening in South Africa Using Standardised Patient Analysis

PubMed Central

Christian, Carmen S.; Gerdtham, Ulf-G.; Hompashe, Dumisani; Smith, Anja; Burger, Ronelle

2018-01-01

This is the first multi-district Standardised Patient (SP) study in South Africa. It measures the quality of TB screening at primary healthcare (PHC) facilities. We hypothesise that TB screening protocols and best practices are poorly adhered to at the PHC level. The SP method allows researchers to observe how healthcare providers identify, test and advise presumptive TB patients, and whether this aligns with clinical protocols and best practice. The study was conducted at PHC facilities in two provinces and 143 interactions at 39 facilities were analysed. Only 43% of interactions resulted in SPs receiving a TB sputum test and being offered an HIV test. TB sputum tests were conducted routinely (84%) while HIV tests were offered less frequently (47%). Nurses frequently neglected to ask SPs whether their household contacts had confirmed TB (54%). Antibiotics were prescribed without taking temperatures in 8% of cases. The importance of returning to the facility to receive TB test results was only explained in 28%. The SP method has highlighted gaps in clinical practice, signalling missed opportunities. Early detection of sub-optimal TB care is instrumental in decreasing TB-related morbidity and mortality. The findings provide the rationale for further quality improvement work in TB management. PMID:29649095

Use of a screening tool and primary health care gerontology nurse specialist for high-needs older people.

PubMed

King, Anna; Boyd, Michal; Dagley, Lynelle

2017-02-01

To describe implementation of an innovative gerontology nurse specialist role within one primary health organisation in Auckland, New Zealand. Quantitative outcomes of the screening tool as well as the nurse specialist assessment will be presented. The intervention involved use of the Brief Risk Identification for Geriatric Health Tool (BRIGHT) to identify high-needs older people with subsequent comprehensive geriatric assessment (CGA) performed by the gerontology nurse specialist. A total 384 of the 416 BRIGHTs were completed (92% response rate) and 15% of these were identified as high risk (n = 57). The BRIGHTs for high-risk older people revealed the highest scoring question was 'needing help with housework' (26%). The most frequent intervention by the gerontology nurse specialist was education (30%). The primary health care gerontology nurse specialist model delivers a proactive case finding and specialist gerontology intervention for older people at high risk of functional or health decline.

Detection of large scale 3′ deletions in the PMS2 gene amongst Colon-CFR participants – have we been missing anything?

PubMed Central

Clendenning, Mark; Walsh, Michael D; Gelpi, Judith Balmana; Thibodeau, Stephen N.; Lindor, Noralane; Potter, John D.; Newcomb, Polly; LeMarchand, Loic; Haile, Robert; Gallinger, Steve; Hopper, John L.; Jenkins, Mark A.; Rosty, Christophe; Young, Joanne P.; Buchanan, Daniel D.

2013-01-01

Current screening practices have been able to identify PMS2 mutations in 78% of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3′ end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22% (n = 16) of CRC-affected probands for mutations in the 3′ end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3′ deletions in PMS2 are not a frequent occurrence in such families. PMID:23288611

Risk factors for sensorineural hearing loss in children.

PubMed

Núñez-Batalla, Faustino; Trinidad-Ramos, Germán; Sequí-Canet, José Miguel; Alzina De Aguilar, Valentín; Jáudenes-Casaubón, Carmen

2012-01-01

In the last decade, tremendous progress has been made very rapidly in the development of Early Hearing Detection and Intervention (EHDI) systems as a major public health initiative. The percentage of infants screened annually in Spain has increased significantly since the EHDI systems have expanded to all autonomic regions. Historically, high risk indicators have been used for the identification of infants who should receive audiological evaluation but who live in geographic locations where universal hearing screening is not yet available, to help identify infants who pass neonatal screening but are at risk of developing delayed-onset hearing loss and to identify infants who may have passed neonatal screening but have mild forms of permanent hearing loss. In this review, the standard risk factors for hearing loss are analysed and the risk factors known to be associated with late onset or progressive hearing loss are identified. The recommendation for infants with a risk factor that may be considered as low risk is to perform at least one audiology assessment by 24-30 months. In contrast, for an infant with risk factors known to be associated with late onset or progressive hearing loss (such as cytomegalovirus infection or family history), early and more frequent assessment is appropriate. All infants should have an objective standardised screening of global development with a validated assessment tool at 9, 18 and 24-30 months of age or at any time if the health care professional or the family is concerned. Copyright © 2011 Elsevier España, S.L. All rights reserved.

web cellHTS2: a web-application for the analysis of high-throughput screening data.

PubMed

Pelz, Oliver; Gilsdorf, Moritz; Boutros, Michael

2010-04-12

The analysis of high-throughput screening data sets is an expanding field in bioinformatics. High-throughput screens by RNAi generate large primary data sets which need to be analyzed and annotated to identify relevant phenotypic hits. Large-scale RNAi screens are frequently used to identify novel factors that influence a broad range of cellular processes, including signaling pathway activity, cell proliferation, and host cell infection. Here, we present a web-based application utility for the end-to-end analysis of large cell-based screening experiments by cellHTS2. The software guides the user through the configuration steps that are required for the analysis of single or multi-channel experiments. The web-application provides options for various standardization and normalization methods, annotation of data sets and a comprehensive HTML report of the screening data analysis, including a ranked hit list. Sessions can be saved and restored for later re-analysis. The web frontend for the cellHTS2 R/Bioconductor package interacts with it through an R-server implementation that enables highly parallel analysis of screening data sets. web cellHTS2 further provides a file import and configuration module for common file formats. The implemented web-application facilitates the analysis of high-throughput data sets and provides a user-friendly interface. web cellHTS2 is accessible online at http://web-cellHTS2.dkfz.de. A standalone version as a virtual appliance and source code for platforms supporting Java 1.5.0 can be downloaded from the web cellHTS2 page. web cellHTS2 is freely distributed under GPL.

Occupational therapy needs of patients with thoracic cancer at the time of diagnosis: findings of a dedicated rehabilitation service.

PubMed

Bentley, Rachel; Hussain, Asmah; Maddocks, Matthew; Wilcock, Andrew

2013-06-01

Guidelines recommend screening patients with cancer to identify their rehabilitation needs. To help quantify this area of need and associated workload from an occupational therapy perspective in patients with thoracic cancer, we report the experiences of a dedicated rehabilitation service. Consecutive patients were screened soon after diagnosis using items associated with occupational performance in the Sheffield Profile for Assessment and Referral for Care questionnaire. Those reporting predetermined levels of distress underwent a full occupational therapy evaluation; this generated a problem list from which individualised goals and interventions were instigated. Of 540 patients screened, 273 (51 %) reported levels of distress which warranted a full occupational therapy assessment. Of these, 260 (95%) reported a total of 681 problems (median of 4 [2-5] per patient). Mostly these lay within the domain of self care (553, 78%) in the categories of transfers, functional mobility and bathing/showering. A total of 646 goals (median of 2 [1-3] per patient) were formulated, resulting in 652 individual interventions, most frequently the provision of equipment (79%) or advice (32%) and referral to another professional/agency (23%). Patients considered that most goals were achieved (98%) and that the provision of equipment was useful (97%). About half of patients with thoracic cancer screened have occupational therapy needs around the time of diagnosis. Problems are mostly in the area of self-care, with equipment provision the most frequent intervention provided. Future work should examine the efficacy of occupational therapy interventions further.

Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study.

PubMed

Jennings, Lance C; Priest, Patricia C; Psutka, Rebecca A; Duncan, Alasdair R; Anderson, Trevor; Mahagamasekera, Patalee; Strathdee, Andrew; Baker, Michael G

2015-06-01

There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers. Copyright © 2015 Elsevier B.V. All rights reserved.

Expanded Newborn Screening Program in Saudi Arabia: Incidence of screened disorders.

PubMed

Alfadhel, Majid; Al Othaim, Ali; Al Saif, Saif; Al Mutairi, Fuad; Alsayed, Moeenaldeen; Rahbeeni, Zuhair; Alzaidan, Hamad; Alowain, Mohammed; Al-Hassnan, Zuhair; Saeedi, Mohamad; Aljohery, Saeed; Alasmari, Ali; Faqeih, Eissa; Alwakeel, Mansour; AlMashary, Maher; Almohameed, Sulaiman; Alzahrani, Mohammed; Migdad, Abeer; Al-Dirbashi, Osama Y; Rashed, Mohamed; Alamoudi, Mohamed; Jacob, Minnie; Alahaidib, Lujane; El-Badaoui, Fahd; Saadallah, Amal; Alsulaiman, Ayman; Eyaid, Wafaa; Al-Odaib, Ali

2017-06-01

To address the implementation of the National Newborn Screening Program (NBS) in Saudi Arabia and stratify the incidence of the screened disorders. A retrospective study conducted between 1 August 2005 and 31 December 2012, total of 775 000 newborns were screened from 139 hospitals distributed among all regions of Saudi Arabia. The NBS Program screens for 16 disorders from a selective list of inborn errors of metabolism (IEM) and endocrine disorders. Heel prick dry blood spot samples were obtained from all newborns for biochemical and immunoassay testing. Recall screening testing was performed for Initial positive results and confirmed by specific biochemical assays. A total of 743 cases were identified giving an overall incidence of 1:1043. Frequently detected disorders nationwide were congenital hypothyroidism and congenital adrenal hyperplasia with an incidence of 1:7175 and 1:7908 correspondingly. The highest incidence among the IEM was propionic acidaemia with an incidence rate of 1:14 000. The article highlights the experience of the NBS Program in Saudi Arabia and providing data on specific regional incidences of all the screened disorders included in the programme; and showed that the incidence of these disorders is one of the highest reported so far world-wide. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

What Do Patients Want to Know? Questions and Concerns Regarding Mammography Expressed Through Social Media.

PubMed

Charlie, Abbas M; Gao, Yiming; Heller, Samantha L

2017-12-05

The purpose of this project is to identify questions and concerns patients have regarding breast cancer screening mammography to establish priorities in patient education and health care communication. A content analysis of posted questions (June 2010 to February 2017) containing the keywords mammogram and mammography was conducted on the social media question and answer website Quora (Quora Inc, Mountainview, California). Question topic, responses, and number of views were recorded. Comparisons were made by respondent type (medical professional or nonmedical professional) for screening recommendations and accompanying evidence. Descriptive statistics were employed to summarize the results. Overall, 197,620 views of mammography-related questions were identified, focused on 51 questions and 172 responses (51 of 172 [29.7%] by medical professionals [n = 25]; 121 of 172 [70.3%] by nonmedical professionals [n = 121]). Mammographic efficacy (16 of 51 [31.4%]) and screening guidelines (10 of 51 [19.6%]) were the most frequently queried topics. Overall, the majority of respondents were supportive of screening mammography. Most medical professionals recommended screening mammography starting at age 40, even after revisions in guidelines. Among nonmedical professionals, 4 of 22 (18.2%) were against screening mammography with less consensus regarding appropriate age of initial screen. Health society websites and journal articles were the most commonly referenced sources among medical and nonmedical professionals, respectively. A considerable interest in screening mammography guidelines and mammographic efficacy exists among users who seek health information on a social media question and answer website. Awareness of such platforms allows a unique opportunity for targeted health education and dissemination of accurate information, which may be able to reach a potentially untapped or hard-to-reach patient population. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Frequency and Determinants of a Short-Interval Follow-up Recommendation After an Abnormal Screening Mammogram.

PubMed

Pelletier, Eric; Daigle, Jean-Marc; Defay, Fannie; Major, Diane; Guertin, Marie-Hélène; Brisson, Jacques

2016-11-01

After imaging assessment of an abnormal screening mammogram, a follow-up examination 6 months later is recommended to some women. Our aim was to identify which characteristics of lesions, women, and physicians are associated to such short-interval follow-up recommendation in the Quebec Breast Cancer Screening Program. Between 1998 and 2008, 1,839,396 screening mammograms were performed and a total of 114,781 abnormal screens were assessed by imaging only. Multivariate analysis was done with multilevel Poisson regression models with robust variance and generalized linear mixed models. A short-interval follow-up was recommended in 26.7% of assessments with imaging only, representing 2.3% of all screens. Case-mix adjusted proportion of short-interval follow-up recommendations varied substantially across physicians (range: 4%-64%). Radiologists with high recall rates (≥15%) had a high proportion of short-interval follow-up recommendation (risk ratio: 1.82; 95% confidence interval: 1.35-2.45) compared to radiologists with low recall rates (<5%). The adjusted proportion of short-interval follow-up was high (22.8%) even when a previous mammogram was usually available. Short-interval follow-up recommendation at assessment is frequent in this Canadian screening program, even when a previous mammogram is available. Characteristics related to radiologists appear to be key determinants of short-interval follow-up recommendation, rather than characteristics of lesions or patient mix. Given that it can cause anxiety to women and adds pressure on the health system, it appears important to record and report short-interval follow-up and to identify ways to reduce its frequency. Short-interval follow-up recommendations should be considered when assessing the burden of mammography screening. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Impact of Neonatal Screening and Surveillance for the TP53 R337H Mutation on Early Detection of Childhood Adrenocortical Tumors

PubMed Central

Custódio, Gislaine; Parise, Guilherme A.; Kiesel Filho, Nilton; Komechen, Heloisa; Sabbaga, Cesar C.; Rosati, Roberto; Grisa, Leila; Parise, Ivy Z.S.; Pianovski, Mara A.D.; Fiori, Carmem M.C.M.; Ledesma, Jorge A.; Barbosa, José Renato S.; Figueiredo, Francisco R.O.; Sade, Elis R.; Ibañez, Humberto; Arram, Sohaila B.I.; Stinghen, Sérvio T.; Mengarelli, Luciano R.; Figueiredo, Mirna M.O.; Carvalho, Danilo C.; Avilla, Sylvio G.A.; Woiski, Thiago D.; Poncio, Lisiane C.; Lima, Geneci F.R.; Pontarolo, Roberto; Lalli, Enzo; Zhou, Yinmei; Zambetti, Gerard P.; Ribeiro, Raul C.; Figueiredo, Bonald C.

2013-01-01

Purpose The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. Patients and Methods Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. Results Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). Conclusion These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable. PMID:23733769

Efficacy and Cost-effectiveness of the Children’s Oncology Group Long-Term Follow-Up Screening Guidelines for Childhood Cancer Survivors at Risk of Treatment-related Heart Failure

PubMed Central

Wong, F. Lennie; Bhatia, Smita; Landier, Wendy; Francisco, Liton; Leisenring, Wendy; Hudson, Melissa M.; Armstrong, Gregory T.; Mertens, Ann; Stovall, Marilyn; Robison, Leslie L.; Lyman, Gary H.; Lipshultz, Steven E.; Armenian, Saro H.

2014-01-01

Background Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure (HF), and death. The consensus-based Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines recommend lifetime echocardiographic screening for ALVD. Objective To evaluate the efficacy and cost-effectiveness of the COG Guidelines and to identify more cost-effective screening strategies. Design Simulation of life-histories using Markov health states. Data Sources Childhood Cancer Survivor Study; published literature. Target Population Childhood cancer survivors. Time Horizon Lifetime. Perspective Societal. Intervention Echocardiographic screening, followed by angiotensin-converting enzyme (ACE) inhibitor and beta-blocker therapies after ALVD diagnosis. Measurements Quality-adjusted life years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and the cumulative incidence of HF. Results of Base-Case Analysis The COG Guidelines versus no screening have an ICER of $61,500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of HF by 18% at 30 years after cancer diagnosis. However, less-frequent screenings are more cost-effective than the Guidelines, and maintain 80% of the health benefits. Results of Sensitivity Analysis The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. Limitation Lifetime non-HF mortality and the cumulative incidence of HF more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and beta-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). Conclusion The COG Guidelines could reduce the risk of HF in survivors at less than $100,000/QALY. Less-frequent screening achieves most of the benefits and would be more cost-effective than the COG Guidelines. Primary Funding Source Lance Armstrong Foundation, National Cancer Institute. PMID:24842414

Correlates of mobile screen media use among children aged 0–8: a systematic review

PubMed Central

Jancey, Jonine; Subedi, Narayan; Leavy, Justine

2017-01-01

Objective This study is a systematic review of the peer-reviewed literature to identify the correlates of mobile screen media use among children aged 8 years and less. Setting Home or community-based studies were included in this review while child care or school-based studies were excluded. Participants Children aged 8 years or less were the study population. Studies that included larger age groups without subgroup analysis specific to the 0–8 years category were excluded. Eight electronic databases were searched for peer-reviewed English language primary research articles published or in press between January 2009 and March 2017 that have studied correlates of mobile screen media use in this age group. Outcome measure Mobile screen media use was the primary outcome measure. Mobile screen media use refers to children’s use of mobile screens, such as mobile phones, electronic tablets, handheld computers or personal digital assistants. Results Thirteen studies meeting the inclusion criteria were identified of which a total of 36 correlates were examined. Older children, children better skilled in using mobile screen media devices, those having greater access to such devices at home and whose parents had high mobile screen media use were more likely to have higher use of mobile screen media devices. No association existed with parent’s age, sex and education. Conclusion Limited research has been undertaken into young children’s mobile screen media use and most of the variables have been studied too infrequently for robust conclusions to be reached. Future studies with objective assessment of mobile screen media use and frequent examination of the potential correlates across multiple studies and settings are recommended. Trial registration number This review is registered with PROSPERO International Prospective Register of Ongoing Systematic Reviews (registration number: CRD42015028028). PMID:29070636

Correlates of mobile screen media use among children aged 0-8: a systematic review.

PubMed

Paudel, Susan; Jancey, Jonine; Subedi, Narayan; Leavy, Justine

2017-10-24

This study is a systematic review of the peer-reviewed literature to identify the correlates of mobile screen media use among children aged 8 years and less. Home or community-based studies were included in this review while child care or school-based studies were excluded. Children aged 8 years or less were the study population. Studies that included larger age groups without subgroup analysis specific to the 0-8 years category were excluded. Eight electronic databases were searched for peer-reviewed English language primary research articles published or in press between January 2009 and March 2017 that have studied correlates of mobile screen media use in this age group. Mobile screen media use was the primary outcome measure. Mobile screen media use refers to children's use of mobile screens, such as mobile phones, electronic tablets, handheld computers or personal digital assistants. Thirteen studies meeting the inclusion criteria were identified of which a total of 36 correlates were examined. Older children, children better skilled in using mobile screen media devices, those having greater access to such devices at home and whose parents had high mobile screen media use were more likely to have higher use of mobile screen media devices. No association existed with parent's age, sex and education. Limited research has been undertaken into young children's mobile screen media use and most of the variables have been studied too infrequently for robust conclusions to be reached. Future studies with objective assessment of mobile screen media use and frequent examination of the potential correlates across multiple studies and settings are recommended. This review is registered with PROSPERO International Prospective Register of Ongoing Systematic Reviews (registration number: CRD42015028028). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States

PubMed Central

Miller, Marcus J.; Burrage, Lindsay C.; Gibson, James B.; Strenk, Meghan E.; Lose, Edward J.; Bick, David P.; Elsea, Sarah H.; Sutton, V. Reid; Sun, Qin; Graham, Brett H.; Craigen, William J.; Zhang, Victor Wei; Wong, Lee-Jun C.

2016-01-01

Very long chain acyl-coA dehydrogenase deficiency (VLCADD) is an autosomal recessive inborn error of fatty acid oxidation detected by newborn screening (NBS). Follow-up molecular analyses are often required to clarify VLCADD-suggestive NBS results, but to date the outcome of these studies are not well described for the general screen-positive population. In the following study, we report the molecular findings for 693 unrelated patients that sequentially received Sanger sequence analysis of ACADVL as a result of a positive NBS for VLCADD. Highlighting the variable molecular underpinnings of this disorder, we identified 94 different pathogenic ACADVL variants (40 novel), as well as 134 variants of unknown clinical significance (VUSs). Evidence for the pathogenicity of a subset of recurrent VUSs was provided using multiple in silico analyses. Surprisingly, the most frequent finding in our cohort was carrier status, 57% all individuals had a single pathogenic variant or VUS. This result was further supported by follow-up array and/or acylcarnitine analysis that failed to provide evidence of a second pathogenic allele. Notably, exon-targeted array analysis of 131 individuals screen positive for VLCADD failed to identify copy number changes in ACADVL thus suggesting this test has a low yield in the setting of NBS follow-up. While no genotype was common, the c.848T>C (p.V283A) pathogenic variant was clearly the most frequent; at least one copy was found in ∼10% of all individuals with a positive NBS. Clinical and biochemical data for seven unrelated patients homozygous for the p.V283A allele suggests that it results in a mild phenotype that responds well to standard treatment, but hypoglycemia can occur. Collectively, our data illustrate the molecular heterogeneity of VLCADD and provide novel insight into the outcomes of NBS for this disorder. PMID:26385305

Otologic blast injuries due to the Kenya embassy bombing.

PubMed

Helling, Eric Robert

2004-11-01

Otologic injuries are frequently associated with large blasts. On August 7, 1998, a large truck bomb exploded next to the U.S. Embassy in Nairobi, Kenya. Initial patient findings and care are reviewed. Five months later, an otologic screening and care mission was then sent to comprehensively screen all remaining blast victims on site in Nairobi and to determine degree of persistent injury. Surgical care appropriate for an outpatient environment was provided. Five of 14 tympanic membranes without intervention failed to heal, while 3 of 3 with previous intervention had. Blast injury severity did not correlate to distance from blast epicenter. This may be due to channeling of the blast through the embassy building and an unpredictable pattern of blast overpressure within the building. It is recommended that comprehensive otologic screening be performed after blast events to identify occult injuries and improve outcomes. Early intervention for tympanic membrane perforation (suctioning, eversion of perforations, and paper patch) is recommended.

Asymptomatic bacteriuria: review and discussion of the IDSA guidelines.

PubMed

Nicolle, Lindsay E

2006-08-01

Asymptomatic bacteriuria is a common finding, but is usually benign. Screening and treatment of asymptomatic bacteriuria is only recommended for pregnant women, or for patients prior to selected invasive genitourinary procedures. Healthy women identified with asymptomatic bacteriuria on population screening subsequently experience more frequent episodes of symptomatic infection, but antimicrobial treatment of asymptomatic bacteriuria does not decrease the occurrence of these episodes. Clinical trials in spinal-cord injury patients, diabetic women, patients with indwelling urethral catheters, and elderly nursing home residents have consistently found no benefits with treatment of asymptomatic bacteriuria. Negative outcomes with antimicrobial treatment do occur, including adverse drug effects and re-infection with organisms of increasing resistance. Optimal management of asymptomatic bacteriuria requires appropriate implementation of screening strategies to promote timely identification of the selected patients for whom treatment is beneficial, and avoidance of antimicrobial therapy where no benefit has been shown.

Koilocytosis and squamous (pre)neoplasia as detected in population-based cervical screening: practice and theory.

PubMed

Boon, M E; Boon, L M; de Bosschere, M J A; Verbruggen, B S M; Kok, L P

2005-01-01

Koilocytosis (cavitation of the cytoplasm due to active HPV infection) can be detected in the screening process for cervical carcinoma. To report the practice of detection of koilocytosis and (pre)neoplasia in population screening and to exploit the collected data to propose an explanation for the relationship between HPV infection and nuclear precancerous changes. Centrally collected and stored (SBBW, Leiden, the Netherlands) data from all smears of six regional pathology laboratories (1995-2002), coded according to KOPAC (the national cervical smear coding system; S1: normal thru S9: invasive carcinoma) were accessed. Prevalences per 100,000 smears were calculated for koilocytosis and for squamous abnormalities after stratification for country of origin of screenees. The relative risk (RR) for the ethnic (age) groups was computed by dividing the prevalence of the relevant ethnic (age) group by the prevalence of all women. Surinamese women featured the highest prevalence of koilocytosis and of all squamous abnormalities. Moroccan women the lowest. The RR for koilocytosis was highest at 30 years (1.84) and lowest at 60 (0.26). RR dependence on age of S5-S9 lesions was similar. Compared to nonkoilocytotic smears, koilocytosis was 104 times more frequent in the 1,500 S4 smears, 36x more frequent in the 6,700 S2-S3 smears, and 24x more frequent in the 1,740 S5-S9 smears. In all three categories this difference is statistically significant. High prevalences for both koilocytosis and for preneoplasia were detected in Surinamese immigrants, however, it still does not exclude HPV infection as a confounder linked to sexual lifestyle. The presence of koilocytosis in cervical smears may serve to identify patients with an increased risk for cervical cancer and perhaps warrant more intensive surveillance than what is provided through five-yearly screening.

Bacterial interactomes: Interacting protein partners share similar function and are validated in independent assays more frequently than previously reported.

DOE PAGES

Shatsky, Maxim; Allen, Simon; Gold, Barbara; ...

2016-05-01

Numerous affinity purification – mass-spectrometry (AP-MS) and yeast two hybrid (Y2H) screens have each defined thousands of pairwise protein-protein interactions (PPIs), most between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial Y2H and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared to the nine published interactomes, our two networks are smaller; are much less highly connected; have significantly lower false discovery rates; and are much moremore » enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays. Lastly, our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested.« less

Influences of Radiology Trainees on Screening Mammography Interpretation.

PubMed

Hawley, Jeffrey R; Taylor, Clayton R; Cubbison, Alyssa M; Erdal, B Selnur; Yildiz, Vedat O; Carkaci, Selin

2016-05-01

Participation of radiology trainees in screening mammographic interpretation is a critical component of radiology residency and fellowship training. The aim of this study was to investigate and quantify the effects of trainee involvement on screening mammographic interpretation and diagnostic outcomes. Screening mammograms interpreted at an academic medical center by six dedicated breast imagers over a three-year period were identified, with cases interpreted by an attending radiologist alone or in conjunction with a trainee. Trainees included radiology residents, breast imaging fellows, and fellows from other radiology subspecialties during breast imaging rotations. Trainee participation, patient variables, results of diagnostic evaluations, and pathology were recorded. A total of 47,914 mammograms from 34,867 patients were included, with an overall recall rate for attending radiologists reading alone of 14.7% compared with 18.0% when involving a trainee (P < .0001). Overall cancer detection rate for attending radiologists reading alone was 5.7 per 1,000 compared with 5.2 per 1,000 when reading with a trainee (P = .517). When reading with a trainee, dense breasts represented a greater portion of recalls (P = .0001), and more frequently, greater than one abnormality was described in the breast (P = .013). Detection of ductal carcinoma in situ versus invasive carcinoma or invasive cancer type was not significantly different. The mean size of cancers in patients recalled by attending radiologists alone was smaller, and nodal involvement was less frequent, though not statistically significantly. These results demonstrate a significant overall increase in recall rate when interpreting screening mammograms with radiology trainees, with no change in cancer detection rate. Radiology faculty members should be aware of this potentiality and mitigate tendencies toward greater false positives. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia

PubMed Central

Desmaison, Annaïck; Vigouroux, Adeline; Rieubland, Claudine; Peres, Christine; Calvas, Patrick

2010-01-01

Purpose Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia. Methods Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries. Results Two heterozygous variants of unknown significance (c.128C>G [p.Pro43Arg]; c.776C>A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C>A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C>G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father. Conclusions Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia. PMID:21203406

Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia.

PubMed

Desmaison, Annaïck; Vigouroux, Adeline; Rieubland, Claudine; Peres, Christine; Calvas, Patrick; Chassaing, Nicolas

2010-12-18

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia. Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries. Two heterozygous variants of unknown significance (c.128C>G [p.Pro43Arg]; c.776C>A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C>A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C>G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father. Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia.

The Association Between Primary Source of Healthcare Coverage and Colorectal Cancer Screening Among US Veterans.

PubMed

May, Folasade P; Yano, Elizabeth M; Provenzale, Dawn; Neil Steers, W; Washington, Donna L

2017-08-01

Colorectal cancer (CRC) is a deadly but largely preventable disease. Screening improves outcomes, but screening rates vary across healthcare coverage models. In the Veterans Health Administration (VA), screening rates are high; however, it is unknown how CRC screening rates compare for Veterans with other types of healthcare coverage. To determine whether Veterans with Veteran-status-related coverage (VA, military, TRICARE) have higher rates of CRC screening than Veterans with alternate sources of healthcare coverage. We conducted a cross-sectional analysis of Veterans 50-75 years from the 2014 Behavioral Risk Factor Surveillance System survey. We examined CRC screening rates and screening modalities. We performed multivariable logistic regression to identify the role of coverage type, demographics, and clinical factors on screening status. The cohort included 22,138 Veterans. Of these, 76.7% reported up-to-date screening. Colonoscopy was the most common screening modality (83.7%). Screening rates were highest among Veterans with Veteran-status-related coverage (82.3%), as was stool-based screening (10.8%). The adjusted odds of up-to-date screening among Veterans with Veteran-status-related coverage were 83% higher than among Veterans with private coverage (adjusted OR = 1.83, 95% CI = 1.52-2.22). Additional predictors of screening included older age, black race, high income, access to medical care, frequent medical visits, and employed or married status. CRC screening rates were highest among Veterans with Veteran-status-related coverage. High CRC screening rates among US Veterans may be related to system-level characteristics of VA and military care. Insight to these system-level characteristics may inform mechanisms to improve CRC screening in non-VA settings.

[Analysis of tools, methods and results of toxicological screening for detection of drug abuse in Italian professional drivers].

PubMed

Rosso, G L

2013-01-01

Three years after a protocol agreement between the State and the Regions came into force in 2008 (drug testing at the workplace Law) a large number of studies have been conducted to analyse and test the efficacy of on-site screening tests for detection of drug consumption (opiates, cocaine, cannabinoids, amphetamine and methamphetamine, MDMA and methadone), which are frequently used by the occupational health physician, and also to present data resulting from workplace drug testing obtained during health surveillance programmes. The aim of the present study was to verify whether the features of sensitivity and specificity of the most common on-site testing ensure correct application of the provisions of current Italian legislation and also to analyse published studies showing the frequency of positive drug testing. A review of Italian and international literature was carried out aimed at identifying studies relating to: (1) performance of on-site screening tests frequently used by the occupational health physician, (2) prevalence of drug use/abuse among Italian public and commercial transport drivers. A comparison between the studies was then carried out. Several rapid on-site screening tests are commercially available (Italian law does not provide standards for the technical specifications of the tests), the sensitivity and specificity of which varies depending on the model and the substance tested. The sensitivity of these tools is poor when used for the detection of low concentrations of drugs and/or their metabolites in urine (close to the cut-off). Studies are lacking that compare on-site tests performed by the occupational health physician and confirmative tests in specialized laboratories (with particular regard to false positives found by the occupational health physician). The major studies in terms of methods and/or size reported a positive rate (confirmed at the first level) between 1.6% and 1.9%. The drugs most frequently used/abused were cannabis and cocaine. The performance of on-site screening tests (to detect psychotropic substances on urine matrix) and the methodology required by Italian law show that the aims of Italian workplace drug testing legislation have not been achieved The low positive rate observed in Italian studies could be due to an error in the first phase of screening performed by the occupational health physician.

Human papillomavirus infection in women attended at a cervical cancer screening service in Natal, Brazil

PubMed Central

de Medeiros Fernandes, Thales Allyrio Araújo; de Vasconcellos Meissner, Rosely; Bezerra, Laelson Freire; de Azevedo, Paulo Roberto Medeiros; Fernandes, José Veríssimo

2008-01-01

We analyzed cervical specimens of 202 women, aged 15 to 64 years, attended at Luis Antonio Hospital, Natal, Brazil, to determine the prevalence of HPV and identify the more frequent genotypes and risk factors for HPV infection in women attended at a cervical cancer screening service. Two specimens were collected from each patient: one for cytological examination and the other to detect HPV DNA by PCR, and typing by dot blot hybridization. A total of 54.5% of the sample had normal cytology and 45.5% had cytological alterations. HPV was detected in 24.5% of the cytologically normal women and in 59.8% of those with altered cytology. Both single and double HPV infection increased the likelihood of cytological alterations. Thirteen types of HPV were identified, most of which were high risk. HPV 16 was the most prevalent single-type infection, followed by HPV 58. The most frequent double infection was the association between HPV 56 and 57. The prevalence of HPV in cytologically normal women was greater than that reported for countries on all the continents except Africa. The inverse was observed in women with cytological alterations. The distribution of HPV types was similar to that described for the Americas, with some differences. Multiple sexual partners was the only risk factor showing an association with the presence of HPV infection. PMID:24031268

Frequent emergency department presentations among people who inject drugs: A record linkage study.

PubMed

Nambiar, Dhanya; Stoové, Mark; Dietze, Paul

2017-06-01

People who inject drugs (PWID) have been described as frequent users of health services such as emergency departments (EDs), however few studies have described demographic factors, patterns of substance use and previous health service use associated with frequent use of EDs in this population. Using a combination of self-reported data from a cohort of PWID and administrative ED data obtained through record linkage, we identified longitudinal factors associated with the use of ED services. Bivariate and multivariate analyses were conducted using negative binomial regression to identify exposures associated with both cumulative ED presentations, and logistic regression to identify exposures of frequent ED presentations (defined as three or more annual presentations). Among 612 PWID, over half (58%) presented to EDs at least once and over a third (36%) presented frequently between January 2008 and June 2013. Frequent and cumulative ED presentations were associated with reporting the main drug of choice as cannabis (AOR:1.42, 95%CI:1.07-1.89 and AIRR:2.96, 95%CI:1.44-6.07 respectively) or methamphetamine (AOR:1.62, 95%CI:1.17-2.2 and AIRR:2.42, 95%CI:1.08-5.46 respectively) compared to heroin, and past month use of mental health (AOR:1.42, 95%CI:1.08-1.85 and AIRR:3.32, 95%CI:1.69-6.53 respectively) and outpatient services (AOR:1.47, 95%CI: 1.00-2.16 and AIRR:0.95, 95%CI 1.52-10.28 respectively). PWID who are frequent users of EDs are likely to have complex health and substance use-related needs. EDs should actively refer people who present with cannabis and methamphetamine dependence to harm reduction services. Harm reduction services should ensure people referred from EDs are screened for co-occurring mental health conditions and receive adequate support. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydroxychloroquine screening practice patterns within a large multispecialty ophthalmic practice.

PubMed

Au, Adrian; Parikh, Vishal; Modi, Yasha S; Ehlers, Justis P; Schachat, Andrew P; Singh, Rishi P

2015-09-01

To determine provider compliance with hydroxychloroquine screening following the revised recommendations published in 2011 by the American Academy of Ophthalmology. Evaluation of adherence to a screening protocol. Subjects were identified with hydroxychloroquine as a medication by electronic query at a large multispecialty ophthalmic practice. Patients were excluded if patients: (1) were screened by an outside physician; (2) lacked recorded height, weight, start date, or dosing; or (3) took hydroxychloroquine for malaria prophylaxis. Screening tests were stratified by ophthalmic subspecialty. Guidelines define proper screening as 1 subjective test-Humphrey visual field (HVF), and 1 objective test-spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), or multifocal electroretinography (mfERG). Adherence to guidelines was determined by categorizing practices as: (1) "appropriate"-consistent with guidelines; (2) "underscreened"-insufficient testing; or (3) "inappropriate"-no testing. The study comprised 756 patients with a mean age of 56 years undergoing 1294 screening visits. Twenty-one patients received initial screenings outside the institution. Most common screening tests employed included SD OCT (56.6%), 10-2 HVF (55.0%), and Amsler grid (40.0%). Of the 735 initial screenings, 341 (46.4%) were appropriately screened, 204 (27.8%) underscreened, and 190 (25.9%) inappropriately screened. Of those who presented solely for screening (560), 307 (54.8%) were appropriately screened, 144 (25.7%) underscreened, and 109 (19.5%) inappropriately screened. Of patients presenting for hydroxychloroquine screening, 54.8% of patients received appropriate evaluation, indicating lack of adherence to guidelines. Overall, SD OCT and 10-2 HVF were the preferred screening modalities, with FAF and mfERG less frequently ordered. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of the Sydney Falls Risk Screening Tool in brain injury rehabilitation: A multisite prospective cohort study.

PubMed

McKechnie, Duncan; Fisher, Murray J; Pryor, Julie; Bonser, Melissa; Jesus, Jhoven De

2018-03-01

To develop a falls risk screening tool (FRST) sensitive to the traumatic brain injury rehabilitation population. Falls are the most frequently recorded patient safety incident within the hospital context. The inpatient traumatic brain injury rehabilitation population is one particular population that has been identified as at high risk of falls. However, no FRST has been developed for this patient population. Consequently in the traumatic brain injury rehabilitation population, there is the real possibility that nurses are using falls risk screening tools that have a poor clinical utility. Multisite prospective cohort study. Univariate and multiple logistic regression modelling techniques (backward elimination, elastic net and hierarchical) were used to examine each variable's association with patients who fell. The resulting FRST's clinical validity was examined. Of the 140 patients in the study, 41 (29%) fell. Through multiple logistic regression modelling, 11 variables were identified as predictors for falls. Using hierarchical logistic regression, five of these were identified for inclusion in the resulting falls risk screening tool: prescribed mobility aid (such as, wheelchair or frame), a fall since admission to hospital, impulsive behaviour, impaired orientation and bladder and/or bowel incontinence. The resulting FRST has good clinical validity (sensitivity = 0.9; specificity = 0.62; area under the curve = 0.87; Youden index = 0.54). The tool was significantly more accurate (p = .037 on DeLong test) in discriminating fallers from nonfallers than the Ontario Modified STRATIFY FRST. A FRST has been developed using a comprehensive statistical framework, and evidence has been provided of this tool's clinical validity. The developed tool, the Sydney Falls Risk Screening Tool, should be considered for use in brain injury rehabilitation populations. © 2017 John Wiley & Sons Ltd.

Lung cancers diagnosed at annual CT screening: volume doubling times.

PubMed

Henschke, Claudia I; Yankelevitz, David F; Yip, Rowena; Reeves, Anthony P; Farooqi, Ali; Xu, Dongming; Smith, James P; Libby, Daniel M; Pasmantier, Mark W; Miettinen, Olli S

2012-05-01

To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

Motivators and barriers to mammography screening uptake by female health-care workers in primary health-care centres: a cross-sectional study.

PubMed

Nazzal, Zaher; Sholi, Hisham; Sholi, Suha B; Sholi, Mohammad B; Lahaseh, Rawya

2018-02-21

Mammography screening is an effective tool for early detection and management of breast cancer. Female health-care workers' awareness of breast cancer screening is important because their beliefs and behaviours could influence other women. The aim of this study was to assess mammography screening uptake by female health-care workers at primary health-care centres and to identify the primary motivators and barriers that affect uptake. This cross-sectional study included all governmental primary health-care centres in the West Bank. Governorates were grouped into three regions as follows: north West Bank (Nablus, Jenin, Tulkarm, Tubas, Qalqiliya, and Salfit), middle West Bank (Jerusalem, Jericho, and Ramallah), and south West Bank (Hebron, and Bethlehem). The study population included all female health-care workers older than 40 years. Those who performed mammography for a suspected mass or other breast abnormalities were excluded. A self-administered questionnaire was used to collect data on demographic characteristics, knowledge about mammography screening, the extent and regularity of mammography screening, and motivators and barriers influencing their mammography screening uptake. The rate of mammography screening uptake was calculated. χ 2 test and t tests were used to assess screening motivators and barriers. The study was approved by the Institutional Review Board of the An-Najah National University. Participation was voluntary, and written consent was obtained from each participant. 299 female health-care workers completed a self-administered questionnaire. The mean age of the participants was 46 years (SD 4·7). 284 (95%) women had adequate knowledge about breast cancer and mammography screening, and 149 (50%) women reported having had at least one mammogram. 62 (21%) women had had regular scheduled mammograms. The most frequent reported motivators were the perceived benefit that early detection of breast cancer is important for its management (269 [90%] women) and the belief that mammography can detect breast cancer before its symptoms appear (251 [84%] women). The most frequent barrier to mammography screening was being busy (140 [47%] women) and the lack of perceived susceptibility (125 [42%] women). Mammography screening was suboptimal in a population of female health-care workers. Educational interventions are needed to remove barriers that limit compliance to recommendations and to emphasise the importance of early detection in breast cancer management. Ensuring the availability and accessibility of screening services, particularly for health-care workers within their work settings, would improve the acceptance and compliance for mammography screening programmes. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhanced HTS hit selection via a local hit rate analysis.

PubMed

Posner, Bruce A; Xi, Hualin; Mills, James E J

2009-10-01

The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

The effect of major depression on participation in preventive health care activities

PubMed Central

Patten, Scott B; Williams, Jeanne VA; Lavorato, Dina H; Eliasziw, Michael

2009-01-01

Background The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests. Methods The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening. Results No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result. Conclusion Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening. PMID:19320983

A high frequency of distinct ATM gene mutations in ataxia-telangiectasia.

PubMed Central

Wright, J.; Teraoka, S.; Onengut, S.; Tolun, A.; Gatti, R. A.; Ochs, H. D.; Concannon, P.

1996-01-01

The clinical features of the autosomal recessive disorder ataxia-telangiectasia (AT) include a progressive cerebellar ataxia, hypersensitivity to ionizing radiation, and an increased susceptibility to malignancies. Epidemiological studies have suggested that AT heterozygotes may also be at increased risk for malignancy, possibly as a consequence of radiation exposure. A gene mutated in AT patients (ATM) has recently been isolated, making mutation screening in both patients and the general population possible. Because of the relatively large size of the ATM gene, the design of screening programs will depend on the types and distribution of mutations in the general population. In this report, we describe 30 mutations identified in a panel of unrelated AT patients and controls. Twenty-five of the 30 were distinct, and most patients were compound heterozygotes. The most frequently detected mutation was found in three different families and had previously been reported in five others. This corresponds to a frequency of 8% of all reported ATM mutations. Twenty-two of the alterations observed would be predicted to lead to protein truncation at sites scattered throughout the molecule. Two fibroblast cell lines, which displayed normal responses to ionizing radiation, also proved to be heterozygous for truncation mutations of ATM. These observations suggest that the carrier frequency of ATM mutations may be sufficiently high to make population screening practical. However, such screening may need to be done prospectively, that is, by searching for new mutations rather than by screening for just those already identified in AT families. PMID:8808599

Identifiability in N-mixture models: a large-scale screening test with bird data.

PubMed

Kéry, Marc

2018-02-01

Binomial N-mixture models have proven very useful in ecology, conservation, and monitoring: they allow estimation and modeling of abundance separately from detection probability using simple counts. Recently, doubts about parameter identifiability have been voiced. I conducted a large-scale screening test with 137 bird data sets from 2,037 sites. I found virtually no identifiability problems for Poisson and zero-inflated Poisson (ZIP) binomial N-mixture models, but negative-binomial (NB) models had problems in 25% of all data sets. The corresponding multinomial N-mixture models had no problems. Parameter estimates under Poisson and ZIP binomial and multinomial N-mixture models were extremely similar. Identifiability problems became a little more frequent with smaller sample sizes (267 and 50 sites), but were unaffected by whether the models did or did not include covariates. Hence, binomial N-mixture model parameters with Poisson and ZIP mixtures typically appeared identifiable. In contrast, NB mixtures were often unidentifiable, which is worrying since these were often selected by Akaike's information criterion. Identifiability of binomial N-mixture models should always be checked. If problems are found, simpler models, integrated models that combine different observation models or the use of external information via informative priors or penalized likelihoods, may help. © 2017 by the Ecological Society of America.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parthasarathy, Srinandini; McKone, Thomas E.; Apte, Michael G.

This report summarizes the screening procedure and its results for selecting contaminants of concern (COC), whose concentrations are affected by ventilation in commercial buildings. Many pollutants comprising criteria pollutants, volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs) and biological contaminants are found in commercial buildings. In this report, we focus primarily on identifying potential volatile organic COC, which are impacted by ventilation. In the future we plan to extend this effort to inorganic gases and particles. Our screening considers compounds detected frequently in indoor air and compares the concentrations to health-guidelines and thresholds. However, given the range of buildings undermore » consideration, the contaminant sources and their concentrations will vary depending on the activity and use of the buildings. We used a literature review to identify a large list of chemicals found in commercial-building indoor air. The VOCs selected were subject to a two stage screening process, and the compounds of greater interest are included in priority List A. Other VOCs that have been detected in commercial buildings are included in priority List B. The compounds in List B, were further classified into groups B1, B2, B3, B4 in order of decreasing interest.« less

Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours.

PubMed

Kajiura, Koichiro; Takizawa, Hiromitsu; Morimoto, Yuki; Masuda, Kiyoshi; Tsuboi, Mitsuhiro; Kishibuchi, Reina; Wusiman, Nuliamina; Sawada, Toru; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Kawakami, Yukikiyo; Naruto, Takuya; Imoto, Issei; Tangoku, Akira; Kondo, Kazuya

2017-09-01

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET. Copyright © 2017 Elsevier B.V. All rights reserved.

A survey of attitudes, behaviors, and needs of team dentists.

PubMed

McGovern, Lesley A; Spolarich, Ann Eshenaur; Keim, Robert

2015-01-01

Elite athletes strive to attain superior levels of health and fitness; however, many have high levels of oral disease. Oral screenings detect disease and need for treatment and identify opportunities for preventive interventions. Many dentists volunteer their time with sports organizations, but their scope of practice and needs are unknown. The purposes of this study were to gather baseline data about attitudes, practice behaviors, and needs of team dentists and to assess dental services provided, including the type and frequency of oral screenings conducted on athletes and any associated barriers to those screenings. This descriptive study utilized an original online survey, comprising 37 supplied-response questions, that was pilot tested for face and content validity. All dentist members of the Academy for Sports Dentistry were invited to participate (n = 491), and 150 responded, yielding a 31% response rate. The survey format allowed respondents to skip questions, and some respondents chose not to answer some questions. Quantitative data collected included level of athletes, league affiliation, scope of services provided, and types of oral screening performed. Dentists' attitudes regarding athletes' treatment and preventive needs, practice behaviors, and self-identified needs were assessed. Descriptive statistics were used to analyze the data. Results revealed that 116 of 146 respondents (80%) had a league affiliation. Among 112 dentists who reported providing services to athletes, the most frequently provided services were emergency treatment (96%), mouthguards (96%), restorative treatment (79%), oral hygiene instruction (63%), prophylaxis (61%), periodontal charting (61%), and dental charting (60%). Most team dentists (80%; n = 90/112) performed oral screenings for the athletes. Among 87 respondents who performed screenings and reported the type of screening they provided, 36 (41%) screened all athletes prior to the season and then provided individualized follow-up examinations as needed. The most commonly cited barrier to screenings was lack of awareness of the importance of oral health. Additional education for athletes, coaches, owners, schools, and leagues is needed to increase the value placed on oral health.

Screening in Primary Care: What Is the Best Way to Identify At-Risk Youth for Substance Use?

PubMed

D'Amico, Elizabeth J; Parast, Layla; Meredith, Lisa S; Ewing, Brett A; Shadel, William G; Stein, Bradley D

2016-12-01

It is important to improve primary care providers' capability to identify youth at risk for alcohol and other drug use. To our knowledge, this is the first study to use Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria to compare screeners for youth for both alcohol and marijuana, given that these are the most frequently used substances by this age group. We compared the psychometric performance of 4 screeners: the National Institute on Alcohol Abuse and Alcoholism Screening Guide (NIAAA SG), the Alcohol Use Disorders Identification Test, the Car-Relax-Alone-Forget-Family and Friends-Trouble (CRAFFT) screener, and the Personal Experience Screening Questionnaire Problem Severity Scale (PESQ-PS) in identifying alcohol and marijuana use outcomes. Youth age 12 through 18 (N = 1573; 27% black, 51% Hispanic) were screened with the NIAAA SG, followed by a Web survey that included the other screeners and outcomes. Sensitivity for alcohol outcomes indicated that the NIAAA SG (0.87) did not perform as well as the CRAFFT (0.97) or PESQ-PS (0.97) screeners but performed better than the Alcohol Use Disorders Identification Test (0.70). The pattern for sensitivity across screeners for marijuana outcomes was similar. An important tradeoff in primary care settings is precision versus practicality. Because of brevity and focus on frequency of drinking, the NIAAA SG offers ease of administration and is good at identifying youth with probably problematic drinking levels. The PESQ-PS and the CRAFFT correctly identify more at-risk youth for alcohol and marijuana than the NIAAA SG. Future work is needed to elucidate how to efficiently and accurately identify at-risk youth in the primary care setting, including determining the best cutoff points to use to increase sensitivity. Copyright © 2016 by the American Academy of Pediatrics.

Rapidly progressive heart failure requiring transplantation in muscular dystrophy: a need for frequent screening.

PubMed

Pick, Justin M; Ellis, Zachary D; Alejos, Juan C; Chang, Anthony C

2017-11-01

Fukuyama congenital muscular dystrophy weakens both skeletal and cardiac muscles, but the rate of cardiomyopathic progression can accelerate faster than that of skeletal muscles. A 14-year-old boy with Fukuyama congenital muscular dystrophy presented with mild skeletal myopathy but severe cardiomyopathy requiring heart transplantation within 1 year of declining heart function. These patients need frequent screening regardless of musculoskeletal symptoms.

Evaluation of rapid SYS system as screen for Yersinia enterocolitica in the United States.

PubMed Central

Mele, L; Nadler, H; Gomez, S

1987-01-01

Clinical isolates (n = 150) from stool specimens were selected for evaluation of the Rapid SYS system (Analytab Products, Plainview, N.Y.) as a screening test for Shigella spp., Yersinia enterocolitica, and Salmonella spp. The Gram-Negative Identification Card (Vitek Systems, Inc., Hazelwood, Mo.) was used for identification. Although acceptable performance of the Rapid SYS system was described, the interpretative criteria provided by the vendor for previous studies led to inappropriate screening for Y. enterocolitica, particularly biotype 1. When corrected screening criteria were used for the present study, the sensitivity for the detection of 76 enteric pathogens was 98.7%. Of the 76 pathogens, 1 of 21 Shigella spp. was not detected. However, specificity was only 16.6% when 72 selected nonpathogens frequently encountered in stools were eliminated. Although the Rapid SYS system can identify Shigella spp., Y. enterocolitica, and Salmonella spp., only phenylalanine deaminase-producing and cytochrome oxidase-producing organisms can be eliminated from additional testing. Therefore, the Rapid SYS system cannot be used as a three-pathogen screen in the United States or in other geographic locales where Y. enterocolitica biotype 1 may be encountered. PMID:3323232

Perceived barriers to implementing screening and brief intervention for alcohol consumption by adolescents in hospital emergency department in Spain.

PubMed

Falcón, María; Navarro-Zaragoza, Javier; García-Rodríguez, Rosa María; Nova-López, Daniel; González-Navarro, María Dulce; Mercadal, María; García-Algar, Oscar; Luna Ruiz-Cabello, Aurelio

2017-07-14

Screening for alcohol consumption in adolescents is widely justified in the health care field because of the particular vulnerability of this population, which starts drinking alcohol at a very early age and frequently consumes high levels of the same. Hospital emergency departments (ED) could be a good venue to manage early detection and carry out brief intervention (BI) programmes. The aim of this study was to identify perceived barriers for medical staff of three hospitals in Spain to successfully implement a protocol for alcohol detection and BI for minors in the ED. Exploratory qualitative analysis using focus groups with semi-structured, flexible and open-ended questions to explore beliefs, attitudes, and barriers perceived by professionals to screening alcohol consumption and implementing BI in adolescents attended at the ED. The main perceived barriers by health professionals were lack of time, work overload, mistrust, lack of validated and simple screening tools, lack of training/awareness and legal concerns about informed consent and confidentiality. Barriers to screening and intervention in ED are similar to those described previously. It is necessary to improve organization of time allocated for medical consultations, avoid limiting ED resources, motivate staff and provide appropriate training.

Factors facilitating acceptable mammography services for women with disabilities

PubMed Central

Jarman, Molly P.; Bowling, J. Michael; Dickens, Pamela; Luken, Karen; Yankaskas, Bonnie C.

2012-01-01

Introduction and Background Prior research has described general barriers to breast cancer screening for women with disabilities (WWD). We explored specific accommodations described as necessary by WWD who have accessed screening services, and the presence of such accommodations in community based screening programs. Methods We surveyed WWD in the Carolina Mammography Registry to determine what accommodations were needed when accessing breast screening services, and whether or not these needs were met. The sample of 1,348 WWD was identified through a survey of limitations, with a response rate of 45.5% (4,498/9,885). Of the 1,348 WWD eligible for the second survey, 739 responded for a response rate of 54.8%. Results The most frequently needed accommodations were an accessible changing area with a bench (60.0%), oral description of the procedure by the technologist (60.5%), and handicapped/accessible parking (27.6%). Handicapped parking was the need most likely to go unmet (3.1%). Conclusions Most needs are being met by radiology facilities and staff, and the few needs going unmet are related to the physical/built environment. Overall, for WWD who are in screening, the mammography system appears to be more accessible than generally perceived. PMID:22818248

Photoaffinity labeling in target- and binding-site identification

PubMed Central

Smith, Ewan; Collins, Ian

2015-01-01

Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas. PMID:25686004

Establishing an Australian nurse practitioner-led colorectal cancer screening clinic.

PubMed

Morcom, Joylene; Dunn, Sandra V; Luxford, Yoni

2005-01-01

In Australia, colorectal cancer is the most commonly occurring internal cancer affecting both men and women, and the second most common cause of cancer-related death. Flexible sigmoidoscopy has not been commonly used as a screening tool in Australia due primarily to lack of resources. Until now, people at average risk of developing bowel cancer frequently undergo colonoscopy after referral to a specialist. To fill an identified need, a nurse practitioner-led colorectal screening service providing fecal occult blood testing and flexible sigmoidoscopy, health education and promotion, patient counseling, information and a referral point for general practitioners, and a referral service for above average-risk patients was established in a South Australian metropolitan teaching hospital. Establishment of this clinic required advanced and extended theoretical and clinical preparation for the nurse practitioner, as well as development of interdisciplinary relationships, referral processes, clinical infrastructure, and a marketing strategy. An audit of the first 100 flexible sigmoidoscopy patients revealed service and procedural outcomes that compared favorably with other colorectal screening services as well as a high level of patient satisfaction.

Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library

PubMed Central

Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

2016-01-01

With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim–sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim–sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim–sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

Cost-Effectiveness of Osteoporosis Screening Strategies for Men

PubMed Central

Nayak, Smita; Greenspan, Susan L.

2016-01-01

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for U.S. men involving various screening tests (dual-energy x-ray absorptiometry (DXA); the Osteoporosis Self-Assessment Tool (OST); or a fracture risk assessment strategy using age, femoral neck bone mineral density (BMD), and Vertebral Fracture Assessment (VFA)); screening initiation ages (50, 60, 70, or 80); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was “dominated” by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analysis and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/QALY or $100,000/QALY included screening initiation at age 50 with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for U.S. men to initiate routine screening at age 50 or 60 would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. PMID:26751984

A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene.

PubMed

Gobeil, Stephane; Zhu, Xiaochun; Doillon, Charles J; Green, Michael R

2008-11-01

Metastasis suppressor genes inhibit one or more steps required for metastasis without affecting primary tumor formation. Due to the complexity of the metastatic process, the development of experimental approaches for identifying genes involved in metastasis prevention has been challenging. Here we describe a genome-wide RNAi screening strategy to identify candidate metastasis suppressor genes. Following expression in weakly metastatic B16-F0 mouse melanoma cells, shRNAs were selected based upon enhanced satellite colony formation in a three-dimensional cell culture system and confirmed in a mouse experimental metastasis assay. Using this approach we discovered 22 genes whose knockdown increased metastasis without affecting primary tumor growth. We focused on one of these genes, Gas1 (Growth arrest-specific 1), because we found that it was substantially down-regulated in highly metastatic B16-F10 melanoma cells, which contributed to the high metastatic potential of this mouse cell line. We further demonstrated that Gas1 has all the expected properties of a melanoma tumor suppressor including: suppression of metastasis in a spontaneous metastasis assay, promotion of apoptosis following dissemination of cells to secondary sites, and frequent down-regulation in human melanoma metastasis-derived cell lines and metastatic tumor samples. Thus, we developed a genome-wide shRNA screening strategy that enables the discovery of new metastasis suppressor genes.

Racial and gender variation in use of diagnostic colonic procedures in the Michigan Medicare population.

PubMed

McMahon, L F; Wolfe, R A; Huang, S; Tedeschi, P; Manning, W; Edlund, M J

1999-07-01

There is accumulating evidence that screening programs can alter the natural history of colorectal cancer, a significant cause of mortality and morbidity in the US. Understanding how the technology to diagnose colonic diseases is utilized in the population provides insight into both the access and processes of care. Using Medicare Part B billing files from the state of Michigan from 1986 to 1989 we identified all procedures used to diagnose colorectal disease. We utilized the Medicare Beneficiary File and the Area Resource File to identify beneficiary-specific and community-sociodemographic characteristics. The beneficiary and sociodemographic characteristics were, then, used in multiple regression analyses to identify their association with procedure utilization. Sigmoidoscopic use declined dramatically with the increasing age cohorts of Medicare beneficiaries. Urban areas and communities with higher education levels had more sigmoidoscopic use. Among procedures used to examine the entire colon, isolated barium enema was used more frequently in African Americans, the elderly, and females. The combination of barium enema and sigmoidoscopy was used more frequently among females and the newest technology, colonoscopy, was used most frequently among White males. The existence of race, gender, and socioeconomic disparities in the use of colorectal technologies in a group of patients with near-universal insurance coverage demonstrates the necessity of understanding the reason(s) for these observed differences to improve access to appropriate technologies to all segments in our society.

Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

PubMed

Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

2009-07-01

The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

Cancer screening in a middle-aged general population: factors associated with practices and attitudes

PubMed Central

Cullati, Stéphane; Charvet-Bérard, Agathe I; Perneger, Thomas V

2009-01-01

Background The aim of this study was to identify factors associated with cancer screening practices and with general attitudes toward cancer screening in a general population. Methods Mailed survey of 30–60 year old residents of Geneva, Switzerland, that included questions about screening for five cancers (breast, cervix uteri, prostate, colon, skin) in the past 3 years, attitudes toward screening, health care use, preventive behaviours and socio-demographic characteristics. Cancer screening practice was dichotomised as having done at least one screening test in the past 3 years versus none. Results The survey response rate was 49.3% (2301/4670). More women than men had had at least one cancer screening test in the past 3 years (83.2% vs 34.5%, p < 0.001). A majority of women had had a cervical smear (76.6%) and a mammography (age 30–49: 35.0%; age 50 and older: 90.3%); and 55.1% of men 50–60 years old had been screened for prostate cancer. Other factors associated with screening included older age, higher income, a doctor visit in the past 6 months, reporting a greater number of preventive behaviours and a positive attitude toward screening. Factors linked with positive attitudes included female gender, higher level of education, gainful employment, higher income, a doctor visit in the past 6 months and a personal history of cancer. Conclusion Attitudes play an important role in cancer screening practices among middle-aged adults in the general population, independent of demographic variables (age and sex) that determine in part screening recommendations. Negative attitudes were the most frequent among men and the most socio-economically disadvantaged. The moderate participation rate raises the possibility of selection bias. PMID:19402895

Bacterial Interactomes: Interacting Protein Partners Share Similar Function and Are Validated in Independent Assays More Frequently Than Previously Reported*

PubMed Central

Shatsky, Maxim; Allen, Simon; Gold, Barbara L.; Liu, Nancy L.; Juba, Thomas R.; Reveco, Sonia A.; Elias, Dwayne A.; Prathapam, Ramadevi; He, Jennifer; Yang, Wenhong; Szakal, Evelin D.; Liu, Haichuan; Singer, Mary E.; Geller, Jil T.; Lam, Bonita R.; Saini, Avneesh; Trotter, Valentine V.; Hall, Steven C.; Fisher, Susan J.; Brenner, Steven E.; Chhabra, Swapnil R.; Hazen, Terry C.; Wall, Judy D.; Witkowska, H. Ewa; Biggin, Mark D.; Chandonia, John-Marc; Butland, Gareth

2016-01-01

Numerous affinity purification-mass spectrometry (AP-MS) and yeast two-hybrid screens have each defined thousands of pairwise protein-protein interactions (PPIs), most of which are between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here, we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial yeast two-hybrid and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared with the nine published interactomes, our two networks are smaller, are much less highly connected, and have significantly lower false discovery rates. In addition, our interactomes are much more enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays than the pairs reported in prior studies. Our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested. PMID:26873250

Suicidal adolescents' experiences with bullying perpetration and victimization during high school as risk factors for later depression and suicidality.

PubMed

Klomek, Anat Brunstein; Kleinman, Marjorie; Altschuler, Elizabeth; Marrocco, Frank; Amakawa, Lia; Gould, Madelyn S

2013-07-01

This is the first study to examine the extent to which frequent involvement in high-school bullying (as a bullying perpetrator, victim of bullying, or bully-victim) increases the risk for later depression and suicidality beyond other well-established risk factors of suicide. The study included 96 students who reported being a bully, a victim, or a bully-victim, and also reported depression, suicidality, or substance problems during an initial suicide screen. These students were interviewed 2 years later and were compared with 142 youth identified during the initial screen as "suicide-at-risk" by virtue of their depression, suicidal ideation, attempts, and substance problems, but who did not report any involvement in bullying behavior. Students who reported both bullying others and other suicide-related behaviors at baseline had higher suicide ideation and were more functionally impaired at follow-up than students who reported suicide-related behaviors but were not involved in bullying. Preventive efforts in high school should target those children who are characterized by both psychological disturbance and bullying, especially the frequent bullies. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

A false positive newborn screening result due to a complex allele carrying two frequent CF-causing variants.

PubMed

Bergougnoux, Anne; Boureau-Wirth, Amandine; Rouzier, Cécile; Altieri, Jean-Pierre; Verneau, Fanny; Larrieu, Lise; Koenig, Michel; Claustres, Mireille; Raynal, Caroline

2016-05-01

The detection of two frequent CFTR disease-causing variations in the context of a newborn screening program (NBS) usually leads to the diagnosis of cystic fibrosis (CF) and a relevant genetic counseling in the family. In the present study, CF-causing variants p.Phe508del (F508del) and c.3140-26A>G (3272-26A>G) were identified on a neonate with positive ImmunoReactive Trypsinogen test by the Elucigene™ CF30 kit. The CF diagnosis initially suggested, despite three inconclusive Sweat Chloride Tests (SCT), was finally ruled out after the familial segregation study combined with a negative SCT. Haplotype studies, based on the comparison of 80 p.Phe508del haplotypes, suggested a probable de novo occurrence of c.3140-26A>G on the p.Phe508del ancestral allele in this family. This false positive case emphasizes the importance of SCT in the NBS strategy. Moreover, it raises the need for familial segregation studies in CF and in overall molecular diagnosis strategy of autosomal recessive diseases. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Meta-analysis: the association of oesophageal adenocarcinoma with symptoms of gastro-oesophageal reflux

PubMed Central

Rubenstein, J. H.; Taylor, J. B.

2012-01-01

Background Endoscopic screening has been proposed for patients with symptoms of gastro-oesophageal reflux disease (GERD) in the hope of reducing mortality from oesophageal adenocarcinoma. Assessing the net benefits of such a strategy requires a precise understanding of the cancer risk in the screened population. Aim To estimate precisely the association between symptoms of GERD and oesophageal adenocarcinoma. Methods Systematic review and meta-analysis of population-based studies with strict ascertainment of exposure and outcomes. Results Five eligible studies were identified. At least weekly symptoms of GERD increased the odds of oesophageal adenocarcinoma fivefold (odds ratio = 4.92; 95% confidence interval = 3.90, 6.22), and daily symptoms increased the odds sevenfold (random effects summary odds ratio = 7.40, 95% confidence interval = 4.94, 11.1), each compared with individuals without symptoms or less frequent symptoms. Duration of symptoms was also associated with oesophageal adenocarcinoma, but with very heterogeneous results, and unclear thresholds. Conclusions Frequent GERD symptoms are strongly associated with oesophageal adenocarcinoma. These results should be useful in developing epidemiological models of the development of oesophageal adenocarcinoma, and in models of interventions aimed at reducing mortality from this cancer. PMID:20955441

Modeling the Impact of School-based Universal Depression Screening on Additional Service Capacity Needs: A System Dynamics Approach

PubMed Central

Lyon, Aaron R.; Maras, Melissa A.; Pate, Christina M.; Igusa, Takeru; Stoep, Ann Vander

2016-01-01

Although it is widely known that the occurrence of depression increases over the course of adolescence, symptoms of mood disorders frequently go undetected. While schools are viable settings for conducting universal screening to systematically identify students in need of services for common health conditions, particularly those that adversely affect school performance, few school districts routinely screen their students for depression. Among the most commonly referenced barriers are concerns that the number of students identified may exceed schools’ service delivery capacities, but few studies have evaluated this concern systematically. System dynamics (SD) modeling may prove a useful approach for answering questions of this sort. The goal of the current paper is therefore to demonstrate how SD modeling can be applied to inform implementation decisions in communities. In our demonstration, we used SD modeling to estimate the additional service demand generated by universal depression screening in a typical high school. We then simulated the effects of implementing “compensatory approaches” designed to address anticipated increases in service need through (1) the allocation of additional staff time and (2) improvements in the effectiveness of mental health interventions. Results support the ability of screening to facilitate more rapid entry into services and suggest that improving the effectiveness of mental health services for students with depression via the implementation of an evidence-based treatment protocol may have a limited impact on overall recovery rates and service availability. In our example, the SD approach proved useful in informing systems’ decision-making about the adoption of a new school mental health service. PMID:25601192

Is More Screening Better? The Relationship between Frequent Screening, Accurate Decisions, and Reading Proficiency

ERIC Educational Resources Information Center

VanDerHeyden, Amanda M.; Burns, Matthew K.; Bonifay, Wesley

2018-01-01

Screening is necessary to detect risk and prevent reading failure. Yet the amount of screening that commonly occurs in U.S. schools may undermine its value, creating more error in decision making and lost instructional opportunity. This 2-year longitudinal study examined the decision accuracy associated with collecting concurrent reading screening…

Screening Children for Family Violence: A Review of the Evidence for the US Preventive Services Task Force

PubMed Central

Nygren, Peggy; Nelson, Heidi D.; Klein, Jonathan

2004-01-01

BACKGROUND We wanted to evaluate the benefits and harms of screening children in primary health care settings for abuse and neglect resulting from family violence by examining the evidence on the performance of screening instruments and the effectiveness of interventions. METHODS We searched for relevant studies in MEDLINE, PsycINFO, CINAHL, ERIC, Cochrane Controlled Trials Register, and reference lists. English language abstracts with original data about family violence against children focusing on screening and interventions initiated or based in health care settings were included. We extracted selected information about study design, patient populations and settings, methods of assessment or intervention, and outcome measures, and applied a set of criteria to evaluate study quality. RESULTS All instruments designed to screen for child abuse and neglect were directed to parents, particularly pregnant women. These instruments had fairly high sensitivity but low specificity when administered in high-risk study populations and have not been widely tested in other populations. Randomized controlled trials of frequent nurse home visitation programs beginning during pregnancy that address behavioral and psychological factors indicated improved abuse measures and outcomes. No studies were identified about interventions in older children or harms associated with screening and intervention. CONCLUSIONS No trials of the effectiveness of screening in a health care setting have been published. Clinician referrals to nurse home visitation during pregnancy and in early childhood may reduce abuse in selected populations. There are no studies about harms of screening and interventions. PMID:15083858

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

PubMed Central

Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

2012-01-01

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

Screening of cardiovascular risk factors in patients with schizophrenia and patients treated with antipsychotic drugs: are we equally exhaustive as with the general population?

PubMed

Castillo-Sánchez, Miguel; Fàbregas-Escurriola, Mireia; Bergè-Baquero, Daniel; Fernández-SanMartín, MªIsabel; Goday-Arno, Albert

2017-01-01

Many studies have previously shown increased cardiovascular risk factors related to schizophrenia independently from the use of antipsychotic drugs. However, a poorer effort in clinical detection and management of cardiovascular risk in patients with severe mental illness could also explain these results. To test this hypothesis, we analyzed the differences in screening and incidence of cardiovascular risk factors between schizophrenia, non-schizophrenic patients on treatment with antipsychotic drugs (NS-TAD) and the general population. Data from adult subjects assessed by high-quality register general practitioners from 2006 to 2011 were extracted from the Catalonian SIDIAP database. The schizophrenia, NS-TAD, and control groups were compared in terms of measurements and incidence of diabetes, dyslipidemia, obesity, hypertension, and smoking. A total of 4911 patients in the schizophrenia group, 4157 in NS-TAD group, and 98644 in the control group were included. Schizophrenia patients were screened for dyslipidemia and diabetes more frequently than the control group, while for obesity or hypertension, they were screened equal to controls. Also, as compared to the control group, the NS-TAD group was more frequently screened for obesity with no differences in dyslipidemia and diabetes and less frequently for hypertension. Smoking was less frequently screened in both study groups. The incidence of all risk factors studied in both study groups was higher than or equal to the control group, except for hypertension, which had lower incidence. The lack of screening of risk factors does not appear decisive in the increased cardiovascular risk of patients diagnosed with schizophrenia seen in primary care. Studies evaluating the possible under diagnosis of the risk factors are required. Schizophrenia (SZ); Treatment with antipsychotic drugs (TAD); Cardiovascular risk factor/s (CVRF); Without schizophrenia but on therapy with antipsychotic drugs (NS-TAD); Defined Daily Dose (DDD).

Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6.

PubMed

Hill, Joshua A; Magaret, Amalia S; Hall-Sedlak, Ruth; Mikhaylova, Anna; Huang, Meei-Li; Sandmaier, Brenda M; Hansen, John A; Jerome, Keith R; Zerr, Danielle M; Boeckh, Michael

2017-08-24

Human herpesvirus 6 (HHV-6) species have a unique ability to integrate into chromosomal telomeres. Mendelian inheritance via gametocyte integration results in HHV-6 in every nucleated cell. The epidemiology and clinical effect of inherited chromosomally integrated HHV-6 (iciHHV-6) in hematopoietic cell transplant (HCT) recipients is unclear. We identified 4319 HCT donor-recipient pairs (8638 subjects) who received an allogeneic HCT and had archived pre-HCT peripheral blood mononuclear cell samples. We screened these samples for iciHHV-6 and compared characteristics of HCT recipients and donors with iciHHV-6 with those of recipients and donors without iciHHV-6, respectively. We calculated Kaplan-Meier probability estimates and Cox proportional hazards models for post-HCT outcomes based on recipient and donor iciHHV-6 status. We identified 60 HCT recipients (1.4%) and 40 donors (0.9%) with iciHHV-6; both recipient and donor harbored iciHHV-6 in 13 HCTs. Thus, there were 87 HCTs (2%) in which the recipient, donor, or both harbored iciHHV-6. Acute graft-versus-host disease (GVHD) grades 2-4 was more frequent when recipients or donors had iciHHV-6 (adjusted hazard ratios, 1.7-1.9; P = .004-.001). Cytomegalovirus viremia (any and high-level) was more frequent among recipients with iciHHV-6 (adjusted HRs, 1.7-3.1; P = .001-.040). Inherited ciHHV-6 status did not significantly affect risk for chronic GVHD, hematopoietic cell engraftment, overall mortality, or nonrelapse mortality. Screening for iciHHV-6 could guide donor selection and post-HCT risk stratification and treatment. Further study is needed to replicate these findings and identify potential mechanisms. © 2017 by The American Society of Hematology.

Predictors and dietary consequences of frequent intake of high-sugar, low-nutrient foods in 1-year-old children participating in the ABIS study.

PubMed

Brekke, Hilde K; van Odijk, Jenny; Ludvigsson, Johnny

2007-01-01

Foods rich in sugar have been suggested to contribute to the increasing prevalence of obesity in children. The aim of this report is to investigate the dietary pattern in 1-year-old children who frequently receive foods rich in sugar but low in nutrients and to study associated demographic and parental factors. During 1977-9, 21,700 infants were invited to participate in this prospective, population-based, longitudinal cohort study. Screening questionnaires were completed for 16,070 infants after delivery. Follow-up questionnaires from 10,762 children at 1 year of age are included in the analysis. It was found that 24% of the children received sweets/pastries more often than one or two times per week. They had a higher intake of French fries, potato crisps and cream as well as a lower intake of fruit and vegetables. A frequent intake of sugar-rich, low-nutrient foods was significantly associated with several maternal factors (high intake of sweets/pastries during pregnancy, young age, mother living alone) as well as presence of older siblings. Maternal smoking during pregnancy and maternal overweight were of borderline significance. Parental education level was inversely associated with the frequency of intake of sweets/pastries in the child. Children who frequently receive sweets/pastries also have an otherwise unfavourable dietary pattern. Several parental and demographic factors were associated with this feeding pattern, especially high intake of sweets/pastries during pregnancy. Screening of pregnant women for risk predictors like consumption of sweets/pastries, young age and smoking could be possible ways of identifying children at future risk for low dietary quality.

The James Supportive Care Screening: integrating science and practice to meet the NCCN guidelines for distress management at a Comprehensive Cancer Center.

PubMed

Wells-Di Gregorio, Sharla; Porensky, Emily K; Minotti, Matthew; Brown, Susan; Snapp, Janet; Taylor, Robert M; Adolph, Michael D; Everett, Sherman; Lowther, Kenneth; Callahan, Kelly; Streva, Devita; Heinke, Vicki; Leno, Debra; Flower, Courtney; McVey, Anne; Andersen, Barbara Lee

2013-09-01

Selecting a measure for oncology distress screening can be challenging. The measure must be brief, but comprehensive, capturing patients' most distressing concerns. The measure must provide meaningful coverage of multiple domains, assess symptom and problem-related distress, and ideally be suited for both clinical and research purposes. From March 2006 to August 2012, the James Supportive Care Screening (SCS) was developed and validated in three phases including content validation, factor analysis, and measure validation. Exploratory factor analyses were completed with 596 oncology patients followed by a confirmatory factor analysis with 477 patients. Six factors were identified and confirmed including (i) emotional concerns; (ii) physical symptoms; (iii) social/practical problems; (iv) spiritual problems; (v) cognitive concerns; and (vi) healthcare decision making/communication issues. Subscale evaluation reveals good to excellent internal consistency, test-retest reliability, and convergent, divergent, and predictive validity. Specificity of individual items was 0.90 and 0.87, respectively, for identifying patients with DSM-IV-TR diagnoses of major depression and generalized anxiety disorder. Results support use of the James SCS to quickly detect the most frequent and distressing symptoms and concerns of cancer patients. The James SCS is an efficient, reliable, and valid clinical and research outcomes measure. Copyright © 2013 John Wiley & Sons, Ltd.

Cervical cancer screening among women who attend sexually transmitted diseases (STD) clinics: background paper for 2010 STD Treatment Guidelines.

PubMed

Datta, S Deblina; Saraiya, Mona

2011-12-01

In April 2008, experts reviewed updates on sexually transmitted disease (STD) prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. This included a review of cervical cancer screening in the STD clinical setting. Key questions were identified with assistance from an expert panel. Reviews of the literature were conducted using the PubMed computerized database and shared with the panel. Updated information was incorporated in the 2010 CDC STD Treatment Guidelines. We recommend that STD clinics offering cervical screening services screen and treat women according to guidelines by the American College of Obstetrics and Gynecology, the American Cancer Society, the US Preventive Services Task Force, and the American Society for Colposcopists and Cervical Pathologists. New to the 2010 guidelines are higher age for initiating cervical screening (age ≥ 21 years) and less frequent intervals of screening (at least every 3 years). New recommendations include new technologies, such as liquid-based cytology and high-risk human papillomavirus (HPV) DNA tests. Liquid-based technologies are not recommended over conventional testing. HPV DNA tests are recommended as adjunct tests and with new indications for use in cervical screening and management. Stronger recommendations were issued for STD clinics offering cervical screening services to have protocols in place for follow-up of test results and referral (eg, colposcopy). Important additions to the 2010 STD Treatment Guidelines include information on updated algorithms for screening and management of women and recommendations for use of liquid-based cytology and high-risk HPV testing.

Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.

PubMed

Brito, Dulce; Miltenberger-Miltenyi, Gabriel; Vale Pereira, Sónia; Silva, Doroteia; Diogo, António Nunes; Madeira, Hugo

2012-09-01

Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown. Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients. Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease. Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss.

PubMed

Hildebrand, Michael S; Morín, Matías; Meyer, Nicole C; Mayo, Fernando; Modamio-Hoybjor, Silvia; Mencía, Angeles; Olavarrieta, Leticia; Morales-Angulo, Carmelo; Nishimura, Carla J; Workman, Heather; DeLuca, Adam P; del Castillo, Ignacio; Taylor, Kyle R; Tompkins, Bruce; Goodman, Corey W; Schrauwen, Isabelle; Wesemael, Maarten Van; Lachlan, K; Shearer, A Eliot; Braun, Terry A; Huygen, Patrick L M; Kremer, Hannie; Van Camp, Guy; Moreno, Felipe; Casavant, Thomas L; Smith, Richard J H; Moreno-Pelayo, Miguel A

2011-07-01

The prevalence of DFNA8/DFNA12 (DFNA8/12), a type of autosomal dominant nonsyndromic hearing loss (ADNSHL), is unknown as comprehensive population-based genetic screening has not been conducted. We therefore completed unbiased screening for TECTA mutations in a Spanish cohort of 372 probands from ADNSHL families. Three additional families (Spanish, Belgian, and English) known to be linked to DFNA8/12 were also included in the screening. In an additional cohort of 835 American ADNSHL families, we preselected 73 probands for TECTA screening based on audiometric data. In aggregate, we identified 23 TECTA mutations in this process. Remarkably, 20 of these mutations are novel, more than doubling the number of reported TECTA ADNSHL mutations from 13 to 33. Mutations lie in all domains of the α-tectorin protein, including those for the first time identified in the entactin domain, as well as the vWFD1, vWFD2, and vWFD3 repeats, and the D1-D2 and TIL2 connectors. Although the majority are private mutations, four of them-p.Cys1036Tyr, p.Cys1837Gly, p.Thr1866Met, and p.Arg1890Cys-were observed in more than one unrelated family. For two of these mutations founder effects were also confirmed. Our data validate previously observed genotype-phenotype correlations in DFNA8/12 and introduce new correlations. Specifically, mutations in the N-terminal region of α-tectorin (entactin domain, vWFD1, and vWFD2) lead to mid-frequency NSHL, a phenotype previously associated only with mutations in the ZP domain. Collectively, our results indicate that DFNA8/12 hearing loss is a frequent type of ADNSHL. © 2011 Wiley-Liss, Inc.

Molecular basis of cystic fibrosis in Lithuania: incomplete CFTR mutation detection by PCR-based screening protocols.

PubMed

Giannattasio, S; Bobba, A; Jurgelevicius, V; Vacca, R A; Lattanzio, P; Merafina, R S; Utkus, A; Kucinskas, V; Marra, E

2006-01-01

Mutational analysis of the cystic fibrosis transmembrane regulator (CFTR) gene was performed in 98 unrelated CF chromosomes from 49 Lithuanian CF patients through a combined approach in which the p.F508del mutation was first screened by allele-specific PCR while CFTR mutations in nonp.F508del chromosomes have been screened for by denaturing gradient gel electrophoresis analysis. A CFTR mutation was characterized in 62.2% of CF chromosomes, two of which (2.0%) have been previously shown to carry a large gene deletion CFTRdele2,3(21 kb). The most frequent Lithuanian CF mutation is p.F508del (52.0%). Seven CFTR mutations, p.N1303K (2.0%), p.R75Q (1.0%), p.G314R (1.0%), p.R553X (4.2%), p.W1282X (1.0%), and g.3944delGT (1.0%), accounted for 10.1% of Lithuanian CF chromosomes. It was not possible to characterize 35.8% of the CF Lithuanian chromosomes. Analysis of intron 8 (TG)mTn and M470V polymorphic loci did not permit the characterization of the CFTR dysfunction underlying the CF phenotype in the patients for which no CFTR mutation was identified. Thus, screening of the eight CFTR mutations identified in this study and of the large deletion CFTRdele2,3(21 kb) allows the implementation of an early molecular or confirmatory CF diagnosis for 65% of Lithuanian CF chromosomes.

Predictors of skin examination in California twins Prevalence and predictors of recent skin examination in a population-based twin cohort

PubMed Central

Miller, Kimberly A.; Langholz, Bryan M.; Zadnick, John; Hamilton, Ann S.; Cozen, Wendy; Mack, Thomas M.; Cockburn, Myles G.

2015-01-01

Background The incidence of melanoma is increasing worldwide. Guidelines for clinical skin exam for improving early diagnosis of melanoma remain inconsistent, and current data on factors associated with regular skin screening on a population basis are limited. Methods We used self-reported data from 50,044 members of the California Twin Program, a population-based cohort of twins born in California between 1908 and 1982, to identify prevalence and determinants of recent clinical screening for skin cancer. Results Prevalence of skin examination was higher than national estimates, with 32% of respondents of all ages reporting ever having skin examination. Socio-demographic and constitutional risk factors including white race, educational attainment, marital status, and number of large moles were strongly associated with recent screening, as were individual and family history of skin cancer. Lower socioeconomic status, racial/ethnic minority status, and paradoxically, frequent UV-related risk behaviors in adulthood were associated with a lower likelihood of recent screening. Conclusions As the evidence concerning the efficacy of skin examination continues to evolve, attention should be paid to motivators and barriers of screening, particularly in high-risk subgroups where lack of screening may contribute to disparate rates of thicker melanomas and lower survival. Impact Our results demonstrate the need for prevention strategies targeted to specific at-risk groups to increase earlier detection leading to improved outcomes. PMID:25994738

Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions

PubMed Central

Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander

2013-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409

C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population.

PubMed

Koutsis, Georgios; Karadima, Georgia; Kartanou, Chrisoula; Kladi, Athina; Panas, Marios

2015-01-01

An expanded hexanucleotide repeat in C9ORF72 has been identified as the most common genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia in many populations, including the Greek. Recently, C9ORF72 expansions were reported as the most common genetic cause of Huntington disease (HD) phenocopies in a UK population. In the present study, we screened a selected cohort of 40 Greek patients with HD phenocopies for C9ORF72 hexanucleotide repeat expansions using repeat-primed polymerase chain reaction. We identified 2 patients (5%) with pathologic expansions. The first patient had chorea, behavioral-psychiatric disturbance, cognitive impairment, and a positive family history, fulfilling the strictest criteria for HD phenocopy. The second patient was sporadic and had parkinsonism, behavioral-psychiatric disturbance, and cognitive impairment, corresponding to a broader definition of HD phenocopy. These findings identify C9ORF72 expansions as a frequent cause of HD phenocopies in the Greek population, confirming recent findings in other populations and supporting proposed diagnostic testing for C9ORF72 expansions in patients with HD-like syndromes. Copyright © 2015 Elsevier Inc. All rights reserved.

Isolation of Actinobacillus lignieresii and Actinobacillus equuli from laboratory rodents.

PubMed Central

Lentsch, R H; Wagner, J E

1980-01-01

Actinobacillus lignieresii and Actinobacillus equuli were cultured from a total of 36 guinea pigs, rats, and mice. The organisms were isolated from the oropharynx, the conjunctiva, and middle ear. Isolates were initially screened by eight biochemical tests to determine whether they were of the genus Actinobacillus. Actinobacillus spp. were then differentiated by fermentation reactions of nine carbohydrates. In the past, actinobacilli may have been mistakenly identified as Pasteurella spp., especially Pasteurella pneumotropica. The importance of realizing that Actinobacillus spp. are frequently isolated from laboratory rodents was stressed. PMID:7217333

Cystic fibrosis screening using the College panel: platform comparison and lessons learned from the first 20,000 samples.

PubMed

Strom, Charles M; Huang, Donghui; Buller, Arlene; Redman, Joy; Crossley, Beryl; Anderson, Ben; Entwistle, Tom; Sun, Weimin

2002-01-01

To determine the accuracy of two commercially available kits for cystic fibrosis (CF) genotyping and determine allele frequencies for the ACMG/ACOG recommended mutations. A total of 1,040 consecutive analyses using Roche CF Gold Strips and the ABI CF Genotyper were performed. Subsequently we performed analyses of 20,103 samples. Both kits accurately determined CF genotypes. The I148T mutation was found >100 times more frequently in carrier screening than in CF patients. Asymptomatic patients were identified who are compound heterozygotes for delta F508 and I148T. Four of 13 patients heterozygous for delta F508 and the IVS8-5T polymorphism had some symptoms of CF. Accurate and timely analysis can be performed for the ACMG CF panel. I148T is a low penetrance CF allele.

Cell-Free DNA-Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis.

PubMed

Nshimyumukiza, Léon; Beaumont, Jean-Alexandre; Duplantie, Julie; Langlois, Sylvie; Little, Julian; Audibert, François; McCabe, Christopher; Gekas, Jean; Giguère, Yves; Gagné, Christian; Reinharz, Daniel; Rousseau, François

2018-01-01

Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies. This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios. Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied. NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT. Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds.

PubMed

Yankelevitz, David F; Yip, Rowena; Smith, James P; Liang, Mingzhu; Liu, Ying; Xu, Dong Ming; Salvatore, Mary M; Wolf, Andrea S; Flores, Raja M; Henschke, Claudia I

2015-11-01

To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment. © RSNA, 2015

Are women positive for the One Step but negative for the Two Step screening tests for gestational diabetes at higher risk for adverse outcomes?

PubMed

Caissutti, Claudia; Khalifeh, Adeeb; Saccone, Gabriele; Berghella, Vincenzo

2018-02-01

The aim of this study was to evaluate if women meeting criteria for gestational diabetes mellitus (GDM) by the One Step test as per International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not by other less strict criteria have adverse pregnancy outcomes compared with GDM-negative controls. The primary outcome was the incidence of macrosomia, defined as birthweight > 4000 g. Electronic databases were searched from their inception until May 2017. All studies identifying pregnant women negative at the Two Step test, but positive at the One Step test for IADPSG criteria were included. We excluded studies that randomized women to the One Step vs. the Two Step tests; studies that compared different criteria within the same screening method; randomized studies comparing treatments for GDM; and studies comparing incidence of GDM in women doing the One Step test vs. the Two Step test. Eight retrospective cohort studies, including 29 983 women, were included. Five study groups and four control groups were identified. The heterogeneity between the studies was high. Gestational hypertension, preeclampsia and large for gestational age, as well as in some analyses cesarean delivery, macrosomia and preterm birth, were significantly more frequent, and small for gestational age in some analyses significantly less frequent, in women GDM-positive by the One Step, but not the Two Step. Women meeting criteria for GDM by IADPSG criteria but not by other less strict criteria have an increased risk of adverse pregnancy outcomes such as gestational hypertension, preeclampsia and large for gestational age, compared with GDM-negative controls. Based on these findings, and evidence from other studies that treatment decreases these adverse outcomes, we suggest screening for GDM using the One Step IADPSG criteria. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

MiraLAX-Gatorade Bowel Prep vs. GoLytely Prior to Screening Colonoscopy: An Endoscopic Database Study in a Community Hospital

PubMed Central

Shieh, Frederick K.; Gunaratnam, Naresh; Mohamud, Sagal O.; Schoenfeld, Philip

2012-01-01

Background Polyethylene Glycol-3350 without electrolytes (MiraLAX®; Schering-Plough Healthcare Products Inc.) + a carbohydrate-electrolyte solution (Gatorade; PepsiCo Inc.) + bisacodyl is frequently used for bowel cleansing, although limited data quantifies its efficacy and safety. No prior studies have assessed this in a community setting or with PM-only dosing, which is still used frequently. Aim To compare the frequency of excellent/good/fair/poor bowel cleansing with PM-only dosing of MiraLAX®-Gatorade-bisacodyl vs. 4L GoLytely®. Methods This is a retrospective endoscopic database analysis of ≥ 50 year old average-risk individuals with a normal screening colonoscopy at a community hospital and ambulatory endoscopy center. Data was extracted for the last four months when 4L GoLytely® was the preferred bowel purgative and the first 4 months when 238g MiraLAX® in 64 ounces Gatorade and four 5-mg bisacodyl tablets became the preferred purgative. All patients used PM-only dosing of bowel purgative. Results 778 subjects [GoLytely® (n=395) vs. MiraLAX® + Gatorade + bisacodyl (n=383)] were identified. Patients who took the MiraLAX® bowel preparation were more likely to achieve an excellent/good bowel cleansing compared to patients taking the GoLytely® preparation (93.3% vs. 89.3%, respectively; p = 0.048). However, when only ASA Class I patients are studied, there was no difference in frequency of excellent/good bowel cleansing (91.1% vs 93.6%, respectively; p = 0.498). No serious adverse events were identified. An excellent/good bowel cleansing was strongly associated with a recommendation for repeat colonoscopy in 10 years compared to patients with a fair cleansing [OR = 28.01; 95% CI: 13.96-56.19]. Conclusions The MiraLAX® + Gatorade + bisacodyl combination produces similar rates of excellent/good bowel cleansing as compared to GoLytely® in most average-risk individuals undergoing colonoscopy for CRC screening in a community setting. PMID:23060223

Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

PubMed Central

Butts, Arielle; DeJarnette, Christian; Peters, Tracy L.; Parker, Josie E.; Kerns, Morgan E.; Eberle, Karen E.; Kelly, Steve L.

2017-01-01

ABSTRACT Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. PMID:28989971

Use of a patient decision aid for prenatal screening for Down syndrome: what do pregnant women say?

PubMed

Portocarrero, Maria Esther Leiva; Giguère, Anik M C; Lépine, Johanie; Garvelink, Mirjam M; Robitaille, Hubert; Delanoë, Agathe; Lévesque, Isabelle; Wilson, Brenda J; Rousseau, François; Légaré, France

2017-03-20

Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors influencing pregnant women's use of a patient decision aid for deciding about prenatal screening for Down syndrome (DS). This qualitative study was embedded in a sequential mixed-methods research program whose main aim is to implement shared decision-making (SDM) in the context of prenatal screening for DS in the province of Quebec, Canada. We planned to recruit a purposive sample of 45 pregnant women with low-risk pregnancy consulting for prenatal care at three clinical sites. Participating women watched a video depicting a prenatal care follow-up during which a pregnant woman, her partner and a health professional used a PtDA to decide about prenatal screening for DS. The women were then interviewed about factors that would influence the use of this PtDA using questions based on the Theoretical Domains Framework (TDF). We performed content analysis of transcribed verbatim interviews. Out of 216 eligible women, 100 agreed to participate (46% response rate) and 46 were interviewed. Regarding the type of health professional responsible for their prenatal care, 19 participants (41%) reported having made a decision about prenatal screening for DS with an obstetrician-gynecologist, 13 (28%) with a midwife, 12 (26%) with a family physician, and two (4%) decided on their own. We identified 54 factors that were mapped onto nine of the 12 TDF domains. The three most frequently-mentioned were: opinion of the pregnant woman's partner (n = 33, 72%), presentation of the PtDA by health professional and a discussion (n = 27, 72%), and not having encountered a PtDA (n = 26, 57%). This study allowed us to identify factors influencing pregnant women's use of a PtDA for prenatal screening for DS. Use of a PtDA by health professionals and patients is one step in providing the needed decision support and our study results will allow us to design an effective implementation strategy for PtDAs for prenatal screening for DS.

Are cannabinoids an alternative for cachexia-anorexia syndrome in patients with advanced cancer?

PubMed

Cabeza, Claudia; Corsi, Oscar; Pérez-Cruz, Pedro

2017-12-29

Cachexia and anorexia are among the most frequent symptoms in patients with cancer. Cannabinoids have been used in patients with advanced cancer; however, their role is still controversial. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, and generated a summary of findings table using the GRADE approach. We identified ten systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have any positive effect on increasing weight because the certainty of the evidence is very low. They might not have any effect on appetite, and are probably associated to frequent adverse effects.

Large-scale screening and characterization of enteroviruses and kobuviruses infecting pigs in Vietnam

PubMed Central

Van Dung, Nguyen; Anh, Pham Hong; Van Cuong, Nguyen; Hoa, Ngo Thi; Carrique-Mas, Juan; Hien, Vo Be; Sharp, C.; Rabaa, M.; Berto, A.; Campbell, James; Baker, Stephen; Farrar, Jeremy; Woolhouse, Mark E.; Bryant, Juliet E.; Simmonds, Peter

2016-01-01

A recent survey of pigs in Dong Thap province, Vietnam identified a high frequency of enterovirus species G (EV-G) infection (144/198; 72.7 %). Amongst these was a plethora of EV-G types (EV-G1, EV-G6 and four new types EV-G8–EV-G11). To better characterize the genetic diversity of EV-G and investigate the possible existence of further circulating types, we performed a larger-scale study on 484 pig and 45 farm-bred boar faecal samples collected in 2012 and 2014, respectively. All samples from the previous and current studies were also screened for kobuviruses. The overall EV infection frequency remained extremely high (395/484; 81.6 %), but with comparable detection rates and viral loads between healthy and diarrhoeic pigs; this contrasted with less frequent detection of EV-G in boars (4/45; 8.9 %). EV was most frequently detected in pigs ≤ 14 weeks old (∼95 %) and declined in older pigs. Infections with EV-G1 and EV-G6 were most frequent, whilst less commonly detected types included EV-G3, EV-G4 and EV-G8–EV-G11, and five new types (EV-G12–EV-G16). In contrast, kobuvirus infection frequency was significantly higher in diarrhoeic pigs (40.9 versus 27.6 %; P = 0.01). Kobuviruses also showed contrasting epizootiologies and age associations; a higher prevalence was found in boars (42 %) compared with domestic pigs (29 %), with the highest infection frequency amongst pigs >52 weeks old. Although genetically diverse, all kobuviruses identified belonged to the species Aichivirus C. In summary, this study confirms infection with EV-G was endemic in Vietnamese domestic pigs and exhibits high genetic diversity and extensive inter-type recombination. PMID:26653281

[Eye stress from work with visual screens].

PubMed

Läubli, T; Hünting, W; Grandjean, E

1980-09-01

Four groups of office tasks were studied: Data entry terminals, conversational terminals, traditional office work and typing. Eye impairments are observed in every group of office employees, but the impairments are more frequent in VDU operators. The impairments persist during leisure time. High luminance contrasts between screen and source document are associated with an increase of eye troubles. Increased oscillating luminance of characters is associated with lower visual acuity, with a higher incidence of subjective and objective symptoms of eye irritation including more frequent use of eye drops.

Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome

PubMed Central

Rice, Gillian ; Patrick, Teresa ; Parmar, Rekha ; Taylor, Claire F. ; Aeby, Alec ; Aicardi, Jean ; Artuch, Rafael ; Montalto, Simon Attard ; Bacino, Carlos A. ; Barroso, Bruno ; Baxter, Peter ; Benko, Willam S. ; Bergmann, Carsten ; Bertini, Enrico ; Biancheri, Roberta ; Blair, Edward M. ; Blau, Nenad ; Bonthron, David T. ; Briggs, Tracy ; Brueton, Louise A. ; Brunner, Han G. ; Burke, Christopher J. ; Carr, Ian M. ; Carvalho, Daniel R. ; Chandler, Kate E. ; Christen, Hans-Jürgen ; Corry, Peter C. ; Cowan, Frances M. ; Cox, Helen ; D’Arrigo, Stefano ; Dean, John ; De Laet, Corinne ; De Praeter, Claudine ; Déry, Catherine ; Ferrie, Colin D. ; Flintoff, Kim ; Frints, Suzanna G. M. ; Garcia-Cazorla, Angels ; Gener, Blanca ; Goizet, Cyril ; Goutières, Françoise ; Green, Andrew J. ; Guët, Agnès ; Hamel, Ben C. J. ; Hayward, Bruce E. ; Heiberg, Arvid ; Hennekam, Raoul C. ; Husson, Marie ; Jackson, Andrew P. ; Jayatunga, Rasieka ; Jiang, Yong-Hui ; Kant, Sarina G. ; Kao, Amy ; King, Mary D. ; Kingston, Helen M. ; Klepper, Joerg ; van der Knaap, Marjo S. ; Kornberg, Andrew J. ; Kotzot, Dieter ; Kratzer, Wilfried ; Lacombe, Didier ; Lagae, Lieven ; Landrieu, Pierre Georges ; Lanzi, Giovanni ; Leitch, Andrea ; Lim, Ming J. ; Livingston, John H. ; Lourenco, Charles M. ; Lyall, E. G. Hermione ; Lynch, Sally A. ; Lyons, Michael J. ; Marom, Daphna ; McClure, John P. ; McWilliam, Robert ; Melancon, Serge B. ; Mewasingh, Leena D. ; Moutard, Marie-Laure ; Nischal, Ken K. ; Østergaard, John R. ; Prendiville, Julie ; Rasmussen, Magnhild ; Rogers, R. Curtis ; Roland, Dominique ; Rosser, Elisabeth M. ; Rostasy, Kevin ; Roubertie, Agathe ; Sanchis, Amparo ; Schiffmann, Raphael ; Scholl-Bürgi, Sabine ; Seal, Sunita ; Shalev, Stavit A. ; Corcoles, C. Sierra ; Sinha, Gyan P. ; Soler, Doriette ; Spiegel, Ronen ; Stephenson, John B. P. ; Tacke, Uta ; Tan, Tiong Yang ; Till, Marianne ; Tolmie, John L. ; Tomlin, Pam ; Vagnarelli, Federica ; Valente, Enza Maria ; Van Coster, Rudy N. A. ; Van der Aa, Nathalie ; Vanderver, Adeline ; Vles, Johannes S. H. ; Voit, Thomas ; Wassmer, Evangeline ; Weschke, Bernhard ; Whiteford, Margo L. ; Willemsen, Michel A. A. ; Zankl, Andreas ; Zuberi, Sameer M. ; Orcesi, Simona ; Fazzi, Elisa ; Lebon, Pierre ; Crow, Yanick J. 

2007-01-01

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation–positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. PMID:17846997

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

PubMed

Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A; Barroso, Bruno; Baxter, Peter; Benko, Willam S; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M; Blau, Nenad; Bonthron, David T; Briggs, Tracy; Brueton, Louise A; Brunner, Han G; Burke, Christopher J; Carr, Ian M; Carvalho, Daniel R; Chandler, Kate E; Christen, Hans-Jurgen; Corry, Peter C; Cowan, Frances M; Cox, Helen; D'Arrigo, Stefano; Dean, John; De Laet, Corinne; De Praeter, Claudine; Dery, Catherine; Ferrie, Colin D; Flintoff, Kim; Frints, Suzanna G M; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J; Guet, Agnes; Hamel, Ben C J; Hayward, Bruce E; Heiberg, Arvid; Hennekam, Raoul C; Husson, Marie; Jackson, Andrew P; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G; Kao, Amy; King, Mary D; Kingston, Helen M; Klepper, Joerg; van der Knaap, Marjo S; Kornberg, Andrew J; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J; Livingston, John H; Lourenco, Charles M; Lyall, E G Hermione; Lynch, Sally A; Lyons, Michael J; Marom, Daphna; McClure, John P; McWilliam, Robert; Melancon, Serge B; Mewasingh, Leena D; Moutard, Marie-Laure; Nischal, Ken K; Ostergaard, John R; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R Curtis; Roland, Dominique; Rosser, Elisabeth M; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Burgi, Sabine; Seal, Sunita; Shalev, Stavit A; Corcoles, C Sierra; Sinha, Gyan P; Soler, Doriette; Spiegel, Ronen; Stephenson, John B P; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; Van Coster, Rudy N A; Van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S H; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L; Willemsen, Michel A A; Zankl, Andreas; Zuberi, Sameer M; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J

2007-10-01

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.

Screening for Cancer by Residents in an Internal Medicine Program.

ERIC Educational Resources Information Center

Lynch, Garrett R.; Prout, Marianne N.

1986-01-01

A study of cancer screening by internal medicine residents in an inner-city clinic revealed that screening was more frequent for male patients, and breast examinations and Pap smears were performed on less than a third of female patients, suggesting a need for more intensive early-detection education of residents. (MSE)

A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53

PubMed Central

Bechill, John; Zhong, Rong; Zhang, Chen; Solomaha, Elena

2016-01-01

p53 function is frequently inhibited in cancer either through mutations or by increased degradation via MDM2 and/or E6AP E3-ubiquitin ligases. Most agents that restore p53 expression act by binding MDM2 or E6AP to prevent p53 degradation. However, fewer compounds directly bind to and activate p53. Here, we identified compounds that shared a core structure that bound p53, caused nuclear localization of p53 and caused cell death. To identify these compounds, we developed a novel cell-based screen to redirect p53 degradation to the Skip-Cullin-F-box (SCF) ubiquitin ligase complex in cells expressing high levels of p53. In a multiplexed assay, we coupled p53 targeted degradation with Rb1 targeted degradation in order to identify compounds that prevented p53 degradation while not inhibiting degradation through the SCF complex or other proteolytic machinery. High-throughput screening identified several leads that shared a common 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that stabilized p53. Surface plasmon resonance analysis indicated that these compounds bound p53 with a KD of 200 ± 52 nM. Furthermore, these compounds increased p53 nuclear localization and transcription of the p53 target genes PUMA, BAX, p21 and FAS in cancer cells. Although p53-null cells had a 2.5±0.5-fold greater viability compared to p53 wild type cells after treatment with core compounds, loss of p53 did not completely rescue cell viability suggesting that compounds may target both p53-dependent and p53-independent pathways to inhibit cell proliferation. Thus, we present a novel, cell-based high-throughput screen to identify a 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that bound to p53 and increased p53 activity in cancer cells. These compounds may serve as anti-neoplastic agents in part by targeting p53 as well as other potential pathways. PMID:27124407

The frequent shift to intermediate flora in preterm delivery cases after abnormal vaginal flora screening

PubMed Central

Honda, Hiroshi; Yokoyama, Takanori; Akimoto, Yumiko; Tanimoto, Hirotoshi; Teramoto, Mitsue; Teramoto, Hideki

2014-01-01

The effect of screening and treatment for abnormal vaginal flora on the reduction of preterm deliveries remains controversial. We evaluated whether this screening and treatment reduces the preterm delivery rate for general-population pregnant women. Pregnant women of the Intervention group (n = 574) underwent the screening test and the treatment of vaginal metronidazole during the early second trimester, and those of the Control group (n = 1,161) did not. We compared the preterm delivery rate between these two groups. We also compared the profiles of vaginal flora of the preterm delivery cases with those of the pregnant women with a normal course. There was no significant difference in the preterm delivery rate between these two groups. However, in the preterm delivery cases, a frequent shift to intermediate flora was observed not before but after the screening in the Intervention group. This shift may explain why most of the previous studies failed in regard to the prevention of preterm deliveries. PMID:24762852

Masculinity, Racism, Social Support, and Colorectal Cancer Screening Uptake Among African American Men: A Systematic Review.

PubMed

Rogers, Charles R; Mitchell, Jamie A; Franta, Gabriel J; Foster, Margaret J; Shires, Deirdre

2017-09-01

Colorectal cancer (CRC) is highly preventable when CRC screening is utilized, yet CRC screening completion among African American men is relatively low and their mortality rates remain 50% higher juxtaposed to their White counterparts. Since a growing body of literature indicates masculinity, racism, and social support each have strong influences on CRC screening uptake, this systematic review examined the connections between these three sociocultural factors and CRC screening uptake among African American men. Potential studies were retrieved from MEDLINE, CINAHL, EMBASE, and PsycINFO. Cited reference searching for the final sample was employed to identify and assess additional studies for inclusion using Scopus. The methodological quality of the reviewed evidence was also evaluated. Nineteen studies met inclusion/exclusion criteria. Thirteen studies employed nonexperimental research designs; a quasi-experimental design was present in four, and two utilized experimental designs. Studies were published between 2000 and 2014; the majority between 2009 and 2013. Social support was most frequently addressed (84%) while masculinity and racism were equally studied with paucity (11%) for their influence on CRC screening. After evaluating conceptual and methodological characteristics of the studies, 42% fell below average in quality and rigor. The need for increased attention to the sociocultural correlates of CRC screening for African American men are highlighted in this systematic review, and important recommendations for research and practice are provided. Alongside a call for more rigorous research, further research examining the influence of masculinity and racism on CRC screening completion among African American men is warranted.

Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Banks, Kathryn; Gaviglio, Amy; Hietala, Amy; McCann, Mark; Thomas, William

2012-11-01

Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known. This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols. Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average). In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.

Examining the association between possessing a regular source of healthcare and adherence with cancer screenings among Haitian households in Little Haiti, Miami-Dade County, Florida

PubMed Central

Pang, Hauchie; Cataldi, Mariel; Allseits, Emmanuelle; Ward-Peterson, Melissa; de la Vega, Pura Rodríguez; Castro, Grettel; Acuña, Juan Manuel

2017-01-01

Abstract Immigrant minorities regularly experience higher incidence and mortality rates of cancer. Frequently, a variety of social determinants create obstacles for those individuals to get the screenings they need. This is especially true for Haitian immigrants, a particularly vulnerable immigrant population in South Florida, who have been identified as having low cancer screening rates. While Haitian immigrants have some of the lowest cancer screening rates in the country, there is little existing literature that addresses barriers to cancer screenings among the population of Little Haiti in Miami-Dade County, Florida. The objective of this study was to evaluate the association between having a regular source of healthcare and adherence to recommended cancer screenings in the Little Haiti population of Miami. This secondary analysis utilized data collected from a random-sample, population-based household survey conducted from November 2011 to December 2012 among a geographic area approximating Little Haiti in Miami-Dade County, Florida. A total of 421 households identified as Haitian. The main exposure of interest was whether households possessed a regular source of care. Three separate outcomes were considered: adherence with colorectal cancer screening, mammogram adherence, and Pap smear adherence. Analysis was limited to households who met the age criteria for each outcome of interest. Bivariate associations were examined using the chi square test and Fisher exact test. Binary logistic regression was used to estimate unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). After adjusting for the head of household's education and household insurance status, households without a regular source of care were significantly less likely to adhere with colorectal cancer screening (OR = 0.33; 95% CI: 0.14–0.80) or mammograms (OR = 0.28; 95% CI: 0.11–0.75). Households with insurance coverage gaps were significantly less likely to adhere with mammograms (OR = 0.40; 95% CI: 0.17–0.97) or Pap smears (OR = 0.28; 95% CI: 0.13–0.58). Our study explored adherence with multiple cancer screenings. We found a strong association between possessing a regular source of care and adherence with colorectal cancer screening and mammogram adherence. Targeted approaches to improving access to regular care may improve adherence to cancer screening adherence among this unique immigrant population. PMID:28796056

Analysis of three strategies to increase screening coverage for cervical cancer in the general population of women aged 60 to 70 years: the CRICERVA study

PubMed Central

2014-01-01

Background Cervical cancer is a frequently diagnosed cancer in women worldwide. Despite having easy preventive and therapeutic approaches, it is an important cause of mortality among women. Methods The CRICERVA study is a cluster clinical trial which assigned one of three interventions to the target population registered in Cerdanyola, Barcelona. Among the 5,707 resident women aged 60 to 70 years in the study area, women with no record of cervical cytology over the last three years were selected. The study included four arms: three interventions all including a pre-assigned date for screening visit and i) personalized invitation letter; ii) adding to i) an informative leaflet; and, iii) in addition to ii) a personalized appointment reminder phone call, and iv) no specific action taken (control group). Participants were offered a personal interview about social-demographic characteristics and about screening attitudes. Cervical cytology and HPV DNA test (HC2) were offered as screening tests. In the case of screening positive in any of these tests, the women were followed up until a full diagnosis could be obtained. The effect size of each study arm was estimated as the absolute gain in coverage between the original coverage and the final coverage. Results From the intervention groups (4,775 women), we identified 3,616 who were not appropriately screened, of which 2,560 women answered the trial call and 1,376 were amenable to screening. HPV was tested in 920 women and cervical cytology in all 1,376. Overall, there was an absolute gain in coverage of 28.8% in the intervention groups compared to 6% in the control group. Coverage increased from 51.2% to 76.0% in strategy i); from 47.4% to 79.0% in strategy ii) and from 44.5% to 74.6% in strategy iii). Lack of information about the relevance of screening was the most important factor for not attending the screening program. Conclusions The study confirms that actively contacting women and including a date for a screening visit, notably increased participation in the screening program. Efforts to improve health education in preventative activities are warranted. Trial registration Clinical Trials.gov Identifier NCT01373723. Registered 14 June 2011. PMID:25026889

Ecological Soil Screening Level

EPA Pesticide Factsheets

The Eco-SSL derivation process is used to derive a set of risk-based ecological soil screening levels (Eco-SSLs) for many of the soil contaminants that are frequently of ecological concern for plants and animals at hazardous waste sites.

[New guidelines in regard to cervical cancer screening].

PubMed

Vargas-Hernández, Víctor Manuel; Acosta-Altamirano, Gustavo; Moreno-Eutimio, Mario Adán; Vargas-Aguilar, Víctor Manuel

2014-01-01

Cancer screening programs have been successful in reducing the incidence and mortality due to cervical cancer. For more than a decade, the human papillomavirus test has been recommended as part of these programs, however, Pap tests is not currently recommended for women 65 years of age who participated adequately in screening programs, continuing with these screening programs is not needed. Screening programs will be different in special populations at greatest risk where tests are frequently needed or use of alternative methods.

A review of current practices to increase Chlamydia screening in the community--a consumer-centred social marketing perspective.

PubMed

Phillipson, Lyn; Gordon, Ross; Telenta, Joanne; Magee, Chris; Janssen, Marty

2016-02-01

Chlamydia trachomatis is one of the most frequently reported sexually transmitted infections (STI) in Australia, the UK and Europe. Yet, rates of screening for STIs remain low, especially in younger adults. To assess effectiveness of Chlamydia screening interventions targeting young adults in community-based settings, describe strategies utilized and assess them according to social marketing benchmark criteria. A systematic review of relevant literature between 2002 and 2012 in Medline, Web of Knowledge, PubMed, Scopus and the Cumulative Index to Nursing and Allied Health was undertaken. Of 18 interventions identified, quality of evidence was low. Proportional screening rates varied, ranging from: 30.9 to 62.5% in educational settings (n = 4), 4.8 to 63% in media settings (n = 6) and from 5.7 to 44.5% in other settings (n = 7). Assessment against benchmark criteria found that interventions incorporating social marketing principles were more likely to achieve positive results, yet few did this comprehensively. Most demonstrated customer orientation and addressed barriers to presenting to a clinic for screening. Only one addressed barriers to presenting for treatment after a positive result. Promotional messages typically focused on providing facts and accessing a testing kit. Risk assessment tools appeared to promote screening among higher risk groups. Few evaluated treatment rates following positive results; therefore, impact of screening on treatment rates remains unknown. Future interventions should consider utilizing a comprehensive social marketing approach, using formative research to increase insight and segmentation and tailoring of screening interventions. Easy community access to both screening and treatment should be prioritized. © 2015 John Wiley & Sons Ltd.

Misuse of Prescribed Stimulant Medication for ADHD and Associated Patterns of Substance Use: Preliminary Analysis Among College Students

PubMed Central

Sepúlveda, Dalissa R.; Thomas, Lisl M.; McCabe, Sean Esteban; Cranford, James A.; Boyd, Carol J.; Teter, Christian J.

2012-01-01

Objectives To explore the prevalence and characteristics associated with college students who misuse their prescribed stimulants for attention-deficit hyperactivity disorder (ADHD) and examine diversion and substance use behaviors as a function of misuse. Methods Cohort of 55 past-year prescribed stimulant users was identified from a random sample (n = 1738) at a large Midwestern research university following the self-administration of a web-based survey. An index was created to assess misuse of prescribed stimulants (i.e., Misuse Index). Results Of 55 college students who reported past-year use of prescribed stimulants for ADHD, 22 (40%) endorsed at least one item on the misuse index. The most frequently endorsed misuse items were used too much (36%), self-reported misuse (19%), and intentionally used with alcohol or other drugs (19%). Misusers of prescribed stimulant medication were more likely to report cigarette smoking (p = 0.022), binge drinking (p = 0.022), illicit use of cocaine (p = 0.032), and screen positive on the Drug Abuse Screening test (DAST-10) criteria (p = 0.002). The bivariate odds ratio for the DAST-10 findings was 8.4 (95% CI: 2.0–34.6). Diversion of prescribed stimulants was common (36%) and occurred more frequently among stimulant misusers (57%; p = 0.008). Conclusion There is a strong relationship between misuse of prescribed stimulants for ADHD and substance use behaviors, as well as other deleterious behaviors such as diversion. These findings suggest the need for close screening, assessment, and therapeutic monitoring of medication use in the college population. PMID:22095577

Specific Location of Disc Hemorrhage is Linked to Nerve Fiber Layer Defects.

PubMed

Yoo, Young Cheol; Kim, Joon Mo; Park, Han Seok; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Park, Ki Ho; Chang, Robert T

2017-06-01

To investigate the relationship between retinal nerve fiber layer (RNFL) defects and the quadrant and proximal location of disc hemorrhages (DHs) in a large population examined for health screening. A total of 168,044 subjects older than 20 years underwent a single screening ophthalmic examination with color fundus photography as part of a comprehensive health screening program. The presence and location of DHs and RNFL defects were assessed. The DH locations were defined according to the quadrant location (inferotemporal, superotemporal, inferonasal, or superonasal) and the most proximal end of DHs relative to the disc center (cup base, cup margin, disc rim, or extrapapillary region). Using these two location descriptors as independent variables, a logistic regression analysis was conducted to explore the effects of DH location on RNFL defects. Two hundred twenty-six eyes had DH and 120 (53.1%) of them had RNFL defects. After adjusting for proximal location, DHs located in the inferotemporal quadrant accompanied RFNL defects 12 times more frequently than those in the superonasal quadrant (odds ratio [OR], 11.81; P = .004). Conversely, after adjusting for quadrant location, the ORs for an associated RNFL defect were 3.73 (P < .001), 16.54 (P < .001), and 8.91 (P = .002) for DHs with the proximal end at the disc rim, cup margin, and cup base, respectively. Among the four quadrants and four proximal locations, DHs were identified most frequently in the inferotemporal quadrant and outside the disc, respectively. Some DH locations, such as the inferotemporal quadrant and the cup margin, were associated with RNFL defects, whereas others were not.

Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

PubMed

Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

2013-04-01

Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies

PubMed Central

2017-01-01

A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell–wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure–activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties. PMID:29148755

Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1.

PubMed

Vlaming, Hanneke; Molenaar, Thom M; van Welsem, Tibor; Poramba-Liyanage, Deepani W; Smith, Desiree E; Velds, Arno; Hoekman, Liesbeth; Korthout, Tessy; Hendriks, Sjoerd; Altelaar, A F Maarten; van Leeuwen, Fred

2016-12-06

Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel. Screening of a barcoded yeast knock-out collection for regulators of histone H3K79 methylation by Dot1 identified all known regulators as well as novel players and processes. These include histone deposition, homologous recombination, and adenosine kinase, which influences the methionine cycle. Gcn5, the acetyltransferase within the SAGA complex, was found to regulate histone methylation and H2B ubiquitination. The concept of Epi-ID is widely applicable and can be readily applied to other chromatin features.

Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1

PubMed Central

Vlaming, Hanneke; Molenaar, Thom M; van Welsem, Tibor; Poramba-Liyanage, Deepani W; Smith, Desiree E; Velds, Arno; Hoekman, Liesbeth; Korthout, Tessy; Hendriks, Sjoerd; Maarten Altelaar, AF; van Leeuwen, Fred

2016-01-01

Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel. Screening of a barcoded yeast knock-out collection for regulators of histone H3K79 methylation by Dot1 identified all known regulators as well as novel players and processes. These include histone deposition, homologous recombination, and adenosine kinase, which influences the methionine cycle. Gcn5, the acetyltransferase within the SAGA complex, was found to regulate histone methylation and H2B ubiquitination. The concept of Epi-ID is widely applicable and can be readily applied to other chromatin features. DOI: http://dx.doi.org/10.7554/eLife.18919.001 PMID:27922451

Safety pharmacology investigations on the nervous system: An industry survey.

PubMed

Authier, Simon; Arezzo, Joseph; Delatte, Marcus S; Kallman, Mary-Jeanne; Markgraf, Carrie; Paquette, Dominique; Pugsley, Michael K; Ratcliffe, Sian; Redfern, William S; Stevens, Joanne; Valentin, Jean-Pierre; Vargas, Hugo M; Curtis, Michael J

2016-01-01

The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address non-clinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of radiography as a screening method for detection and characterisation of congenital vertebral malformations in dogs.

PubMed

Brocal, Josep; De Decker, Steven; José-López, Roberto; Guevar, Julien; Ortega, Maria; Parkin, Tim; Ter Haar, Gert; Gutierrez-Quintana, Rodrigo

2018-05-19

Congenital vertebral malformations (CVM) are common in brachycephalic 'screw-tailed' dogs; they can be associated with neurological deficits and a genetic predisposition has been suggested. The purpose of this study was to evaluate radiography as a screening method for congenital thoracic vertebral malformations in brachycephalic 'screw-tailed' dogs by comparing it with CT. Forty-nine dogs that had both radiographic and CT evaluations of the thoracic vertebral column were included. Three observers retrospectively reviewed the images independently to detect CVMs. When identified, they were classified according to a previously published radiographic classification scheme. A CT consensus was then reached. All observers identified significantly more affected vertebrae when evaluating orthogonal radiographic views compared with lateral views alone; and more affected vertebrae with the CT consensus compared with orthogonal radiographic views. Given the high number of CVMs per dog, the number of dogs classified as being CVM free was not significantly different between CT and radiography. Significantly more midline closure defects were also identified with CT compared with radiography. Malformations classified as symmetrical or ventral hypoplasias on radiography were frequently classified as ventral and medial aplasias on CT images. Our results support that CT is better than radiography for the classification of CVMs and this will be important when further evidence of which are the most clinically relevant CVMs is identified. These findings are of particular importance for designing screening schemes of CVMs that could help selective breeding programmes based on phenotype and future studies. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hearing Loss in HIV-Infected Children in Lilongwe, Malawi

PubMed Central

Hrapcak, Susan; Kuper, Hannah; Bartlett, Peter; Devendra, Akash; Makawa, Atupele; Kim, Maria; Kazembe, Peter; Ahmed, Saeed

2016-01-01

Introduction With improved access to antiretroviral therapy (ART), HIV infection is becoming a chronic illness. Preliminary data suggest that HIV-infected children have a higher risk of disabilities, including hearing impairment, although data are sparse. This study aimed to estimate the prevalence and types of hearing loss in HIV-infected children in Lilongwe, Malawi. Methods This was a cross-sectional survey of 380 HIV-infected children aged 4–14 years attending ART clinic in Lilongwe between December 2013-March 2014. Data was collected through pediatric quality of life and sociodemographic questionnaires, electronic medical record review, and detailed audiologic testing. Hearing loss was defined as >20 decibels hearing level (dBHL) in either ear. Predictors of hearing loss were explored by regression analysis generating age- and sex-adjusted odds ratios. Children with significant hearing loss were fitted with hearing aids. Results Of 380 patients, 24% had hearing loss: 82% conductive, 14% sensorineural, and 4% mixed. Twenty-one patients (23% of those with hearing loss) were referred for hearing aid fitting. There was a higher prevalence of hearing loss in children with history of frequent ear infections (OR 7.4, 4.2–13.0) and ear drainage (OR 6.4, 3.6–11.6). Hearing loss was linked to history of WHO Stage 3 (OR 2.4, 1.2–4.5) or Stage 4 (OR 6.4, 2.7–15.2) and history of malnutrition (OR 2.1, 1.3–3.5), but not to duration of ART or CD4. Only 40% of caregivers accurately perceived their child’s hearing loss. Children with hearing impairment were less likely to attend school and had poorer emotional (p = 0.02) and school functioning (p = 0.04). Conclusions There is an urgent need for improved screening tools, identification and treatment of hearing problems in HIV-infected children, as hearing loss was common in this group and affected school functioning and quality of life. Clear strategies were identified for prevention and treatment, since most hearing loss was conductive in nature, likely due to frequent ear infections, and many children with hearing loss qualified for hearing aids. Screening strategies need to be developed and tested since caregivers were not reliable at identifying hearing loss, and often mis-identified children with normal hearing as having hearing loss. Children with frequent ear infections, ear drainage, TB, severe HIV disease, or low BMI should receive more frequent ear assessments and hearing evaluations. PMID:27551970

Navigation in the electronic health record: A review of the safety and usability literature.

PubMed

Roman, Lisette C; Ancker, Jessica S; Johnson, Stephen B; Senathirajah, Yalini

2017-03-01

Inefficient navigation in electronic health records has been shown to increase users' cognitive load, which may increase potential for errors, reduce efficiency, and increase fatigue. However, navigation has received insufficient recognition and attention in the electronic health record (EHR) literature as an independent construct and contributor to overall usability. Our aims in this literature review were to (1) assess the prevalence of navigation-related topics within the EHR usability and safety research literature, (2) categorize types of navigation actions within the EHR, (3) capture relationships between these navigation actions and usability principles, and (4) collect terms and concepts related to EHR navigation. Our goal was to improve access to navigation-related research in usability. We applied scoping literature review search methods with the assistance of a reference librarian to identify articles published since 1996 that reported evaluation of the usability or safety of an EHR user interface via user test, analytic methods, or inspection methods. The 4336 references collected from MEDLINE, EMBASE, Engineering Village, and expert referrals were de-duplicated and screened for relevance, and navigation-related concepts were abstracted from the 21 articles eligible for review using a standard abstraction form. Of the 21 eligible articles, 20 (95%) mentioned navigation in results and discussion of usability evaluations. Navigation between pages of the EHR was the more frequently documented type of navigation (86%) compared to navigation within a single page (14%). Navigation actions (e.g., scrolling through a medication list) were frequently linked to specific usability heuristic violations, among which flexibility and efficiency of use, recognition rather than recall, and error prevention were most common. Discussion of navigation was prevalent in results across all types of evaluation methods among the articles reviewed. Navigating between multiple screens was frequently identified as a usability barrier. The lack of standard terminology created some challenges to identifying and comparing articles. We observed that usability researchers are frequently capturing navigation-related issues even in articles that did not explicitly state navigation as a focus. Capturing and synthesizing the literature on navigation is challenging because of the lack of uniform vocabulary. Navigation is a potential target for normative recommendations for improved interaction design for safer systems. Future research in this domain, including development of normative recommendations for usability design and evaluation, will be facilitated by development of a standard terminology for describing EHR navigation. Copyright © 2017 Elsevier Inc. All rights reserved.

The prevalence and nature of intellectual disability in Norwegian prisons.

PubMed

Søndenaa, E; Rasmussen, K; Palmstierna, T; Nøttestad, J

2008-12-01

The objective of the study was to calculate the prevalence of inmates with intellectual disabilities (ID), and identify historical, medical and criminological characteristics of a certain impact. A random sample of 143 inmates from a Norwegian prison cross sectional sample was studied. The Hayes Ability Screening Index (HASI) was validated with the Wechsler Abbreviated Scale of Intelligence (WASI). The prevalence of inmates with ID, IQ < 70, was 10.8%. Some essential characteristics of inmates with ID were more frequent medication for mental disorders, a higher number of imprisonments, less drug abuse and less education than the other inmates. The results indicated that the HASI is a valid tool for screening of ID for the Norwegian inmates. The prevalence of ID in Norwegian inmates is significant, measured by WASI and HASI. Identification, rehabilitation and care, concerning an intellectual handicap, are mostly absent in the Norwegian criminal justice system.

Sex Trafficking Assessment and Resources (STAR) for Pediatric Attendings in Rhode Island.

PubMed

Moore, Jessica L; Baird, Grayson; Goldberg, Amy P

2016-09-01

Domestic minor sex trafficking (DMST) victims have unique medical and mental health needs and present frequently for medical attention. Little is known about the reported training, screening, comfort and knowledge of DMST among pediatricians in Rhode Island who likely encounter these patient victims without knowing. An anonymous electronic survey sent to Rhode Island Hospital staff physicians from November 2014 through January 2015. Of the 109 participants, the majority reported no training, screened no patients for DMST in the past year, did not know any resources available and had limited knowledge and comfort with this pediatric patient population. Rhode Island pediatricians of various specialties do not feel adequately prepared to identify and respond to a DMST patient population. These findings inform the need for increased training and education on DMST in our medical community. [Full article available at http://rimed.org/rimedicaljournal-2016-09.asp, free with no login].

Nasal, oral and rectal microbiota of Black lion tamarins (Leontopithecus chrysopygus)

PubMed Central

Carvalho, Vania M.; Vanstreels, Ralph E.T.; Paula, Cátia D.; Kolesnikovas, Cristiane K.M.; Ramos, Maria Christina C.; Coutinho, Selene D.; Martins, Cristiana S.; Pissinatti, Alcides; Catão-Dias, José L.

2014-01-01

Black lion tamarins (Leontopithecus chrysopygus) are endangered callithrichids. Their conservation may require future translocations or reintroductions; however these approaches involve risks of pathogen introduction in the environment and stress-related opportunistic infections in these animals. In order to screen for opportunistic and potential pathogenic bacterial and fungal microbiota, ten free-ranging and ten captive Black lion tamarins were studied and the results compared. Nasal, oral and rectal swabs were collected and cultured for aerobic and facultative anaerobic bacteria and fungi, and a total 203 bacterial and 84 fungal isolates were obtained. Overall, the most frequent organisms were Staphylococcus spp., Bacillus spp., Candida spp. and Aspergillus spp. Microbiota of free-ranging and captive animals were similar in composition. A number of potentially pathogenic organisms were identified, emphasizing the importance of microbiological screening in future translocation or reintroduction conservation management programs. PMID:25763064

Analysis of EPA's endocrine screening battery and recommendations for further review.

PubMed

Schapaugh, Adam W; McFadden, Lisa G; Zorrilla, Leah M; Geter, David R; Stuchal, Leah D; Sunger, Neha; Borgert, Christopher J

2015-08-01

EPA's Endocrine Disruptor Screening Program Tier 1 battery consists of eleven assays intended to identify the potential of a chemical to interact with the estrogen, androgen, thyroid, or steroidogenesis systems. We have collected control data from a subset of test order recipients from the first round of screening. The analysis undertaken herein demonstrates that the EPA should review all testing methods prior to issuing further test orders. Given the frequency with which certain performance criteria were violated, a primary focus of that review should consider adjustments to these standards to better reflect biological variability. A second focus should be to provide detailed, assay-specific direction on when results should be discarded; no clear guidance exists on the degree to which assays need to be re-run for failing to meet performance criteria. A third focus should be to identify permissible differences in study design and execution that have a large influence on endpoint variance. Experimental guidelines could then be re-defined such that endpoint variances are reduced and performance criteria are violated less frequently. It must be emphasized that because we were restricted to a subset (approximately half) of the control data, our analyses serve only as examples to underscore the importance of a detailed, rigorous, and comprehensive evaluation of the performance of the battery. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Virtual screening using the ligand ZINC database for novel lipoxygenase-3 inhibitors.

PubMed

Monika; Kour, Janmeet; Singh, Kulwinder

2013-01-01

The leukotrienes constitute a group of arachidonic acid-derived compounds with biologic activities suggesting important roles in inflammation and immediate hypersensitivity. Epidermis-type lipoxygenase-3 (ALOXE3), a distinct subclass within the multigene family of mammalian lipoxygenases, is a novel isoenzyme involved in the metabolism of leukotrienes and plays a very important role in skin barrier functions. Lipoxygenase selective inhibitors such as azelastine and zileuton are currently used to reduce inflammatory response. Nausea, pharyngolaryngeal pain, headache, nasal burning and somnolence are the most frequently reported adverse effects of these drugs. Therefore, there is still a need to develop more potent lipoxygenase inhibitors. In this paper, we report the screening of various compounds from the ZINC database (contains over 21 million compounds) using the Molegro Virtual Docker software against the ALOXE3 protein. Screening was performed using molecular constraints tool to filter compounds with physico-chemical properties similar to the 1N8Q bound ligand protocatechuic acid. The analysis resulted in 4319 Lipinski compliant hits which are docked and scored to identify structurally novel ligands that make similar interactions to those of known ligands or may have different interactions with other parts of the binding site. Our screening approach identified four molecules ZINC84299674; ZINC76643455; ZINC84299122 & ZINC75626957 with MolDock score of -128.901, -120.22, -116.873 & - 102.116 kcal/mol, respectively. Their energy scores were better than the 1N8Q bound co-crystallized ligand protocatechuic acid (with MolDock score of -77.225 kcal/mol). All the ligands were docked within the binding pocket forming interactions with amino acid residues.

[Comparative evaluation of information products regarding cancer screening of German-speaking cancer organizations].

PubMed

Hofmann, Julia; Kien, Christina; Gartlehner, Gerald

2015-01-01

Evidence-based information materials about the pros and cons of cancer screening are important sources for men and women to decide for or against cancer screening. The aim of this paper was to compare recommendations from different cancer institutions in German-speaking countries (Austria, Germany, and Switzerland) regarding screening for breast, cervix, colon, and prostate cancer and to assess the quality and development process of patient information materials. Relevant information material was identified through web searches and personal contact with cancer institutions. To achieve our objective, we employed a qualitative approach. The quality of 22 patient information materials was analysed based on established guidance by Bunge et al. In addition, we conducted guided interviews about the process of developing information materials with decision-makers of cancer institutes. Overall, major discrepancies in cancer screening recommendations exist among the Austrian, German, and Swiss cancer institutes. Process evaluation revealed that crucial steps of quality assurance, such as assembling a multi-disciplinary panel, assessing conflicts of interest, or transparency regarding funding sources, have frequently not been undertaken. All information materials had substantial quality deficits in multiple areas. Three out of four institutes issued information materials that met fewer than half of the quality criteria. Most patient information materials of cancer institutes in German-speaking countries are fraught with substantial deficits and do not provide an objective source for patients to be able to make an informed decision for or against cancer screening. Copyright © 2015. Published by Elsevier GmbH.

Performance characterization of a combined material identification and screening algorithm

NASA Astrophysics Data System (ADS)

Green, Robert L.; Hargreaves, Michael D.; Gardner, Craig M.

2013-05-01

Portable analytical devices based on a gamut of technologies (Infrared, Raman, X-Ray Fluorescence, Mass Spectrometry, etc.) are now widely available. These tools have seen increasing adoption for field-based assessment by diverse users including military, emergency response, and law enforcement. Frequently, end-users of portable devices are non-scientists who rely on embedded software and the associated algorithms to convert collected data into actionable information. Two classes of problems commonly encountered in field applications are identification and screening. Identification algorithms are designed to scour a library of known materials and determine whether the unknown measurement is consistent with a stored response (or combination of stored responses). Such algorithms can be used to identify a material from many thousands of possible candidates. Screening algorithms evaluate whether at least a subset of features in an unknown measurement correspond to one or more specific substances of interest and are typically configured to detect from a small list potential target analytes. Thus, screening algorithms are much less broadly applicable than identification algorithms; however, they typically provide higher detection rates which makes them attractive for specific applications such as chemical warfare agent or narcotics detection. This paper will present an overview and performance characterization of a combined identification/screening algorithm that has recently been developed. It will be shown that the combined algorithm provides enhanced detection capability more typical of screening algorithms while maintaining a broad identification capability. Additionally, we will highlight how this approach can enable users to incorporate situational awareness during a response.

Screening for kidney disease in children on World Kidney Day in Jalisco, Mexico.

PubMed

Koshy, Susan M; Garcia-Garcia, Guillermo; Pamplona, Jacob Sandoval; Renoirte-Lopez, Karina; Perez-Cortes, Gustavo; Gutierrez, Ma Luisa Salazar; Hemmelgarn, Brenda; Lloyd, Anita; Tonelli, Marcello

2009-06-01

World Kidney Day (WKD) is intended to raise awareness and increase detection of chronic kidney disease (CKD), but most emphasis is placed on adults rather than children. We examined yield of screening for CKD and hypertension among poor children in Mexico. On WKD (2006, 2007), children (age < 18 years) without known CKD were invited to participate at two screening stations. We measured body mass index (BMI), blood pressure, and serum creatinine, and performed dipstick urinalysis. The Schwartz equation was used to estimate glomerular filtration rate (GFR; reduced GFR defined as < 60 ml/min per 1.73 m(2)). Proteinuria and hematuria were defined by a reading of >or= 1+ protein or blood on dipstick. Hypertension was defined by gender, age, and height-specific norms. In total, 240 children were screened (mean age 8.9 +/- 4.1 years; 44.2% male). Proteinuria and hematuria were detected in 38 (16.1%) and 41 (17.5%), respectively; 15% had BMI > 95th percentile for age. Reduced GFR was detected in four (1.7%) individuals. Systolic hypertension was more prevalent in younger children (age 0-8 years, 19.6%; age 9-13 years, 7.1%; age 14-17 years, 5.3%) suggesting a possible white-coat effect. Hematuria, proteinuria, hypertension and obesity were frequently detected among children in a community based screening program in Mexico. This form of screening might be useful in identifying children with CKD and hypertension in developing nations.

Urine Multi-drug Screening with GC-MS or LC-MS-MS Using SALLE-hybrid PPT/SPE.

PubMed

Lee, Junhui; Park, Jiwon; Go, Ahra; Moon, Heesung; Kim, Sujin; Jung, Sohee; Jeong, Wonjoon; Chung, Heesun

2018-05-14

To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.

Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase.

PubMed

Zhang, Jie; Liu, Hongchuan; Zhu, Kongkai; Gong, Shouzhe; Dramsi, Shaynoor; Wang, Ya-Ting; Li, Jiafei; Chen, Feifei; Zhang, Ruihan; Zhou, Lu; Lan, Lefu; Jiang, Hualiang; Schneewind, Olaf; Luo, Cheng; Yang, Cai-Guang

2014-09-16

Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequent cause of hospital-acquired infection, which manifests as surgical site infections, bacteremia, and sepsis. Due to drug-resistance, prophylaxis of MRSA infection with antibiotics frequently fails or incites nosocomial diseases such as Clostridium difficile infection. Sortase A is a transpeptidase that anchors surface proteins in the envelope of S. aureus, and sortase mutants are unable to cause bacteremia or sepsis in mice. Here we used virtual screening and optimization of inhibitor structure to identify 3-(4-pyridinyl)-6-(2-sodiumsulfonatephenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole and related compounds, which block sortase activity in vitro and in vivo. Sortase inhibitors do not affect in vitro staphylococcal growth yet protect mice against lethal S. aureus bacteremia. Thus, sortase inhibitors may be useful as antiinfective therapy to prevent hospital-acquired S. aureus infection in high-risk patients without the side effects of antibiotics.

Mutations in FUS are the most frequent genetic cause in juvenile sporadic ALS patients of Chinese origin.

PubMed

Zou, Zhang-Yu; Liu, Ming-Sheng; Li, Xiao-Guang; Cui, Li-Ying

2016-01-01

Juvenile onset ALS is a very rare form of motor neuron disease, with the first symptoms of motor neuron degeneration manifested before 25 years of age. Mutations in the alsin (ALS2), senataxin (SETX), and spatacsin (SPG11) genes have been associated with familial ALS with juvenile onset and slow progression, whereas the genetic architecture of sporadic juvenile ALS remains unclear. We screened mutations in C9orf72, SOD1, FUS, TARDBP, ANG, VCP and PFN1 in 16 juvenile sporadic ALS patients. Four cases (25%) carrying FUS mutations and one individual (6%) harbouring a SOD1 mutation were identified. All cases had an aggressive disease course. Our results suggest that FUS mutations are the most frequent genetic cause in early-onset sporadic ALS patients of Chinese origin. Genetic testing of FUS should be performed in early-onset ALS patients especially those with an aggressive disease course.

Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs.

PubMed

Kamola, Piotr J; Maratou, Klio; Wilson, Paul A; Rush, Kay; Mullaney, Tanya; McKevitt, Tom; Evans, Paula; Ridings, Jim; Chowdhury, Probash; Roulois, Aude; Fairchild, Ann; McCawley, Sean; Cartwright, Karen; Gooderham, Nigel J; Gant, Timothy W; Moores, Kitty; Hughes, Stephen A; Edbrooke, Mark R; Clark, Kenneth; Parry, Joel D

2017-09-15

Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs. To rank ASOs based on their effect on the liver, we have developed an acute screen in the mouse that can be applied early in the drug development cycle. A single-dose (3-day) screen with streamlined endpoints (i.e., plasma transaminase levels and liver weights) was observed to be predictive of ASO hepatotoxicity ranking established based on a repeat-dose (15 day) study. Furthermore, to study the underlying mechanisms of liver toxicity, we applied transcriptome profiling and pathway analyses and show that adverse in vivo liver phenotypes correlate with the number of potent, hybridization-mediated off-target effects (OTEs). We propose that a combination of in silico OTE predictions, streamlined in vivo hepatotoxicity screening, and a transcriptome-wide selectivity screen is a valid approach to identifying and progressing safer compounds. Copyright © 2017 GSK R&D. Published by Elsevier Inc. All rights reserved.

Primary care patients reporting concerns about their gambling frequently have other co-occurring lifestyle and mental health issues

PubMed Central

Goodyear-Smith, Felicity; Arroll, Bruce; Kerse, Ngaire; Sullivan, Sean; Coupe, Nicole; Tse, Samson; Shepherd, Robin; Rossen, Fiona; Perese, Lana

2006-01-01

Background Problem gambling often goes undetected by family physicians but may be associated with stress-related medical problems as well as mental disorders and substance abuse. Family physicians are often first in line to identify these problems and to provide a proper referral. The aim of this study was to compare a group of primary care patients who identified concerns with their gambling behavior with the total population of screened patients in relation to co-morbidity of other lifestyle risk factors or mental health issues. Methods This is a cross sectional study comparing patients identified as worrying about their gambling behavior with the total screened patient population for co morbidity. The setting was 51 urban and rural New Zealand practices. Participants were consecutive adult patients per practice (N = 2,536) who completed a brief multi-item tool screening primary care patients for lifestyle risk factors and mental health problems (smoking, alcohol and drug misuse, problem gambling, depression, anxiety, abuse, anger). Data analysis used descriptive statistics and non-parametric binomial tests with adjusting for clustering by practitioner using STATA survey analysis. Results Approximately 3/100 (3%) answered yes to the gambling question. Those worried about gambling more likely to be male OR 1.85 (95% CI 1.1 to 3.1). Increasing age reduced likelihood of gambling concerns – logistic regression for complex survey data OR = 0.99 (CI 95% 0.97 to 0.99) p = 0.04 for each year older. Patients concerned about gambling were significantly more likely (all p < 0.0001) to have concerns about their smoking, use of recreational drugs, and alcohol. Similarly there were more likely to indicate problems with depression, anxiety and anger control. No significant relationship with gambling worries was found for abuse, physical inactivity or weight concerns. Patients expressing concerns about gambling were significantly more likely to want help with smoking, other drug use, depression and anxiety. Conclusion Our questionnaire identifies patients who express a need for help with gambling and other lifestyle and mental health issues. Screening for gambling in primary care has the potential to identify individuals with multiple co-occurring disorders. PMID:16606465

Development and evaluation of a magnetic immunochromatographic test to detect Taenia solium, which causes taeniasis and neurocysticercosis in humans.

PubMed

Handali, Sukwan; Klarman, Molly; Gaspard, Amanda N; Dong, X Fan; Laborde, Ronald; Noh, John; Lee, Yeuk-Mui; Rodriguez, Silvia; Gonzalez, Armando E; Garcia, Hector H; Gilman, Robert H; Tsang, Victor C W; Wilkins, Patricia P

2010-04-01

Taeniasis/cysticercosis caused by Taenia solium is a frequent parasitic infection of the human brain in most of the world. Rapid and simple screening tools to identify taeniasis and cysticercosis cases are needed for control programs, mostly to identify tapeworm carriers which are the source of infection and need to be treated, or as tools for point-of-care case detection or confirmation. These screening assays should be affordable, reliable, rapid, and easy to perform. Immunochromatographic tests meet these criteria. To demonstrate proof of principle, we developed and evaluated two magnetic immunochromatographic tests (MICTs) for detection of human Taenia solium taeniasis antibodies (ES33-MICT) and neurocysticercosis antibodies (T24-MICT). These assays detected stage-specific antibodies by using two recombinant proteins, rES33 for detection of taeniasis antibodies and rT24H for detection of cysticercosis antibodies. The sensitivity and specificity of the ES33-MICT to detect taeniasis infections were 94.5% and 96%, respectively, and those of the T24-MICT to detect cases of human cysticercosis with two or more viable brain cysts were 93.9% and 98.9%, respectively. These data provide proof of principle that the ES33- and T24-MICTs provide rapid and suitable methods to identify individuals with taeniasis and cysticercosis.

An "EAR" on environmental surveillance and monitoring: A ...

EPA Pesticide Factsheets

Current environmental monitoring approaches focus primarily on chemical occurrence. However, based on chemical concentration alone, it can be difficult to identify which compounds may be of toxicological concern for prioritization for further monitoring or management. This can be problematic because toxicological characterization is lacking for many emerging contaminants. New sources of high throughput screening data like the ToxCast™ database, which contains data for over 9,000 compounds screened through up to 1,100 assays, are now available. Integrated analysis of chemical occurrence data with HTS data offers new opportunities to prioritize chemicals, sites, or biological effects for further investigation based on concentrations detected in the environment linked to relative potencies in pathway-based bioassays. As a case study, chemical occurrence data from a 2012 study in the Great Lakes Basin along with the ToxCast™ effects database were used to calculate exposure-activity ratios (EARs) as a prioritization tool. Technical considerations of data processing and use of the ToxCast™ database are presented and discussed. EAR prioritization identified multiple sites, biological pathways, and chemicals that warrant further investigation. Biological pathways were then linked to adverse outcome pathways to identify potential adverse outcomes and biomarkers for use in subsequent monitoring efforts. Anthropogenic contaminants are frequently reported in environm

A Quality Improvement Project: Using the STOP-BANG Tool in a Military Population to Improve Equity in Preoperative Screening.

PubMed

Dixon, Samuel E; Haas, Shelia A; Klopp, Audrey; Carlson, Judy

2016-10-01

The lack of a preoperative screening tool to detect obstructive sleep apnea (OSA) may lead to an increase in postoperative complications. The aim of the study was to implement a prescreening tool to identify diagnosed or undiagnosed OSA before a surgical procedure. The study was conducted in the surgical admission center and postanesthesia care unit at a military treatment facility in Hawaii. Participants of the study included military personnel, military family members, veterans, and veteran beneficiaries. The STOP-BANG (snore/tired/obstruction/pressure-body mass index/age/neck/gender) tool was used between April and June 2013 to identify and stratify 1,625 patients into low-risk, intermediate-risk, high-risk, and known OSA categories. The STOP-BANG tool confirmed the diagnosed OSA rate to be 13.48%, and increased at-risk OSA detection by 24.69%. Hawaiians/Pacific Islanders were more frequently found to be at risk with known OSA, likely to have complications, and be transferred to PACU 23-hour extended stay compared to other races and intermediate-risk and high-risk categories. The STOP-BANG tool identified and stratified surgical patients at risk for OSA and standardized OSA assessments. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Universal screening for alcohol misuse in acute medical admissions is feasible and identifies patients at high risk of liver disease.

PubMed

Westwood, Greta; Meredith, Paul; Atkins, Susan; Greengross, Peter; Schmidt, Paul E; Aspinall, Richard J

2017-09-01

Many people who die from alcohol related liver disease (ARLD) have a history of recurrent admissions to hospital, representing potential missed opportunities for intervention. Universal screening for alcohol misuse has been advocated but it is not known if this is achievable or effective at detecting individuals at high risk of ARLD. We systematically screened all admissions to the Acute Medical Unit (AMU) of a large acute hospital using an electronic data capture system in real time. Patients at an increasing risk of alcohol harm were referred for either brief intervention (BI) or further assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were recorded on admission diagnoses, alcohol unit consumption, previous attendances, previous admissions, length of stay and mortality. Between July 2011 and March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening. Of these, 1,122 (2.3%) were classified as "increasing", and 1,921 (4.0%) as "high" risk of alcohol harm. High risk patients had more hospital admissions in the three previous years (average 4.74) than the low (3.00) and increasing (2.92) risk groups (p<0.001). The high risk patients also had more frequent emergency department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81) groups (p<0.001 for both). A total of 1,396 (72.6%) of the high risk group were seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40. Compared to the other groups, high risk patients had a distinct profile of admissions with the most common diagnoses being mental health disorders, gastro-intestinal bleeding, poisoning and liver disease. Universal screening of admissions for alcohol misuse is feasible and identifies a cohort with frequent ED attendances, recurrent admissions and an elevated risk of ARLD. An additional group of patients at an increasing risk of alcohol harm can be identified in a range of common presentations. These patients can be targeted with interventions to reduce the burden of alcohol related harm. Lay summary: Many people who die from alcohol related liver disease (ARLD) have a recent history of recurrent admissions to hospital. These admissions may represent missed opportunities to intervene earlier and offer effective therapies for alcohol misuse. Unfortunately, we know that patients are often missed because medical staff may not routinely ask about alcohol consumption. In our study of over 50,000 admissions, we have demonstrated the feasibility of offering screening for alcohol misuse to all medical admissions to hospital and delivered this 24hours a day, 7days a week, with automatic referral to treatment services. We have shown that it is possible to identify those people who are at the highest risk of dependency, those who have attended the emergency department the most and those who are at an increased risk of ARLD. We hope this study will lead to improved detection and management of alcohol problems in acute hospitals. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Delivering colonoscopy screening for low-income populations in Suffolk County: strategies, outcomes, and benchmarks.

PubMed

Lane, Dorothy S; Messina, Catherine R; Cavanagh, Mary F; Anderson, Joseph C

2013-08-01

Current and pending legislation provides colorectal cancer screening reimbursement for previously uninsured populations. Colonoscopy is currently the screening method most frequently recommended by physicians for insured patients. The experience of the SCOPE (Suffolk County Preventive Endoscopy) demonstration project (Project SCOPE) at Stony Brook University Medical Center provides a model for delivering colonoscopy screening to low-income populations to meet anticipated increasing demands. Project SCOPE, based in the Department of Preventive Medicine, featured internal collaboration with the academic medical center's large gastroenterology practice and external collaboration with the Suffolk County Department of Health Services' network of community health centers. Colonoscopies were performed by faculty gastroenterologists or supervised fellows. Measures of colonoscopy performance were compared with quality indicators and differences between faculty and supervised fellows were identified. During a 40-month screening period, 800 initial colonoscopies were performed. Approximately 21% of women screened were found to have adenomatous polyps compared with 36% of men. Five cancers were detected. The majority of the population screened (70%) were members of minority populations. African American individuals had a higher percentage of proximally located adenomas (78%) compared with white individuals (65%) and Hispanics (49%), based on the location of the most advanced lesion. Hispanic individuals had a 36% lower risk of adenomas compared with white individuals. Performance measures including the percentage of procedures with adequate bowel preparation, cecum reached, scope withdrawal time, and adenoma detection rate met quality benchmarks when performed by either faculty or supervised fellows. Project SCOPE's operational strategies demonstrated a feasible method for an academic medical center to provide high-quality screening colonoscopy for low-income populations. © 2013 American Cancer Society.

Cardiopulmonary events during primary colonoscopy screening in an average risk population.

PubMed

Khalid-de Bakker, C A; Jonkers, D M; Hameeteman, W; de Ridder, R J; Masclee, A A; Stockbrügger, R W

2011-04-01

Large colorectal cancer screening studies using primary colonoscopy have reported a low risk of major complications. Studies on diagnostic and therapeutic colonoscopy have pointed to a frequent occurrence of(minor) cardiopulmonary events, and with the steady increase of colonoscopy screening, it is important to investigate their occurrence in colonoscopy screening. This study describes the frequency of bradycardia(pulse rate <60 min-1), hypotension (systolic blood pressure(SB P) <90 mmHg), hypoxaemia (blood oxygenation, SaO2<90%) and ECG changes during colonoscopy screening in an average-risk population (hospital personnel, n=214,mean age 54.0±3.8, 39.3% male), without significant comorbidity) and aims at identifying subject-related and/or endoscopic factors associated with their occurrence. All data were collected prospectively. During 214 consecutive primary screening colonoscopies under conscious sedation(midazolam and pethidine), on top of pulse rate and SaO2,blood pressure and a three-channel ECG were recorded every five minutes. No major complications or relevant ECG changes occurred. Hypoxaemia occurred in 119 (55.6%),hypotension in 19 (8.9%) and bradycardia in 12 subjects(5.6%). In multivariate analysis, the sedation level 3 increased the risk of hypoxaemia (OR 4.8, CI 1.7-13.7), and incomplete colonoscopy (OR 5.3, CI 1.6-18.1) was associated with hypotension. Subjects with bradycardia had a longer mean procedure time (38±12 vs. 29±12 min, p<0.05), which did not turn out as a risk factor in a multivariate analysis. Mainly procedure-related and not subject-related factors were found to be associated with the occurrence of cardiopulmonary events in primary colonoscopy screening in this relatively healthy screening population.

Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.

PubMed

Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G; Lillquist, Yolanda P; Waters, Paula J; Olpin, S; Andresen, B S; Palaty, Jan; Nelson, Judie; Vallance, Hilary

2008-01-01

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). Medium chain length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further. Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second mutation. Two novel mutations were identified (c.260T > C and c.382T > A). The estimated incidence of MCAD was approximately 1:12,000 live births. Upon frequent feeding and carnitine supplementation, none of the patients had metabolic crises or adverse outcomes. Frequency of MCAD in BC is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD.

Using Microarrays to Facilitate Positional Cloning: Identification of Tomosyn as an Inhibitor of Neurosecretion

PubMed Central

Dybbs, Michael; Ngai, John; Kaplan, Joshua M

2005-01-01

Forward genetic screens have been used as a powerful strategy to dissect complex biological pathways in many model systems. A significant limitation of this approach has been the time-consuming and costly process of positional cloning and molecular characterization of the mutations isolated in these screens. Here, the authors describe a strategy using microarray hybridizations to facilitate positional cloning. This method relies on the fact that premature stop codons (i.e., nonsense mutations) constitute a frequent class of mutations isolated in screens and that nonsense mutant messenger RNAs are efficiently degraded by the conserved nonsense-mediated decay pathway. They validate this strategy by identifying two previously uncharacterized mutations: (1) tom-1, a mutation found in a forward genetic screen for enhanced acetylcholine secretion in Caenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1 transcription factor gene. They further demonstrate the broad applicability of this strategy using other known mutants in C. elegans, Arabidopsis, and mouse. Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter secretion. These results also suggest that microarray hybridizations have the potential to significantly reduce the time and effort required for positional cloning. PMID:16103915

Drug-induced Brugada syndrome: Clinical characteristics and risk factors.

PubMed

Konigstein, Maayan; Rosso, Raphael; Topaz, Guy; Postema, Pieter G; Friedensohn, Limor; Heller, Karin; Zeltser, David; Belhassen, Bernard; Adler, Arnon; Viskin, Sami

2016-05-01

Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome. Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed to define characteristics that identify patients prone to developing this complication. For each patient with drug-induced Brugada syndrome who had an ECG recorded in the absence of drugs, we included 5 healthy controls matched by gender and age. All ECGs were evaluated for Brugada-like abnormalities. Seventy-four cases of drug-induced Brugada syndrome from noncardiac medications were identified: 77% were male, and drug toxicity was involved in 46%. Drug-induced Brugada syndrome from oral medications generally occurred weeks after the initiation of therapy. Mortality was 13%. By definition, all cases had a type I Brugada pattern during drug therapy. Nevertheless, their ECG in the absence of drugs was more frequently abnormal than the ECG of controls (56% vs 33%, P = .04). Drug-induced Brugada syndrome from noncardiac drugs occurs predominantly in adult males, is frequently due to drug toxicity, and occurs late after the onset of therapy. Minor changes are frequently noticeable on baseline ECG, but screening is impractical because of a prohibitive false-positive rate. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

[Would the Screening of Common Mental Disorders in Primary-Care Health Services Hyper-Frequent Patients Be Useful?].

PubMed

Rincón-Hoyos, Hernán G; López, Mérida R Rodríguez; Ruiz, Ana María Villa; Hernández, Carlos Augusto; Ramos, Martha Lucía

2012-12-01

Hyper-frequentation in health services is a problem for patients, their families and the institutions. This study is aimed at determining the frequency and characteristics of common mental disorders in hyper-frequent patients showing vague symptoms and signs at a primary healthcare service during the year 2007 in the city of Cali (Colombia). Cross sectional. The most frequent mental disorders in hyper-frequent patients were detected through a telephone interview which included several modules of the PRIME MD instrument. In general, healthcare service hyper-frequenters are working women, 38,7-year old in average. Basically, the consultation is due to cephalalgia but they also exhibit a high prevalence of common mental disorders (somatization, depression and anxiety) not easily diagnosed by physicians in primary care. Expenses for additional health activities generated by these patients are attributed basically to medical consultation and required procedures. Considering hyper-frequenters in health care services as a risk group in terms of common mental disorders involves screening as an efficient strategy to prevent abuse in service use and to improve satisfaction with the attention received. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Current status of nutritional support for hospitalized children: a nationwide hospital-based survey in South Korea.

PubMed

Kim, Seung; Lee, Eun Hye; Yang, Hye Ran

2018-06-01

The prevalence of malnutrition among hospitalized children ranges between 12% and 24%. Although the consequences of hospital malnutrition are enormous, it is often unrecognized and untreated. The aim of this study was to identify the current status of in-hospital nutrition support for children in South Korea by carrying out a nationwide hospital-based survey. Out of 345 general and tertiary hospitals in South Korea, a total of 53 institutes with pediatric gastroenterologists and more than 10 pediatric inpatients were selected. A questionnaire was developed by the nutrition committee of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition. The questionnaires were sent to pediatric gastroenterologists in each hospital. Survey was performed by e-mails. Forty hospitals (75.5%) responded to the survey; 23 of them were tertiary hospitals, and 17 of them were general hospitals. Only 21 hospitals (52.5%) had all the required nutritional support personnel (including pediatrician, nutritionist, pharmacist, and nurse) assigned to pediatric patients. Routine nutritional screening was performed in 22 (55.0%) hospitals on admission, which was lower than that in adult patients (65.8%). Nutritional screening tools varied among hospitals; 33 of 40 (82.5%) hospitals used their own screening tools. The most frequently used nutritional assessment parameters were weight, height, hemoglobin, and serum albumin levels. In our nationwide hospital-based survey, the most frequently reported main barriers of nutritional support in hospitals were lack of manpower and excessive workload, followed by insufficient knowledge and experience. Although this nationwide hospital-based survey targeted general and tertiary hospitals with pediatric gastroenterologists, manpower and medical resources for nutritional support were still insufficient for hospitalized children, and nutritional screening was not routinely performed in many hospitals. More attention to hospital malnutrition and additional national policies for nutritional support in hospitals are required to ensure appropriate nutritional management of hospitalized pediatric patients.

EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

PubMed

Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

2016-04-01

Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC.

A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

PubMed

Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

2017-01-19

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Screen Display Syntax for CAI.

ERIC Educational Resources Information Center

Richards, Boyd F.; Salisbury, David F.

1987-01-01

Describes four storyboard techniques frequently used in designing computer assisted instruction (CAI) programs, and explains screen display syntax (SDS), a new technique combining the major advantages of the storyboard techniques. SDS was developed to facilitate communication among designers, programmers, and editors working on a large CAI basic…

Age, Body Mass Index, and Frequency of Sexual Activity are Independent Predictors of Testosterone Deficiency in Men With Erectile Dysfunction.

PubMed

Pagano, Matthew J; De Fazio, Adam; Levy, Alison; RoyChoudhury, Arindam; Stahl, Peter J

2016-04-01

To identify clinical predictors of testosterone deficiency (TD) in men with erectile dysfunction (ED), thereby identifying subgroups that are most likely to benefit from targeted testosterone screening. Retrospective review was conducted on 498 men evaluated for ED between January 2013 and July 2014. Testing for TD by early morning serum measurement was offered to all eligible men. Patients with history of prostate cancer or testosterone replacement were excluded. Univariable linear regression was conducted to analyze 19 clinical variables for associations with serum total testosterone (TT), calculated free testosterone (cFT), and TD (T <300 ng/dL or cFT <6.5 ng/dL). Variables significant on univariable analysis were included in multiple regression models. A total of 225 men met inclusion criteria. Lower TT levels were associated with greater body mass index (BMI), less frequent sexual activity, and absence of clinical depression on multiple regression analysis. TT decreased by 49.5 ng/dL for each 5-point increase in BMI. BMI and age were the only independent predictors of cFT levels on multivariable analysis. Overall, 62 subjects (27.6%) met criteria for TD. Older age, greater BMI, and less frequent sexual activity were the only independent predictors of TD on multiple regression. We observed a 2.2-fold increase in the odds of TD for every 5-point increase in BMI, and a 1.8-fold increase for every 10 year increase in age. Men with ED and elevated BMI, advanced age, or infrequent sexual activity appear to be at high risk of TD, and such patients represent excellent potential candidates for targeted testosterone screening. Copyright © 2016 Elsevier Inc. All rights reserved.

ARX polyalanine expansions are highly implicated in familial cases of mental retardation with infantile epilepsy and/or hand dystonia.

PubMed

Cossée, Mireille; Faivre, Laurence; Philippe, Christophe; Hichri, Heifa; de Saint-Martin, Anne; Laugel, Vincent; Bahi-Buisson, Nadia; Lemaitre, Jean-François; Leheup, Bruno; Delobel, Bruno; Demeer, Bénédicte; Poirier, Karine; Biancalana, Valérie; Pinoit, Jean-Michel; Julia, Sophie; Chelly, Jamel; Devys, Didier; Mandel, Jean-Louis

2011-01-01

Mutations in the ARX gene cause both nonsyndromic and several forms of syndromic mental retardation (MR). Two polyalanine (polyA) expansions of ARX are recurrent mutations. The most common one, the c.428_451dup, is associated with a wide spectrum of phenotypes, ranging from the most severe West syndrome to Partington syndrome (MR and hand dystonia), and even nonsyndromic X-linked mental retardation (NS-XLMR). Studies of patients not selected for specific clinical signs showed that the c.428_451dup is relatively frequent in families harboring X-linked MR (7.5%), but less common in familial cases compatible with X-linked NR (1%), and very rare in sporadic cases (0.1%). The c.333_334ins(GCG)7 expansion is less frequent and mainly associated with West syndrome. We screened for both ARX polyA expansions in 98 unrelated patients selected for the presence of NR associated with different types of epilepsy and/or with hand dystonia. We also studied two families with an initial diagnosis of NS-XLMR, one of which was identified as showing linkage to the ARX locus. The c.428_451dup was identified in three patients and the c.333_334ins(GCG)7 in one; all of the patients were from families with two affected brothers. We also found the c.428_451dup in the family linked to ARX, and clinical re-evaluation showed subtle, previously undetected signs. Our study illustrates that ARX polyA expansions are primarily associated with syndromic MR and shows a higher yield (18% in our cohort) when these mutations are screened in familial cases of MR with epilepsy and/or dystonia. Copyright © 2010 Wiley-Liss, Inc.

Stray animal and human defecation as sources of soil-transmitted helminth eggs in playgrounds of Peninsular Malaysia.

PubMed

Mohd Zain, S N; Rahman, R; Lewis, J W

2015-11-01

Soil contaminated with helminth eggs and protozoan cysts is a potential source of infection and poses a threat to the public, especially to young children frequenting playgrounds. The present study determines the levels of infection of helminth eggs in soil samples from urban and suburban playgrounds in five states in Peninsular Malaysia and identifies one source of contamination via faecal screening from stray animals. Three hundred soil samples from 60 playgrounds in five states in Peninsular Malaysia were screened using the centrifugal flotation technique to identify and determine egg/cyst counts per gram (EPG) for each parasite. All playgrounds, especially those in Penang, were found to be contaminated with eggs from four nematode genera, with Toxocara eggs (95.7%) the highest, followed by Ascaris (93.3%), Ancylostoma (88.3%) and Trichuris (77.0%). In addition, faeces from animal shelters were found to contain both helminth eggs and protozoan cysts, with overall infection rates being 54% and 57% for feline and canine samples, respectively. The most frequently occurring parasite in feline samples was Toxocara cati (37%; EPG, 42.47 ± 156.08), while in dog faeces it was Ancylostoma sp. (54%; EPG, 197.16 ± 383.28). Infection levels also tended to be influenced by season, type of park/playground and the texture of soil/faeces. The occurrence of Toxocara, Ancylostoma and Trichuris eggs in soil samples highlights the risk of transmission to the human population, especially children, while the presence of Ascaris eggs suggests a human source of contamination and raises the issue of hygiene standards and public health risks at sites under investigation.

Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing

PubMed Central

Glaus, Esther; Lorenz, Birgit; Netzer, Christian; Li, Yün; Schambeck, Maria; Wittmer, Mariana; Feil, Silke; Kirschner-Schwabe, Renate; Rosenberg, Thomas; Cremers, Frans P.M.; Bergen, Arthur A.B.; Barthelmes, Daniel; Baraki, Husnia; Schmid, Fabian; Tanner, Gaby; Fleischhauer, Johannes; Orth, Ulrike; Becker, Christian; Wegscheider, Erika; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno Jörn; Gal, Andreas; Berger, Wolfgang

2008-01-01

Purpose The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. Methods In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. Results This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3’-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. Conclusions RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families. PMID:18552978

Screening the Budding Yeast Genome Reveals Unique Factors Affecting K2 Toxin Susceptibility

PubMed Central

Servienė, Elena; Lukša, Juliana; Orentaitė, Irma

2012-01-01

Background Understanding how biotoxins kill cells is of prime importance in biomedicine and the food industry. The budding yeast (S. cerevisiae) killers serve as a convenient model to study the activity of biotoxins consistently supplying with significant insights into the basic mechanisms of virus-host cell interactions and toxin entry into eukaryotic target cells. K1 and K2 toxins are active at the cell wall, leading to the disruption of the plasma membrane and subsequent cell death by ion leakage. K28 toxin is active in the cell nucleus, blocking DNA synthesis and cell cycle progression, thereby triggering apoptosis. Genome-wide screens in the budding yeast S. cerevisiae identified several hundred effectors of K1 and K28 toxins. Surprisingly, no such screen had been performed for K2 toxin, the most frequent killer toxin among industrial budding yeasts. Principal Findings We conducted several concurrent genome-wide screens in S. cerevisiae and identified 332 novel K2 toxin effectors. The effectors involved in K2 resistance and hypersensitivity largely map in distinct cellular pathways, including cell wall and plasma membrane structure/biogenesis and mitochondrial function for K2 resistance, and cell wall stress signaling and ion/pH homeostasis for K2 hypersensitivity. 70% of K2 effectors are different from those involved in K1 or K28 susceptibility. Significance Our work demonstrates that despite the fact that K1 and K2 toxins share some aspects of their killing strategies, they largely rely on different sets of effectors. Since the vast majority of the host factors identified here is exclusively active towards K2, we conclude that cells have acquired a specific K2 toxin effectors set. Our work thus indicates that K1 and K2 have elaborated different biological pathways and provides a first step towards the detailed characterization of K2 mode of action. PMID:23227207

Screening the budding yeast genome reveals unique factors affecting K2 toxin susceptibility.

PubMed

Servienė, Elena; Lukša, Juliana; Orentaitė, Irma; Lafontaine, Denis L J; Urbonavičius, Jaunius

2012-01-01

Understanding how biotoxins kill cells is of prime importance in biomedicine and the food industry. The budding yeast (S. cerevisiae) killers serve as a convenient model to study the activity of biotoxins consistently supplying with significant insights into the basic mechanisms of virus-host cell interactions and toxin entry into eukaryotic target cells. K1 and K2 toxins are active at the cell wall, leading to the disruption of the plasma membrane and subsequent cell death by ion leakage. K28 toxin is active in the cell nucleus, blocking DNA synthesis and cell cycle progression, thereby triggering apoptosis. Genome-wide screens in the budding yeast S. cerevisiae identified several hundred effectors of K1 and K28 toxins. Surprisingly, no such screen had been performed for K2 toxin, the most frequent killer toxin among industrial budding yeasts. We conducted several concurrent genome-wide screens in S. cerevisiae and identified 332 novel K2 toxin effectors. The effectors involved in K2 resistance and hypersensitivity largely map in distinct cellular pathways, including cell wall and plasma membrane structure/biogenesis and mitochondrial function for K2 resistance, and cell wall stress signaling and ion/pH homeostasis for K2 hypersensitivity. 70% of K2 effectors are different from those involved in K1 or K28 susceptibility. Our work demonstrates that despite the fact that K1 and K2 toxins share some aspects of their killing strategies, they largely rely on different sets of effectors. Since the vast majority of the host factors identified here is exclusively active towards K2, we conclude that cells have acquired a specific K2 toxin effectors set. Our work thus indicates that K1 and K2 have elaborated different biological pathways and provides a first step towards the detailed characterization of K2 mode of action.

Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.

PubMed

Tsukamoto, Yoshihiro; Ohtsu, Naoki; Echizenya, Smile; Otsuguro, Satoko; Ogura, Ryosuke; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Ichikawa, Satoshi; Sakaitani, Masahiro; Matsuda, Akira; Maenaka, Katsumi; Fujii, Yukihiko; Kondo, Toru

2016-08-01

Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025. © 2016 AlphaMed Press.

Nutritional status and nutrition risk screening in hospitalized children in New Zealand.

PubMed

Moeeni, Vesal; Walls, Tony; Day, Andrew S

2013-09-01

Children requiring hospitalization are at risk of malnutrition. This study aimed to define the nutritional status of paediatric inpatients in comparison with healthy children and to compare and contrast the feasibility and validity of three nutritional risk screening (NRS) tools in the hospitalized children. A total of 162 children admitted to Christchurch Hospital were assessed along with a similar group of healthy children. Their nutritional state was assessed and classified using standard criteria. The NRS tools were applied, and patients were classified into low-, medium- and high-risk groups. The feasibility and validity of the tools were assessed. Under-nutrition was more frequent in the inpatient group (9.9% vs. 3.7%; p = 0.04), whereas both groups had similar rates of overweight/obesity. NRS tools were able to identify between 81% and 100% of the malnourished patients in the medium- to high-risk groups. Undernourished patients had longer hospital stay than well-nourished patients. Hospitalized children have higher rates of under-nutrition than healthy children in NZ. The three NRS tools were able to identify children at nutritional risk with differing utility. In this setting, STRONGkids was the most reliable tool. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Low prevalence of Chlamydia trachomatis infection in asymptomatic young Swiss men.

PubMed

Baud, David; Jaton, Katia; Bertelli, Claire; Kulling, Jean-Pierre; Greub, Gilbert

2008-04-12

Prevalence and risk factors for Chlamydia trachomatis infection among young men in Switzerland is still unknown. The objective of the present study was to assess prevalence and risk factors for C. trachomatis infection in young Swiss men. 517 young Swiss men were enrolled in this cross-sectional study during their compulsory military recruitment. Participants completed a questionnaire and gave urine samples which were screened for C. trachomatis DNA by PCR. Genotyping of positive samples was done by amplification and sequencing the ompA gene. The prevalence of chlamydial infection among young Swiss male was 1.2% (95% confidence interval [95%CI], 0.4-2.5%). C. trachomatis infection was only identified among the 306 men having multiple sexual partner. Although frequent, neither unprotected sex (absence of condom use), nor alcohol and drug abuse were associated with chlamydial infection. Men living in cities were more frequently infected (2.9%, 95%CI 0.8-7.4%) than men living in rural areas (0.5%, 95%CI 0.1-1.9%, p = 0.046). Moreover, naturalised Swiss citizens were more often positive (4.9%, 95%CI 1.3-12.5%) than native-born Swiss men (0.5%, 95%CI 0.1-1.7%, p = 0.003). In comparison with other countries, the prevalence of chlamydial infection in men is extremely low in Switzerland, despite a significant prevalence of risky sexual behaviour. C. trachomatis infection was especially prevalent in men with multiple sexual partners. Further research is required (i) to define which subgroup of the general population should be routinely screened, and (ii) to test whether such a targeted screening strategy will be effective to reduce the prevalence of chlamydial infection among this population.

Understanding the Low Level of Cervical Cancer Screening in Masaka Uganda Using the ASE Model: A Community-Based Survey.

PubMed

Twinomujuni, Cyprian; Nuwaha, Fred; Babirye, Juliet Ndimwibo

2015-01-01

Cervical cancer is one of the leading causes of cancer deaths among women globally and its impact is mostly felt in developing countries like Uganda where its prevalence is higher and utilization of cancer screening services is low. This study aimed to identify factors associated with intention to screen for cervical cancer among women of reproductive age in Masaka Uganda using the attitude, social influence and self efficacy (ASE) model. A descriptive community based survey was conducted among 416 women. A semi-structured interviewer administered questionnaire was used to collect data. Unadjusted and adjusted prevalence ratios (PR) were computed using a generalized linear model with Poisson family and a log link using STATA 12. Only 7% (29/416) of our study respondents had ever screened for cervical cancer although a higher proportion (63%, 262/416) reported intention to screen for cervical cancer. The intention to screen for cervical cancer was higher among those who said they were at risk of developing cervical cancer (Adjusted prevalence ratio [PR] 2.0, 95% CI 1.60-2.58), those who said they would refer other women for screening (Adjusted PR 1.4, 95% CI 1.06-1.88) and higher among those who were unafraid of being diagnosed with cervical cancer (Adjusted PR 1.6, 95% CI 1.36-1.93). Those who reported discussions on cervical cancer with health care providers (Adjusted PR 1.2, 95% CI 1.05-1.44), those living with a sexual partner (Adjusted PR 1.4, 95% CI 1.11-1.68), and those who were formally employed (Adjusted PR 1.2, 95% CI 1.03-1.35) more frequently reported intention to screen for cervical cancer. In conclusion, health education to increase risk perception, improve women's attitudes towards screening for cervical cancer and address the fears held by the women would increase intention to screen for cervical cancer. Interventions should also target increased discussions with health workers.

ARID1B is a specific vulnerability in ARID1A-mutant cancers

PubMed Central

Helming, Katherine C.; Wang, Xiaofeng; Wilson, Boris G.; Vazquez, Francisca; Haswell, Jeffrey R.; Manchester, Haley E.; Kim, Youngha; Kryukov, Gregory V.; Ghandi, Mahmoud; Aguirre, Andrew J.; Jagani, Zainab; Wang, Zhong; Garraway, Levi A.; Hahn, William C.; Roberts, Charles W. M.

2014-01-01

Summary Recent studies have revealed that ARID1A is frequently mutated across a wide variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, a related but mutually exclusive homolog of ARID1A in the SWI/SNF chromatin remodeling complex, as the number one gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation. Intriguingly, we also find that ARID1A and ARID1B are frequently co-mutated in cancer, but that ARID1A-deficient cancers retain at least one ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers. PMID:24562383

High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis.

PubMed

Nettore, I C; Desiderio, S; De Nisco, E; Cacace, V; Albano, L; Improda, N; Ungaro, P; Salerno, M; Colao, A; Macchia, P E

2018-06-01

Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined "thyroid dysgenesis" (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2.1 and PAX8 and it has been associated to the hypothyroid phenotype in mice carrying a single Nkx2.1 and Pax8 genes (double heterozygous knock-out). The work evaluates the possible involvement of DNAJC17 in the pathogenesis of TD. High-resolution DNA melting analysis (HRM) and direct sequencing have been used to screen for mutations in the DNAJC17 coding sequence in 89 patients with TD. Two mutations have been identified in the coding sequence of DNAJC17 gene, one in exon 5 (c.350A>C; rs79709714) and one in exon 9 (c.610G>C; rs117485355). The last one is a rare variant, while the rs79709714 is a polymorphism. Both are present in databases and the frequency of the alleles is not different between TD patients and controls. DNAJC17 mutations are not frequently present in patients with TD.

Contact allergy to common ingredients in hair dyes.

PubMed

Søsted, Heidi; Rustemeyer, Thomas; Gonçalo, Margarida; Bruze, Magnus; Goossens, An; Giménez-Arnau, Ana M; Le Coz, Christophe J; White, Ian R; Diepgen, Thomas L; Andersen, Klaus E; Agner, Tove; Maibach, Howard; Menné, Torkil; Johansen, Jeanne D

2013-07-01

p-Phenylenediamine (PPD) is the primary patch test screening agent for hair dye contact allergy, and approximately 100 different hair dye chemicals are allowed. To examine whether PPD is an optimal screening agent for diagnosing hair dye allergy or whether other clinically important sensitizers exist. Two thousand nine hundred and thirty-nine consecutive patients in 12 dermatology clinics were patch tested with five hair dyes available from patch test suppliers. Furthermore, 22 frequently used hair dye ingredients not available from patch test suppliers were tested in subgroups of ~500 patients each. A positive reaction to PPD was found in 4.5% of patients, and 2.8% reacted to toluene-2,5-diamine (PTD), 1.8% to p-aminophenol, 1% to m-aminophenol, and 0.1% to resorcinol; all together, 5.3% (n = 156). Dying hair was the most frequently reported cause of the allergy (55.4%); so-called 'temporary henna' tattoos were the cause in 8.5% of the cases. p-Methylaminophenol gave a reaction in 20 patients (2.2%), 3 of them with clinical relevance, and no co-reaction with the above five well-known hair dyes. Hair dyes are the prime cause of PPD allergy. PPD identifies the majority of positive reactions to PTD, p-aminophenol and m-aminophenol, but not all, which justifies additional testing with hair dye ingredients from the used product. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The occurrence of high-risk factors for hearing loss in very-low-birth-weight neonates: a retrospective exploratory study of targeted hearing screening.

PubMed

Kanji, Amisha; Khoza-Shangase, Katijah

2012-12-01

The current study aimed at determining the type and frequency of high-risk factors for hearing loss in a group of very-low-birth-weight (VLBW) neonates in a tertiary hospital in South Africa with the objective of collating evidence that could be used in arguing for or against revisiting targeted hearing screening in developing countries. Furthermore, the study aimed at investigating the relationship between the identified high-risk factors and hearing screening results. In a retrospective data review design, data were collated from files from the VLBW project; this included hearing screening records, as well as records from participant medical and audiology files. Records of 86 neonates with birth weights ranging between 680 g and 1500 g were reviewed. Findings indicated that neonatal jaundice, exposure to human immunodeficiency virus (HIV), mechanical or assisted ventilation, and neonatal intensive care unit stay greater than 48 hours were the most frequently occurring high-risk factors for hearing loss in the current sample. These factors are consistent with those listed in the high-risk register of the Health Professions Council of South Africa for the South African context. Findings confirm the complexity of risk factors, and the influence that a variety of factors such as poor follow-up or return rate might have on the implementation of early hearing detection and intervention. The importance of establishing context-specific risk factors for effective implementation of targeted screening protocols where niversal newborn hearing screening is not yet a reality was highlighted by the current study.

The development of an observational screening tool to assess safe, effective and appropriate walking aid use in people with multiple sclerosis.

PubMed

Eitzen, Abby; Finlayson, Marcia; Carolan-Laing, Leanne; Nacionales, Arthur Junn; Walker, Christie; O'Connor, Josephine; Asano, Miho; Coote, Susan

2017-08-01

The purpose of this study was to identify potential items for an observational screening tool to assess safe, effective and appropriate walking aid use among people with multiple sclerosis (MS). Such a tool is needed because of the association between fall risk and mobility aid use in this population. Four individuals with MS were videotaped using a one or two straight canes, crutches or a rollator in different settings. Seventeen health care professionals from Canada, Ireland and the United States were recruited, and viewed the videos, and were then interviewed about the use of the devices by the individuals in the videos. Interview questions addressed safety, effectiveness and appropriateness of the device in the setting. Data were analyzed qualitatively. Coding consistency across raters was evaluated and confirmed. Nineteen codes were identified as possible items for the screening tool. The most frequent issues raised regardless of setting and device were "device used for duration/abandoned", "appropriate device", "balance and stability", "device technique", "environmental modification" and "hands free." With the identification of a number of potential tool items, researchers can now move forward with the development of the tool. This will involve consultation with both healthcare professionals and people with MS. Implications for rehabilitation Falls among people with multiple sclerosis are associated with mobility device use and use of multiple devices is associated with greater falls risk. The ability to assess for safe, effective and efficient use of walking aids is therefore important, no tools currently exist for this purpose. The codes arising from this study will be used to develop a screening tool for safe, effective and efficient walking aid use with the aim of reducing falls risk.

Clinical experience of laboratory follow-up with noninvasive prenatal testing using cell-free DNA and positive microdeletion results in 349 cases.

PubMed

Schwartz, S; Kohan, M; Pasion, R; Papenhausen, P R; Platt, L D

2018-02-01

Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell-free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow-up of positive NIPT screens for microdeletions. Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated. The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result. Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis. © 2018 John Wiley & Sons, Ltd.

Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells.

PubMed

Jaiswal, Alok; Peddinti, Gopal; Akimov, Yevhen; Wennerberg, Krister; Kuznetsov, Sergey; Tang, Jing; Aittokallio, Tero

2017-06-01

Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity. We performed a systematic, quantitative analysis of the consistency between two genome-wide shRNA screens conducted on a compendium of cancer cell lines, and also compared several gene summarization methods for inferring gene essentiality from shRNA level data. We then devised novel concepts of seed essentiality and shRNA family, based on seed region sequences of shRNAs, to study in-depth the contribution of seed-mediated off-target effects to the consistency of the two screens. We further investigated two seed-sequence properties, seed pairing stability, and target abundance in terms of their capability to minimize the off-target effects in post-screening data analysis. Finally, we applied this novel methodology to identify genetic interactions and synthetic lethal partners of cancer drivers, and confirmed differential essentiality phenotypes by detailed CRISPR/Cas9 experiments. Using the novel concepts of seed essentiality and shRNA family, we demonstrate how genome-wide loss-of-function profiling of a common set of cancer cell lines can be actually made fairly reproducible when considering seed-mediated off-target effects. Importantly, by excluding shRNAs having higher propensity for off-target effects, based on their seed-sequence properties, one can remove noise from the genome-wide shRNA datasets. As a translational application case, we demonstrate enhanced reproducibility of genetic interaction partners of common cancer drivers, as well as identify novel synthetic lethal partners of a major oncogenic driver, PIK3CA, supported by a complementary CRISPR/Cas9 experiment. We provide practical guidelines for improved design and analysis of genome-wide loss-of-function profiling and demonstrate how this novel strategy can be applied towards improved mapping of genetic dependencies of cancer cells to aid development of targeted anticancer treatments.

Insufficient sleep among elementary and middle school students is linked with elevated soda consumption and other unhealthy dietary behaviors.

PubMed

Franckle, Rebecca L; Falbe, Jennifer; Gortmaker, Steven; Ganter, Claudia; Taveras, Elsie M; Land, Thomas; Davison, Kirsten K

2015-05-01

This study examines the extent to which insufficient sleep is associated with diet quality in students taking part in the Massachusetts Childhood Obesity Research Demonstration Project. Data were collected in Fall 2012 for all 4th and 7th grade children enrolled in public schools in two Massachusetts communities. During annual body mass index (BMI) screening, students completed a survey that assessed diet, physical activity, screen time, and sleep. Of the 2456 enrolled students, 1870 (76%) had complete survey data. Generalized estimating equations were used to examine associations between sleep duration and dietary outcomes (vegetables, fruits, 100% juice, juice drinks, soda, sugar-sweetened beverages and water), accounting for clustering by school. Models were adjusted for community, grade, race/ethnicity, gender, television in the bedroom, screen time, and physical activity. In adjusted models, students who reported sleeping < 10 hours/day consumed soda more frequently (β = 0.11, 95% CI: 0.03, 0.20) and vegetables less frequently (β = -0.09, 95% CI: -0.18, -0.01) compared with students who reported ≥ 10 hours/day. No significant associations were observed between sleep duration and fruits, 100% juice, juice drinks or water. In this population, insufficient sleep duration was associated with more frequent soda and less frequent vegetable consumption. Longitudinal research is needed to further examine these relationships. Copyright © 2015. Published by Elsevier Inc.

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis.

PubMed

Ammann, Sandra; Lehmberg, Kai; Zur Stadt, Udo; Klemann, Christian; Bode, Sebastian F N; Speckmann, Carsten; Janka, Gritta; Wustrau, Katharina; Rakhmanov, Mirzokhid; Fuchs, Ilka; Hennies, Hans C; Ehl, Stephan

2017-11-01

We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years.

[Technology and prevention in the era of mobile health: applications for cancer screening programs].

PubMed

Bert, Fabrizio; Gualano, Maria Rosaria; Clemente, Salvatore; Villa, Giulia; Siliquini, Roberta

2017-01-01

The Italian national health system provides screening to detect breast, colorecatal and cervical cancers, however, population adherence is not as high as expected. Smartphones and their applications (apps) could be used as a tool to communicate with the population and to help improve adherence. The aim of this study was to analyze the features and functions of smartphone applications aimed at secondary prevention of oncological diseases. In February 2016, we reviewed online app stores, using specific key-words, to search for available apps for cancer screening. We identified 32 apps meeting our inclusion criteria. The most frequent types of app are breast cancer (13/32) and cervical cancer (4/32) screening apps. We also found apps addressing secondary prevention of cancers for which screening is not provided to the Italian population (melanoma, prostate cancer and hepatocellular carcinoma). The most common features are: information providers (22/32), risk calculators (10/32), reminders for appointments and tests (7/32). Only one app has been validated for diagnostic accuracy or utility using established international certification (CE Marking). The results show a large potential for development and utilization of applications in secondary prevention. Despite their potential usefulness, there are also disadvantages such as language barriers (only 2 of 32 apps are in Italian), and the digital divide. Future efforts should focus on improving education regarding approaches to technologies, strengthen national and international regulations and monitoring inequalities in access to services.

Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS

PubMed Central

Minden, Sarah L.; Feinstein, Anthony; Kalb, Rosalind C.; Miller, Deborah; Mohr, David C.; Patten, Scott B.; Bever, Christopher; Schiffer, Randolph B.; Gronseth, Gary S.; Narayanaswami, Pushpa

2014-01-01

Objective: To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). Methods: We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Results and recommendations: Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population. PMID:24376275

A genome-wide RNAi screen identifies novel targets of neratinib sensitivity leading to neratinib and paclitaxel combination drug treatments.

PubMed

Seyhan, Attila A; Varadarajan, Usha; Choe, Sung; Liu, Yan; McGraw, John; Woods, Matthew; Murray, Stuart; Eckert, Amy; Liu, Wei; Ryan, Terence E

2011-06-01

ErbB2 is frequently activated in tumors, and influences a wide array of cellular functions, including proliferation, apoptosis, cell motility and adhesion. HKI-272 (neratinib) is a small molecule pan-kinase inhibitor of the ErbB family of receptor tyrosine kinases, and shows strong antiproliferative activity in ErbB2-overexpressing breast cancer cells. We undertook a genome-wide pooled lentiviral RNAi screen to identify synthetic lethal or enhancer (synthetic modulator screen) genes that interact with neratinib in a human breast cancer cell line (SKBR-3). These genes upon knockdown would modulate cell viability in the presence of subeffective concentrations of neratinib. We discovered a diverse set of genes whose depletion selectively impaired or enhanced the viability of SKBR-3 cells in the presence of neratinib. We observed diverse pathways including EGFR, hypoxia, cAMP, and protein ubiquitination that, when co-treated with RNAi and neratinib, resulted in arrest of cell proliferation. Examining the changes of these genes and their protein products also led to a rationale for clinically relevant drug combination treatments. Treatment of cells with either paclitaxel or cytarabine in combination with neratinib resulted in a strong antiproliferative effect. The identification of novel mediators of cellular response to neratinib and the development of potential drug combination treatments have expanded our understanding of neratinib's mode-of-action for the development of more effective therapeutic regimens. Notably, our findings support a paclitaxel and neratinib phase III clinical trial in breast cancer patients.

Secondary arterial hypertension: when, who, and how to screen?

PubMed

Rimoldi, Stefano F; Scherrer, Urs; Messerli, Franz H

2014-05-14

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.

Client Attitudes toward Alcohol Use Self-Report

ERIC Educational Resources Information Center

Book, Sarah W.; Thomas, Suzanne E.; Stewart, Scott H.; Miller, Peter M.

2012-01-01

Because psychiatric illnesses and problematic alcohol use frequently co-occur and heavy alcohol use can exacerbate depression and anxiety, mental health clinicians should perform alcohol-use screenings. The aim of this study was to determine if psychiatric patients would be accepting of their mental health clinician screening them for heavy…

Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects.

PubMed

Pagniez-Mammeri, Hélène; Lombes, Anne; Brivet, Michèle; Ogier-de Baulny, Hélène; Landrieu, Pierre; Legrand, Alain; Slama, Abdelhamid

2009-04-01

Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone oxydoreductase deficiency is the most common cause of respiratory chain defects. Molecular bases of complex I deficiencies are rarely identified because of the dual genetic origin of this multi-enzymatic complex (nuclear DNA and mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a rapid method to screen patients with isolated complex I deficiencies for nuclear genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their coding sequences in 8 patients with a biochemically proved complex I deficiency. Single nucleotide polymorphisms and missense mutations were detected in 18.7% of the cDNA fragments by Surveyor nuclease treatment. Molecular defects were detected in 3 patients. Surveyor nuclease screening is a reliable method for genotyping nuclear complex I deficiencies, easy to interpret, and limits the number of sequence reactions. Its use will enhance the possibility of prenatal diagnosis and help us for a better understanding of complex I molecular defects.

Synergistic Interactions with PI3K Inhibition that Induce Apoptosis. | Office of Cancer Genomics

Cancer.gov

Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition.

How can clinicians detect and treat autism early? Methodological trends of technology use in research

PubMed Central

Bölte, S; Bartl-Pokorny, KD; Jonsson, U; Berggren, S; Zhang, D; Kostrzewa, E; Falck-Ytter, T; Einspieler, C; Pokorny, FB; Jones, EJH; Roeyers, H; Charman, T; Marschik, PB

2018-01-01

We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965-2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye-tracking were the most frequently used technologies. Conclusion The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention. PMID:26479859

A literature review of the application of the Geriatric Depression Scale, Depression Anxiety Stress Scales and Post-traumatic Stress Disorder Checklist to community nursing cohorts.

PubMed

Allen, Jacqui; Annells, Merilyn

2009-04-01

To explore through literature review the appropriateness of three common tools for use by community nurses to screen war veteran and war widow(er) clients for depression, anxiety and post-traumatic stress disorder. War veterans and, to a lesser extent, war widow(er)s, are prone to mental health challenges, especially depression, anxiety and post-traumatic stress disorder. Community nurses do not accurately identify such people with depression and related disorders although they are well positioned to do so. The use of valid and reliable self-report tools is one method of improving nurses' identification of people with actual or potential mental health difficulties for referral to a general practitioner or mental health practitioner for diagnostic assessment and treatment. The Geriatric Depression Scale, Depression Anxiety Stress Scales and Post-traumatic Stress Disorder Checklist are frequently recommended for mental health screening but the appropriateness of using the tools for screening war veteran and war widow(er) community nursing clients who are often aged and have functional impairment, is unknown. Systematic review. Current literature informs that the Geriatric Depression Scale accurately predicts a diagnosis of depression in community nursing cohorts. The three Depression Anxiety Stress Scales subscales of depression, anxiety and stress are valid; however, no studies were identified that compared the performance of the Depression Anxiety Stress Scales in predicting diagnoses of depression or anxiety. The Post-traumatic Stress Disorder Checklist predicts post-traumatic stress disorder in community cohorts although no studies meeting the selection criteria included male participants. This review provides recommendations for the use of the Geriatric Depression Scale, Depression Anxiety Stress Scales and The Post-traumatic Stress Disorder Checklist based on examination of the published evidence for the application of these screening tools in samples approximated to community nursing cohorts. Findings and recommendations would guide community nurses, managers and health planners in the selection of mental health screening tools to promote holistic community nursing care.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases.

PubMed

Liu, Peng; Wang, Boshi; Yan, Xia; Cai, Jingjing; Wang, Yu

2016-12-01

To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms. After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT. Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.

Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

PubMed

Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

2018-03-22

Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers. To discover broad-spectrum PTEN-SSL genes in breast cancer, we used a multi-step approach that started with (1) a genome-wide short interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast cancer cell lines; we then determined reproducibility of hits by (3) identification of overlaps between our results and reanalyzed data from 3 independent gene-essentiality screens, and finally, for selected candidate PTEN-SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity experiments in a panel of 19 cell lines or mutual exclusivity analysis of publicly available pan-cancer somatic mutation data. The screens (steps 1 and 2) and the reproducibility analysis (step 3) identified six candidate broad-spectrum PTEN-SSL genes (PIK3CB, ADAMTS20, AP1M2, HMMR, STK11, and NUAK1). PIK3CB was previously identified as PTEN-SSL, while the other five genes represent novel PTEN-SSL candidates. Confirmation studies (step 4) provided additional evidence that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01-015 selectively impaired viability in multiple PTEN-deficient breast cancer cell lines, while mutations affecting STK11 and PTEN were largely mutually exclusive across large pan-cancer data sets. Six genes showed PTEN-SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

Frequent binge drinking five to six years after exposure to 9/11: Findings from the World Trade Center Health Registry

PubMed Central

Welch, Alice E.; Caramanica, Kimberly; Maslow, Carey B.; Cone, James E.; Farfel, Mark R.; Keyes, Katherine M.; Stellman, Steven D.; Hasin, Deborah S.

2014-01-01

Background Exposure to 9/11 may have considerable long-term impact on health behaviors, including increased alcohol consumption. We examined the association between frequent binge drinking, posttraumatic stress disorder (PTSD), and number of 9/11-specific experiences among World Trade Center Health Registry (Registry) enrollees five-to-six years after 9/11. Methods Participants included 41,284 lower Manhattan residents, workers, passers-by, and rescue/recovery workers aged 18 or older without a pre-9/11 PTSD diagnosis who completed Wave 1 (2003–2004) and Wave 2 (2006–2007) interviews. Frequent binge drinking was defined as consuming five or more drinks on five or more occasions in the prior 30 days at Wave 2. Probable PTSD was defined as scoring 44 or greater on the PTSD Checklist. 9/11 exposure was measured as the sum of 12 experiences and grouped as none/low (0–1), medium (2–3), high (4–5) and very high (6+). Results Frequent binge drinking was significantly associated with increasing 9/11 exposure and PTSD. Those with very high and high exposures had a higher prevalence of frequent binge drinking (13.7% and 9.8%, respectively) than those with medium and low exposures (7.5% and 4.4%, respectively). Upon stratification, very high and high exposures were associated with frequent binge drinking in both the PTSD and no PTSD subgroups. Conclusions Our findings suggest that 9/11 exposure had an impact on frequent binge drinking five-to-six years later among Registry enrollees. Understanding the effects of traumatic exposure on alcohol use is important to identify risk factors for post-disaster alcohol misuse, inform policy, and improve post-disaster psychological and alcohol screening and counseling. PMID:24831753

Systematic screening of common wastewater-marking pharmaceuticals in urban aquatic environments: implications for environmental risk control.

PubMed

Zhou, Haidong; Zhang, Qingjun; Wang, Xuelian; Zhang, Qianqian; Ma, Lixin; Zhan, Yong

2014-01-01

In this report, we refer to pharmaceuticals that are widespread in the urban aquatic environment and that mainly originate from wastewater treatment plants or non-point source sewage as "wastewater-marking pharmaceuticals" (WWMPs). To some extent, they reflect the condition or trend of water contamination and also contribute to aquatic environmental risk assessment. The method reported here for screening typical WWMPs was proposed based on academic concerns about them and their concentrations present in the urban aquatic environment, as well as their properties of accumulation, persistence, eco-toxicity and related environmental risks caused by them. The screening system consisted of an initial screening system and a further screening system. In the former, pharmaceuticals were categorised into different evaluation levels, and in the latter, each pharmaceutical was given a normalised final evaluation score, which was the sum of every score for its properties of accumulation, persistence, eco-toxicity and environmental risk in the aquatic environment. The system was applied to 126 pharmaceuticals frequently detected in the aquatic environment. In the initial screening procedure, five pharmaceuticals were classified into the "high" category, 16 pharmaceuticals into the "medium" category, 15 pharmaceuticals into the "low" category and 90 pharmaceuticals into the "very low" category. Subsequently, further screening were conducted on 36 pharmaceuticals considered as being of "high", "medium" and "low" categories in the former system. We identified 7 pharmaceuticals with final evaluation scores of 1-10, 10 pharmaceuticals with scores of 11-15, 15 pharmaceuticals with scores from 16 to 20 and 4 pharmaceuticals with scores above 21. The results showed that this screening system could contribute to the effective selection of target WWMPs, which would be important for spatial-temporal dynamics, transference and pollution control of pharmaceuticals in the urban aquatic environment. However, there remains a number of pharmaceutical parameters with measured data gaps, such as organic carbon adsorption coefficients and bioconcentration factors, which, if filled, would improve the accuracy of the screening system.

The Work Ability Index as a screening tool to identify the need for rehabilitation: longitudinal findings from the Second German Sociomedical Panel of Employees.

PubMed

Bethge, Matthias; Radoschewski, Friedrich Michael; Gutenbrunner, Christoph

2012-11-01

To evaluate the predictive value of the Work Ability Index (WAI) for different indicators of the need for rehabilitation at 1-year follow-up. Cohort study. Data were obtained from the Second German Sociomedical Panel of Employees, a large-scale cohort study with postal surveys in 2009 and 2010. A total of 457 women and 579 men were included. Confirmatory factor analysis confirmed the one-dimensionality of the WAI. Regression analyses showed that poor and moderate baseline WAI scores were associated with lower health-related quality of life and more frequent use of primary healthcare 1 year later. Subjects with poor baseline work ability had 4.6 times higher odds of unemployment and 12.2 times higher odds of prolonged sick leave than the reference group with good or excellent baseline work ability. Moreover, the odds of subjectively perceived need for rehabilitation, intention to request rehabilitation and actual use of rehabilitation services were 9.7, 5.7 and 3 times higher in the poor baseline WAI group and 5.5, 4 and 1.8 times higher in the moderate baseline WAI group, respectively. A WAI score ≤ 37 was identified as the optimal cut-off to predict the need for rehabilitation. The WAI is a valid screening tool for identifying the need for rehabilitation.

Development and Evaluation of a Magnetic Immunochromatographic Test To Detect Taenia solium, Which Causes Taeniasis and Neurocysticercosis in Humans▿

PubMed Central

Handali, Sukwan; Klarman, Molly; Gaspard, Amanda N.; Dong, X. Fan; LaBorde, Ronald; Noh, John; Lee, Yeuk-Mui; Rodriguez, Silvia; Gonzalez, Armando E.; Garcia, Hector H.; Gilman, Robert H.; Tsang, Victor C. W.; Wilkins, Patricia P.

2010-01-01

Taeniasis/cysticercosis caused by Taenia solium is a frequent parasitic infection of the human brain in most of the world. Rapid and simple screening tools to identify taeniasis and cysticercosis cases are needed for control programs, mostly to identify tapeworm carriers which are the source of infection and need to be treated, or as tools for point-of-care case detection or confirmation. These screening assays should be affordable, reliable, rapid, and easy to perform. Immunochromatographic tests meet these criteria. To demonstrate proof of principle, we developed and evaluated two magnetic immunochromatographic tests (MICTs) for detection of human Taenia solium taeniasis antibodies (ES33-MICT) and neurocysticercosis antibodies (T24-MICT). These assays detected stage-specific antibodies by using two recombinant proteins, rES33 for detection of taeniasis antibodies and rT24H for detection of cysticercosis antibodies. The sensitivity and specificity of the ES33-MICT to detect taeniasis infections were 94.5% and 96%, respectively, and those of the T24-MICT to detect cases of human cysticercosis with two or more viable brain cysts were 93.9% and 98.9%, respectively. These data provide proof of principle that the ES33- and T24-MICTs provide rapid and suitable methods to identify individuals with taeniasis and cysticercosis. PMID:20181766

Title: Studies on drug switchability showed heterogeneity in methodological approaches: a scoping review.

PubMed

Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina

2018-05-16

Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.

Pathologic Findings of Breast Lesions Detected on Magnetic Resonance Imaging.

PubMed

Jabbar, Seema B; Lynch, Beverly; Seiler, Stephen; Hwang, Helena; Sahoo, Sunati

2017-11-01

- Breast magnetic resonance imaging (MRI) is now used routinely for high-risk screening and in the evaluation of the extent of disease in newly diagnosed breast cancer patients. Morphologic characteristics and the kinetic pattern largely determine how suspicious a breast lesion is on MRI. Because of its high sensitivity, MRI identifies a large number of suspicious lesions. However, the low to moderate specificity and the additional cost have raised questions regarding its frequent use. - To identify the pathologic entities that frequently present as suspicious enhancing lesions and to identify specific MRI characteristics that may be predictive of malignancy. - One hundred seventy-seven MRI-guided biopsies from 152 patients were included in the study. The indication for MRI, MRI features, pathologic findings, and patient demographics were recorded. The MRI findings and the pathology slides were reviewed by a dedicated breast radiologist and breast pathologists. - Seventy-one percent (126 of 177) of MRI-guided breast biopsies were benign, 11% (20 of 177) showed epithelial atypia, and 18% (31 of 177) showed malignancy. The vast majority (84%; 62 of 74) of MRI lesions with persistent kinetics were benign. However, 57% (17 of 30) of lesions with washout kinetics and 65% (62 of 95) of mass lesions were also benign. - Magnetic resonance imaging detects malignancies undetected by other imaging modalities but also detects a wide variety of benign lesions. Benign and malignant lesions identified by MRI share similar morphologic and kinetic features, necessitating biopsy for histologic confirmation.

Contact allergy to the 26 specific fragrance ingredients to be declared on cosmetic products in accordance with the EU cosmetics directive.

PubMed

Heisterberg, Maria V; Menné, Torkil; Johansen, Jeanne D

2011-11-01

Fragrance ingredients are a frequent cause of allergic contact dermatitis. The EU Cosmetics Directive states that 26 specific fragrance ingredients, known to cause allergic contact dermatitis, must be declared on the ingredient lists of cosmetic products. To investigate frequencies of sensitization to the 26 individual fragrances and evaluate their importance as screening markers of fragrance allergy. This was a retrospective study based on data from the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte. Eczema patients (n = 1508) were patch tested (January 2008 to July 2010) with the 26 fragrance ingredients. Sensitization to the 26 fragrances was identified in 115 (7.6%) subjects. The most frequent allergens were Evernia furfuracea (n = 50), Evernia prunastri (n = 31), and hydroxyisohexyl 3-cyclohexene carboxaldehyde (n = 24). Including fragrance mix I, fragrance mix II and Myroxylon pereirae, 196 (13.0%) had a fragrance allergy. Testing with the 26 fragrances additionally identified 23 subjects who would otherwise have gone undetected. The majority (75.7%) of positive reactions to the 26 fragrances were of clinical relevance. Sensitization to the 26 individual fragrance ingredients was identified in 7.6% of the subjects patch tested. Most reactions were of clinical relevance. Fragrance-allergic subjects would be missed if testing with the individual fragrance ingredients was not performed. © 2011 John Wiley & Sons A/S.

SUBSTANCE USE SCREENING AND INTERVENTIONS IN DENTAL CLINICS: SURVEY OF PRACTICE-BASED RESEARCH NETWORK DENTISTS ON CURRENT PRACTICES, POLICIES, AND BARRIERS

PubMed Central

Wright, Shana; Matthews, Abigail G.; Rotrosen, John; Shelley, Donna; Buchholz, Matthew P.; Curro, Frederick A.

2013-01-01

Background Dental visits represent an opportunity to identify and assist patients with substance use, but little is known about how dentists are addressing tobacco, alcohol and illicit drugs. We surveyed dentists to learn about the role their practices might play in providing substance use screening and interventions. Methods A 41-item, web-based survey was distributed to all 210 dentists active in the PEARL dental practice-based research network. The questionnaire assessed clinic policies and current practices, attitudes, and perceived barriers to providing services for tobacco, alcohol, and illicit drug use. Results 143 dentists completed the survey (68% response rate). While screening was common, fewer were providing follow-up counseling or referrals for substance use. Insufficient knowledge/training was the most frequently cited barrier to intervention. Many dentists said they would offer assistance for tobacco (67%) or alcohol or illicit drugs (52%) if reimbursed; an affirmative response was more likely among those who saw publicly insured patients. Conclusions Dentists recognize the importance of screening for substance use, but lack clinical training and systems that could facilitate intervention. Practice Implications If barriers were reduced through changes in reimbursement, education, and systems-level support, our findings indicate that dentists may be willing to address substance use, including use of alcohol and illicit drugs as well as tobacco. PMID:23729460

Relationship between body image and breast self-examination intentions and behavior among female university students in Malaysia.

PubMed

Samah, Asnarulkhadi Abu; Ahmadian, Maryam

2014-01-01

This study aimed to examine the relationship between body image satisfaction and breast self-screening behavior and intentions. The sample for this cross-sectional study consisted of 842 female university students who were recruited from a number of public and private universities. Data were obtained between the months of November and December, 2013, using multistage random cluster sampling. Main research variables were breast cancer screening behavior and intentions, demographic factors, and the total scores on each of the Multidimensional Body-Self Relations Questionnaire (MBSRQ-Appearance Scales) subscales. Results of multivariate analysis showed that having higher satisfaction and more positive evaluation of appearance were related to having performed breast self-examination more frequently in the last year and intending to perform breast self-examination more frequently in the next year. Longitudinal research can potentially provide detailed information about overall body image satisfaction and breast cancer screening behavior among various communities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shatsky, Maxim; Allen, Simon; Gold, Barbara

Numerous affinity purification – mass-spectrometry (AP-MS) and yeast two hybrid (Y2H) screens have each defined thousands of pairwise protein-protein interactions (PPIs), most between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial Y2H and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared to the nine published interactomes, our two networks are smaller; are much less highly connected; have significantly lower false discovery rates; and are much moremore » enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays. Lastly, our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested.« less

Use of Electrocardiogram as Part of the Preparticipation Examination.

PubMed

Chain, Kelly; Gregory, Andrew

2016-01-01

A sudden cardiac event or death in a young athlete is a traumatic and memorable event. These tragic events have long-lasting and widespread influences that not only affect the person's immediate family, but also have profound effects on the team, school, and entire community. Over the past several decades there has been a significant research effort in the area of sudden cardiac death (SCD) in athletes in hopes of decreasing preventable deaths. One area of research and discussion that has emerged is the use of electrocardiograms (EKGs) in preparticipation screening examinations as a tool to help identify athletes at risk for SCD. The use of an EKG in addition to a detailed history and physical examination is a controversial and frequently debated topic. To help sort through some of the controversy, this article discusses some of the pros and cons of incorporating the EKG as a screening modality in the preparticipation evaluation for clearance to participate in sports. Copyright 2016, SLACK Incorporated.

Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

PubMed Central

Neumann, M. A.; van de Streek, J.; Fabbiani, F. P. A.; Hidber, P.; Grassmann, O.

2015-01-01

Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination with rationally planned crystallization experiments to study the polymorphism of the pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of the most flexible molecules ever studied computationally. The experimental crystal polymorphs are found at the bottom of the calculated lattice energy landscape, and two predicted structures are identified as candidates for a missing, thermodynamically more stable polymorph. Pressure-dependent stability calculations suggested high pressure as a means to bring these polymorphs into existence. Subsequently, one of them could indeed be crystallized in the 0.02 to 0.50 GPa pressure range and was found to be metastable at ambient pressure, effectively derisking the appearance of a more stable polymorph during late-stage development of Dalcetrapib. PMID:26198974

Cancer-Related Fatigue, Version 2.2015

PubMed Central

Berger, Ann M.; Mooney, Kathi; Alvarez-Perez, Amy; Breitbart, William S.; Carpenter, Kristen M.; Cella, David; Cleeland, Charles; Dotan, Efrat; Eisenberger, Mario A.; Escalante, Carmen P.; Jacobsen, Paul B.; Jankowski, Catherine; LeBlanc, Thomas; Ligibel, Jennifer A.; Loggers, Elizabeth Trice; Mandrell, Belinda; Murphy, Barbara A.; Palesh, Oxana; Pirl, William F.; Plaxe, Steven C.; Riba, Michelle B.; Rugo, Hope S.; Salvador, Carolina; Wagner, Lynne I.; Wagner-Johnston, Nina D.; Zachariah, Finly J.; Bergman, Mary Anne; Smith, Courtney

2017-01-01

Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer. PMID:26285247

Kinase inhibitor profiling reveals unexpected opportunities to inhibit disease-associated mutant kinases

PubMed Central

Duong-Ly, Krisna C.; Devarajan, Karthik; Liang, Shuguang; Horiuchi, Kurumi Y.; Wang, Yuren; Ma, Haiching; Peterson, Jeffrey R.

2016-01-01

Summary Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant, mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases including ALK, LRRK2, RET, and EGFR as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development. PMID:26776524

School-Based Screening to Identify At-Risk Students Not Already Known to School Professionals: The Columbia Suicide Screen

PubMed Central

Wilcox, Holly C.; Schonfeld, Irvin Sam; Davies, Mark; Hicks, Roger C.; Turner, J. Blake; Shaffer, David

2009-01-01

Objectives. We sought to determine the degree of overlap between students identified through school-based suicide screening and those thought to be at risk by school administrative and clinical professionals. Methods. Students from 7 high schools in the New York metropolitan area completed the Columbia Suicide Screen; 489 of the 1729 students screened had positive results. The clinical status of 641 students (73% of those who had screened positive and 23% of those who had screened negative) was assessed with modules from the Diagnostic Interview Schedule for Children. School professionals nominated by their principal and unaware of students' screening and diagnostic status were asked to indicate whether they were concerned about the emotional well-being of each participating student. Results. Approximately 34% of students with significant mental health problems were identified only through screening, 13.0% were identified only by school professionals, 34.9% were identified both through screening and by school professionals, and 18.3% were identified neither through screening nor by school professionals. The corresponding percentages among students without mental health problems were 9.1%, 24.0%, 5.5%, and 61.3%. Conclusions. School-based screening can identify suicidal and emotionally troubled students not recognized by school professionals. PMID:19059865

On the microbiological profile of traditional Portuguese sourdough.

PubMed

Rocha, J M; Malcata, F X

1999-12-01

Traditional manufacture of bread from maize has been noted to play important roles from both economic and social standpoints; however, enforcement of increasingly strict hygiene standards requires thorough knowledge of the adventitious microbiota of the departing dough. To this goal, sourdough as well as maize and rye flours from several geographic locations and in two different periods within the agricultural year were assayed for their microbiota in sequential steps of quantification and identification. More than 400 strains were isolated and taxonomic differentiation between them was via Biomerieux API galleries (375 of which were successfully identified) following preliminary biochemical and morphological screening. The dominant groups were yeasts and lactic acid bacteria (LAB). The most frequently isolated yeasts were Saccharomyces cerevisiae and Candida pelliculosa. The most frequently isolated LAB were (heterofermentative) Leuconostoc spp. and (homofermentative) Lactobacillus spp.; L. brevis, L. curvatus, and L. lactis ssp. lactis were the dominant species for the Lactobacillus genera; Lactococcus lactis ssp. lactis for lactococci; Enterococcus casseliflavus, E. durans, and E. faecium for enterococci; and Streptococcus constellantus and S. equinus for streptococci.

Analysis of Peer Interaction in Learning Activities with Personal Handhelds and Shared Displays

ERIC Educational Resources Information Center

Liu, Chen-Chung; Chung, Chen-Wei; Chen, Nian-Shing; Liu, Baw-Jhiune

2009-01-01

Collaborative learning is extensively applied in classroom activities, but the screens on handheld devices are designed for individual-user mobile applications and may constrain interaction among group learners. The small screen size may lead to fragmented and tete-a-tete communication patterns and frequently obstruct the externalization of the…

Validity and Reliability of Psychosocial Factors Related to Breast Cancer Screening.

ERIC Educational Resources Information Center

Zapka, Jane G.; And Others

1991-01-01

The construct validity of hypothesized survey items and data reduction procedures for selected psychosocial constructs frequently used in breast cancer screening research were investigated in telephone interviews with randomly selected samples of 1,184 and 903 women and a sample of 169 Hispanic clinic clients. Validity of the constructs is…

Skin cancer beliefs, knowledge, and prevention practices: a comparison of farmers and nonfarmers in a midwestern population.

PubMed

Carley, Alexandra; Stratman, Erik

2015-01-01

Farmers have substantial sun exposure and increased skin cancer risk but poor sun protection practices. There are few studies regarding the underlying factors that contribute to inadequate skin cancer prevention practices in the farming population, and minimal data to guide skin cancer awareness and educational interventions for this population. The purpose of this study was to assess skin cancer knowledge, sun protection behaviors and barriers, health care information sources, and the impact of skin cancer screening among midwestern farmers and nonfarmers. Individuals attending a free skin cancer screening during 2011 Wisconsin Farm Technology Days were surveyed for self-reported sun protection use, extent of sun exposure, and skin cancer and sun protection beliefs and knowledge. A total of 476 individuals participated in the study, including 194 farmers. Although farmers identified sun protection benefits, few reported optimal practices, with only 23% of farmers reporting sunscreen use always or frequently when out in the sun for 15 minutes or more. Common barriers to sun protection included discomfort with wearing long pants and long shirts, forgetfulness with sunscreen use, and inconvenience with wearing wide-brimmed hats. Higher knowledge scores in farmers were associated with better sun protection. Farmers utilized different sources of health care information compared with nonfarmers, including farm magazines and newspapers, radio, and farm organizations. Providers should consider the unique characteristics of the farming population to provide skin cancer prevention education that is tailored to the needs of this population, such as reminders for sunscreen use and resources for sun-protective hats that do not interfere with work. Among individuals without prior history of skin cancer, 34% of farmers and 22% of nonfarmers (P = .0127) were referred for additional evaluation due to identification of a concerning lesion at the screening event. Thus, farmers may preferentially benefit from skin cancer screening events, and this population should be targeted for additional screening events in the future. This study identifies unique characteristics of the farming population that can assist providers in caring for this population and guide the future development of skin cancer awareness, prevention, and screening initiatives to benefit farmers.

High School Bullying as a Risk for Later Depression and Suicidality

ERIC Educational Resources Information Center

Klomek, Anat Brunstein; Kleinman, Marjorie; Altschuler, Elizabeth; Marrocco, Frank; Amakawa, Lia; Gould, Madelyn S.

2011-01-01

This is the first study to examine whether high school students experiencing frequent bullying behaviors are at risk for "later" depression and suicidality. A total of 236 students who reported frequent bullying behavior without depression or suicidality during a suicide screening were interviewed 4 years later to reassess depression, suicidal…

Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

PubMed

Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

2016-01-01

Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0.05), two, SPOP and ZNF671, close to statistical significance (p = 0.051 and 0.076). We provide evidence of an inflammation-specific autoantibody profile and confirm the expression of corresponding autoantigens in prostate tissue. This supports evaluation of autoantibodies as non-invasive markers for prostate inflammation.

Identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system.

PubMed

Osorio, Yaneth; Travi, Bruno L; Renslo, Adam R; Peniche, Alex G; Melby, Peter C

2011-02-15

New drugs are needed to treat visceral leishmaniasis (VL) because the current therapies are toxic, expensive, and parasite resistance may weaken drug efficacy. We established a novel ex vivo splenic explant culture system from hamsters infected with luciferase-transfected Leishmania donovani to screen chemical compounds for anti-leishmanial activity. THIS MODEL HAS ADVANTAGES OVER IN VITRO SYSTEMS IN THAT IT: 1) includes the whole cellular population involved in the host-parasite interaction; 2) is initiated at a stage of infection when the immunosuppressive mechanisms that lead to progressive VL are evident; 3) involves the intracellular form of Leishmania; 4) supports parasite replication that can be easily quantified by detection of parasite-expressed luciferase; 5) is adaptable to a high-throughput screening format; and 6) can be used to identify compounds that have both direct and indirect anti-parasitic activity. The assay showed excellent discrimination between positive (amphotericin B) and negative (vehicle) controls with a Z' Factor >0.8. A duplicate screen of 4 chemical libraries containing 4,035 compounds identified 202 hits (5.0%) with a Z score of <-1.96 (p<0.05). Eighty-four (2.1%) of the hits were classified as lead compounds based on the in vitro therapeutic index (ratio of the compound concentration causing 50% cytotoxicity in the HepG(2) cell line to the concentration that caused 50% reduction in the parasite load). Sixty-nine (82%) of the lead compounds were previously unknown to have anti-leishmanial activity. The most frequently identified lead compounds were classified as quinoline-containing compounds (14%), alkaloids (10%), aromatics (11%), terpenes (8%), phenothiazines (7%) and furans (5%). The ex vivo splenic explant model provides a powerful approach to identify new compounds active against L. donovani within the pathophysiologic environment of the infected spleen. Further in vivo evaluation and chemical optimization of these lead compounds may generate new candidates for preclinical studies of treatment for VL.

Detecting the severity of perinatal anxiety with the Perinatal Anxiety Screening Scale (PASS).

PubMed

Somerville, Susanne; Byrne, Shannon L; Dedman, Kellie; Hagan, Rosemary; Coo, Soledad; Oxnam, Elizabeth; Doherty, Dorota; Cunningham, Nadia; Page, Andrew C

2015-11-01

The Perinatal Anxiety Screening Scale (PASS; Somerville et al., 2014) reliably identifies perinatal women at risk of problematic anxiety when a clinical cut-off score of 26 is used. This study aimed to identify a severity continuum of anxiety symptoms with the PASS to enhance screening, treatment and research for perinatal anxiety. Antenatal and postnatal women (n=410) recruited from the antenatal clinics and mental health services at an obstetric hospital completed the Edinburgh Postnatal Depression Scale (EPDS), the Depression, Anxiety and Stress Scale (DASS-21), the Spielberg State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory II (BDI), and the PASS. The women referred to mental health services were assessed to determine anxiety diagnoses via a diagnostic interview conducted by an experienced mental health professional from the Department of Psychological Medicine - King Edward Memorial Hospital. Three normative groups for the PASS, namely minimal anxiety, mild-moderate anxiety, and severe anxiety, were identified based on the severity of anxiety indicated on the standardised scales and anxiety diagnoses. Two cut-off points for the normative groups were calculated using the Jacobson-Truax method (Jacobson and Truax, 1991) resulting in three severity ranges: 'minimal anxiety'; 'mild-moderate anxiety'; and 'severe anxiety'. The most frequent diagnoses in the study sample were adjustment disorder, mixed anxiety and depression, generalised anxiety, and post-traumatic stress disorder. This may limit the generalisability of the severity range results to other anxiety diagnoses including obsessive compulsive disorder and specific phobia. Severity ranges for the PASS add value to having a clinically validated cut-off score in the detection and monitoring of problematic perinatal anxiety. The PASS can now be used to identify risk of an anxiety disorder and the severity ranges can indicate developing risk for early referrals for further assessments, prioritisation of access to resources and tracking of clinically significant deterioration, improvement or stability in anxiety over time. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

PubMed Central

Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

2016-01-01

Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0.05), two, SPOP and ZNF671, close to statistical significance (p = 0.051 and 0.076). Conclusions We provide evidence of an inflammation-specific autoantibody profile and confirm the expression of corresponding autoantigens in prostate tissue. This supports evaluation of autoantibodies as non-invasive markers for prostate inflammation. PMID:26863016

Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy.

PubMed

Burlina, Alberto B; Polo, Giulia; Salviati, Leonardo; Duro, Giovanni; Zizzo, Carmela; Dardis, Andrea; Bembi, Bruno; Cazzorla, Chiara; Rubert, Laura; Zordan, Roberta; Desnick, Robert J; Burlina, Alessandro P

2018-03-01

Lysosomal storage diseases (LSDs) are inborn errors of metabolism resulting from 50 different inherited disorders. The increasing availability of treatments and the importance of early intervention have stimulated newborn screening (NBS) to diagnose LSDs and permit early intervention to prevent irreversible impairment or severe disability. We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases. Activities of acid β-glucocerebrosidase (ABG; Gaucher), acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), and acid α-L-iduronidase (IDUA; MPS-I) in dried blood spots (DBS) from all newborns during a 17-month period were determined by multiplexed tandem mass spectrometry (MS/MS) using the NeoLSD ® assay system. Enzymatic activity cutoff values were determined from 3500 anonymous newborn DBS. In the screening study, samples were retested if the value was below cutoff and a second spot was requested, with referral for confirmatory testing and medical evaluation if a low value was obtained. From September 2015 to January 2017, 44,411 newborns were screened for the four LSDs. We recalled 40 neonates (0.09%) for collection of a second DBS. Low activity was confirmed in 20, who had confirmatory testing. Ten of 20 had pathogenic mutations: two Pompe, two Gaucher, five Fabry, and one MPS-I. The incidences of Pompe and Gaucher diseases were similar (1/22,205), with Fabry disease the most frequent (1/8882) and MPS-I the rarest (1/44411). The combined incidence of the four disorders was 1/4411 births. Simultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program.

Digital Solutions for Informed Decision Making: An Academic-Community Partnership for the Development of a Prostate Cancer Decision Aid for African American Men.

PubMed

Owens, Otis L; Friedman, Daniela B; Brandt, Heather M; Bernhardt, Jay M; Hébert, James R

2016-05-01

African American (AA) men are significantly more likely to die of prostate cancer (PrCA) than other racial groups, and there is a critical need to identify strategies for providing information about PrCA screening and the importance of informed decision making (IDM). To assess whether a computer-based IDM intervention for PrCA screening would be appropriate for AA men, this formative evaluation study examined their (1) PrCA risk and screening knowledge; (2) decision-making processes for PrCA screening; (3) usage of, attitudes toward, and access to interactive communication technologies (ICTs); and (4) perceptions regarding a future, novel, computer-based PrCA education intervention. A purposive convenience sample of 39 AA men aged 37 to 66 years in the Southeastern United States was recruited through faith-based organizations to participate in one of six 90-minute focus groups and complete a 45-item descriptive survey. Participants were generally knowledgeable about PrCA. However, few engaged in IDM with their doctor and few were informed about the associated risks and uncertainties of PrCA screening. Most participants used ICTs on a daily basis for various purposes including health information seeking. Most participants were open to a novel, computer-based intervention if the system was easy to use and its animated avatars were culturally appropriate. Because study participants had low exposure to IDM for PrCA, but frequently used ICTs, IDM interventions using ICTs (e.g., computers) hold promise for AA men and should be explored for feasibility and effectiveness. These interventions should aim to increase PrCA screening knowledge and stress the importance of participating in IDM with doctors. © The Author(s) 2015.

Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants.

PubMed

Göpel, Wolfgang; Berkowski, Sandra; Preuss, Michael; Ziegler, Andreas; Küster, Helmut; Felderhoff-Müser, Ursula; Gortner, Ludwig; Mögel, Michael; Härtel, Christoph; Herting, Egbert

2014-08-26

The mitochondrial m.1555A>G mutation is associated with a high rate of permanent hearing loss, if aminoglycosides are given. Preterm infants have an increased risk of permanent hearing loss and are frequently treated with aminoglycoside antibiotics. We genotyped preterm infants with a birth weight below 1500 grams who were prospectively enrolled in a large cohort study for the m.1555A>G mutation. Treatment with aminoglycoside antibiotics in combination with mitochondrial m.1555A>G mutation was tested as a predictor for failed hearing screening at discharge in a multivariate logistic regression analysis. 7056 infants were genotyped and analysed. Low birth weight was the most significant predictor of failed hearing screening (p = 7.3 × 10-10). 12 infants (0.2%) had the m.1555A>G-mutation. In a multivariable logistic regression analysis, the combination of aminoglycoside treatment with m.1555A>G-carrier status was associated with failed hearing screening (p = 0.0058). However, only 3 out of 10 preterm m.1555A>G-carriers who were exposed to aminoglycosides failed hearing screening. The m.1555A>G-mutation was detected in all mothers of m.1555A>G-positive children, but in none of 2993 maternal DNA-samples of m.1555A>G-negative infants. Antenatal screening for the m.1555A>G mutation by maternal genotyping of pregnant women with preterm labour might be a reasonable approach to identify infants who are at increased risk for permanent hearing loss. Additional studies are needed to estimate the relevance of cofactors like aminoglycoside plasma levels and birth weight and the amount of preterm m.1555A>G-carriers with permanent hearing loss.

Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants

PubMed Central

2014-01-01

Background The mitochondrial m.1555A>G mutation is associated with a high rate of permanent hearing loss, if aminoglycosides are given. Preterm infants have an increased risk of permanent hearing loss and are frequently treated with aminoglycoside antibiotics. Methods We genotyped preterm infants with a birth weight below 1500 grams who were prospectively enrolled in a large cohort study for the m.1555A>G mutation. Treatment with aminoglycoside antibiotics in combination with mitochondrial m.1555A>G mutation was tested as a predictor for failed hearing screening at discharge in a multivariate logistic regression analysis. Results 7056 infants were genotyped and analysed. Low birth weight was the most significant predictor of failed hearing screening (p = 7.3 × 10-10). 12 infants (0.2%) had the m.1555A>G-mutation. In a multivariable logistic regression analysis, the combination of aminoglycoside treatment with m.1555A>G-carrier status was associated with failed hearing screening (p = 0.0058). However, only 3 out of 10 preterm m.1555A>G-carriers who were exposed to aminoglycosides failed hearing screening. The m.1555A>G-mutation was detected in all mothers of m.1555A>G-positive children, but in none of 2993 maternal DNA-samples of m.1555A>G-negative infants. Conclusion Antenatal screening for the m.1555A>G mutation by maternal genotyping of pregnant women with preterm labour might be a reasonable approach to identify infants who are at increased risk for permanent hearing loss. Additional studies are needed to estimate the relevance of cofactors like aminoglycoside plasma levels and birth weight and the amount of preterm m.1555A>G-carriers with permanent hearing loss. PMID:25155176

Screening for confabulations with the confabulation screen.

PubMed

Dalla Barba, Gianfranco; Brazzarola, Marta; Marangoni, Sara; La Corte, Valentina

2018-04-24

The objective of this work is to devise and validate a sensitive and specific test for confabulatory impairment. We conceived a screening test for confabulation, the Confabulation Screen (CS), a brief test using 10 questions of episodic memory (EM), where confabulators most frequently confabulate. It was postulated that the CS would predict confabulations not only in EM, but also in the other subordinate structures of personal temporality, namely the present and the future. Thirty confabulating amnesic patients of various aetiologies and 97 normal controls entered the study. Participants were administered the CS and the Confabulation Battery (Dalla Barba, G., & Decaix, C. (2009). "Do you remeber what you did on March 13 1985?" A case study of confabulatory hypermnesia. Cortex, 45(5), 566-574). Confabulations in the CS positively and significantly correlated with confabulations in personal temporality domains of the CB, namely EM, orientation in time and place and episodic plans. Conversely, as expected, they did not correlate with confabulations in impersonal temporality domains of the CB. Consistent with results of previous studies, the most frequently observed type of confabulation in the CS was Habits Confabulation. The CS had high construct validity and good discriminative validity in terms of sensitivity and specificity. Cut-off scores for clinical and research purposes are proposed. The CS provides efficient and valid screening for confabulatory impairment.

Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals.

PubMed

Holme, Øyvind; Bretthauer, Michael; Fretheim, Atle; Odgaard-Jensen, Jan; Hoff, Geir

2013-10-01

Colorectal cancer is the third most frequent cancer in the world. As the sojourn time for this cancer is several years and a good prognosis is associated with early stage diagnosis, screening has been implemented in a number of countries. Both screening with faecal occult blood test and flexible sigmoidoscopy have been shown to reduce mortality from colorectal cancer in randomised controlled trials. The comparative effectiveness of these tests on colorectal cancer mortality has, however, never been evaluated, and controversies exist over which test to choose. To compare the effectiveness of screening for colorectal cancer with flexible sigmoidoscopy to faecal occult blood testing. We searched MEDLINE and EMBASE (November 16, 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11) and reference lists for eligible studies. Randomised controlled trials comparing screening with flexible sigmoidoscopy or faecal occult blood testing to each other or to no screening. Only studies reporting mortality from colorectal cancer were included. Faecal occult blood testing had to be repeated (annually or biennially). Data retrieval and assessment of risk of bias were performed independently by two review authors. Standard meta-analyses using a random-effects model were conducted for flexible sigmoidoscopy and faecal occult blood testing (FOBT) separately and we calculated relative risks with 95% confidence intervals (CI). We used a Bayesian approach (a contrast-based network meta-analysis method) for indirect analyses and presented the results as posterior median relative risk with 95% credibility intervals. We assessed the quality of evidence using GRADE. We identified nine studies comprising 338,467 individuals randomised to screening and 405,919 individuals to the control groups. Five studies compared flexible sigmoidoscopy to no screening and four studies compared repetitive guaiac-based FOBT (annually and biennially) to no screening. We did not consider that study risk of bias reduced our confidence in our results. We did not identify any studies comparing the two screening methods directly. When compared with no screening, colorectal cancer mortality was lower with flexible sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence) and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the analyses based on indirect comparison of the two screening methods, the relative risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to 1.01, low quality evidence) for flexible sigmoidoscopy screening compared to FOBT. No complications occurred after the FOBT test itself, but 0.03% of participants suffered a major complication after follow-up. Among more than 60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up colonoscopies, a major complication was recorded in 0.08% of participants. Adverse event data should be interpreted with caution as the reporting of adverse effects was incomplete. There is high quality evidence that both flexible sigmoidoscopy and faecal occult blood testing reduce colorectal cancer mortality when applied as screening tools. There is low quality indirect evidence that screening with either approach reduces colorectal cancer deaths more than the other. Major complications associated with screening require validation from studies with more complete reporting of harms

The radiological features, diagnosis and management of screen-detected lobular neoplasia of the breast: Findings from the Sloane Project.

PubMed

Maxwell, Anthony J; Clements, Karen; Dodwell, David J; Evans, Andrew J; Francis, Adele; Hussain, Monuwar; Morris, Julie; Pinder, Sarah E; Sawyer, Elinor J; Thomas, Jeremy; Thompson, Alastair

2016-06-01

To investigate the radiological features, diagnosis and management of screen-detected lobular neoplasia (LN) of the breast. 392 women with pure LN alone were identified within the prospective UK cohort study of screen-detected non-invasive breast neoplasia (the Sloane Project). Demography, radiological features and diagnostic and therapeutic procedures were analysed. Non-pleomorphic LN (369/392) was most frequently diagnosed among women aged 50-54 and in 53.5% was at the first screen. It occurred most commonly on the left (58.0%; p = 0.003), in the upper outer quadrant and confined to one site (single quadrant or retroareolar region). No bilateral cases were found. The predominant radiological feature was microcalcification (most commonly granular) which increased in frequency with increasing breast density. Casting microcalcification as a predominant feature had a significantly higher lesion size compared to granular and punctate patterns (p = 0.034). 326/369 (88.3%) women underwent surgery, including 17 who underwent >1 operation, six who had mastectomy and six who had axillary surgery. Two patients had radiotherapy and 15 had endocrine treatment. Pleomorphic lobular carcinoma in situ (23/392) presented as granular microcalcification in 12; four women had mastectomy and six had radiotherapy. Screen-detected LN occurs in relatively young women and is predominantly non-pleomorphic and unilateral. It is typically associated with granular or punctate microcalcification in the left upper outer quadrant. Management, including surgical resection, is highly variable and requires evidence-based guideline development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology.

PubMed

Minden, Sarah L; Feinstein, Anthony; Kalb, Rosalind C; Miller, Deborah; Mohr, David C; Patten, Scott B; Bever, Christopher; Schiffer, Randolph B; Gronseth, Gary S; Narayanaswami, Pushpa

2014-01-14

To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population.

Measuring the Pain Area: An Intra- and Inter-Rater Reliability Study Using Image Analysis Software.

PubMed

Dos Reis, Felipe Jose Jandre; de Barros E Silva, Veronica; de Lucena, Raphaela Nunes; Mendes Cardoso, Bruno Alexandre; Nogueira, Leandro Calazans

2016-01-01

Pain drawings have frequently been used for clinical information and research. The aim of this study was to investigate intra- and inter-rater reliability of area measurements performed on pain drawings. Our secondary objective was to verify the reliability when using computers with different screen sizes, both with and without mouse hardware. Pain drawings were completed by patients with chronic neck pain or neck-shoulder-arm pain. Four independent examiners participated in the study. Examiners A and B used the same computer with a 16-inch screen and wired mouse hardware. Examiner C used a notebook with a 16-inch screen and no mouse hardware, and Examiner D used a computer with an 11.6-inch screen and a wireless mouse. Image measurements were obtained using GIMP and NIH ImageJ computer programs. The length of all the images was measured using GIMP software to a set scale in ImageJ. Thus, each marked area was encircled and the total surface area (cm(2) ) was calculated for each pain drawing measurement. A total of 117 areas were identified and 52 pain drawings were analyzed. The intrarater reliability between all examiners was high (ICC = 0.989). The inter-rater reliability was also high. No significant differences were observed when using different screen sizes or when using or not using the mouse hardware. This suggests that the precision of these measurements is acceptable for the use of this method as a measurement tool in clinical practice and research. © 2014 World Institute of Pain.

Statistical Test for Latent Growth Nonlinearity with Three Time Points. Research Brief 8

ERIC Educational Resources Information Center

Nese, Joseph F. T.

2013-01-01

Curriculum-based measurement (CBM) is a system of assessment used to screen for students at risk for poor learning. CBM benchmark screening assessments are typically administered to all students in the fall, winter, and spring, and these data are frequently used by researchers to model and perhaps explain within-year growth. Modeling growth with…

Methylomic Analysis Identifies Frequent DNA Methylation of Zinc Finger Protein 582 (ZNF582) in Cervical Neoplasms

PubMed Central

Su, Po-Hsuan; Chen, Yu-Chih; Liao, Yu-Ping; Wang, Hui-Chen; Yo, Yi-Te; Chao, Tai-Kuang; Huang, Hsuan-Cheng; Lin, Ching-Yu; Chu, Tang-Yuan; Lai, Hung-Cheng

2012-01-01

Background Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening. Methods and Findings At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P<0.001). For the detection of cervical intraepithelial neoplasia 3 (CIN3) and worse, the area under the receiver operating characteristic curve (AUC) of ZNF582 was 0.82 (95% confidence interval  = 0.76–0.87). Conclusions Our study shows ZNF582 is frequently methylated in CIN3 and worse lesions, and it is demonstrated as a potential biomarker for the molecular screening of cervical cancer. PMID:22815913

Healthy lifestyle behaviours are positively and independently associated with academic achievement: An analysis of self-reported data from a nationally representative sample of Canadian early adolescents

PubMed Central

Gleddie, Doug; Storey, Kate E.; Davison, Colleen M.; Veugelers, Paul J.

2017-01-01

Introduction The lifestyle behaviours of early adolescents, including diet, physical activity, sleep, and screen usage, are well established contributors to health. These behaviours have also been shown to be associated with academic achievement. Poor academic achievement can additionally contribute to poorer health over the lifespan. This study aims to characterize the associations between health behaviours and self-reported academic achievement. Methods Data from the 2014 Canadian Health Behaviour in School-Aged Children Study (n = 28,608, ages 11–15) were analyzed. Students provided self-report of academic achievement, diet, physical activity, sleep duration, recreational screen time usage, height, weight, and socioeconomic status. Multi-level logistic regression was used to assess the relationship of lifestyle behaviours and body weight status with academic achievement while considering sex, age, and socioeconomic status as potential confounders. Results All health behaviours exhibited independent associations with academic achievement. Frequent consumption of vegetables and fruits, breakfast and dinner with family and regular physical activity were positively associated with higher levels of academic achievement, while frequent consumption of junk food, not meeting sleep recommendations, and overweight and obesity were negatively associated with high academic achievement. Conclusions The present findings demonstrate that lifestyle behaviours are associated with academic achievement, potentially identifying these lifestyle behaviours as effective targets to improve academic achievement in early adolescents. These findings also justify investments in school-based health promotion initiatives. PMID:28753617

Importance of early nutritional screening in patients with gastric cancer.

PubMed

Gavazzi, Cecilia; Colatruglio, Silvia; Sironi, Alessandro; Mazzaferro, Vincenzo; Miceli, Rosalba

2011-12-01

In the present study, we evaluated the relationship between nutritional status, disease stage and quality of life (QoL) in 100 patients recently diagnosed with gastric carcinoma. The patients' nutritional status was investigated with anthropometric, biochemical, inflammatory and functional variables; and we also evaluated the nutritional risk with the Nutritional Risk Screening 2002. Oncological staging was standard. QoL was evaluated using the Functional Assessment of Anorexia/Cachexia Therapy questionnaire. The statistical correlation between nutritional risk score (NRS) and oncological characteristics or QoL was evaluated using both univariable and multivariable analyses. Weight loss and reduction of food intake were the most frequent pathological nutritional indicators, while biochemical, inflammatory and functional variables were in the normal range. According to NRS, thirty-six patients were malnourished or at risk for malnutrition. Patients with NRS ≥ 3 presented a significantly greater percentage of stage IV gastric cancer and pathological values of C-reactive protein, while no correlation was found with the site of tumour. NRS was negatively associated with QoL (P < 0·001) and this relation was independent from oncological and inflammatory variables as confirmed by multivariable analysis. In the present study, we found that in patients with gastric cancer malnutrition is frequent at diagnosis and this is likely due to reduction in food intake. Moreover, NRS is directly correlated with tumour stage and inversely correlated with QoL, which makes it a useful tool to identify patients in need of an early nutritional intervention during oncological treatments.

Health profile and disease determinants among asylum seekers: a cross-sectional retrospective study from an Italian reception centre.

PubMed

Russo, Gianluca; Vita, Serena; Miglietta, Alessandro; Terrazzini, Nadia; Sannella, Alessandra; Vullo, Vincenzo

2016-06-01

Data on diseases' determinants and health status of asylum seekers (ASs) are limited. We performed a cross-sectional retrospective study in a large ASs centre in Italy. Data were collected during a 1-year period. Descriptive statistics were calculated. A χ(2) test was used to assess the association between socio-demographics characteristics of ASs and screening test results. A multiple logistic regression analysis was performed to identify diseases' predictors by using ICD-10 diagnoses classification as outcome variable, socio-demographic characteristics as independent variable and visits' number as confounding variable. Overall, data on 792 ASs (mean age 27 years, 80% males, 58% from Africa) were assessed, 43% underwent voluntary infectious diseases screening and 2843 diagnoses were recorded. The most frequent diagnoses were: respiratory diseases, symptoms/signs not elsewhere classified, digestive diseases and infectious diseases. Gender was the most frequent predictor of ICD-10 diagnoses, while African origin, civil status and education were, respectively, predictive of cardiovascular and infectious diseases, genitourinary diseases and pregnancy-related disorders. Higher mean age was associated with syphilis, HIV and HCV infection and African origin with HIV infection. Communicable diseases were not prevalent in the ASs population we analysed. A stronger cultural mediation support is needed to facilitate prevention, access and continuity of care for ASs. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Healthy lifestyle behaviours are positively and independently associated with academic achievement: An analysis of self-reported data from a nationally representative sample of Canadian early adolescents.

PubMed

Faught, Erin L; Gleddie, Doug; Storey, Kate E; Davison, Colleen M; Veugelers, Paul J

2017-01-01

The lifestyle behaviours of early adolescents, including diet, physical activity, sleep, and screen usage, are well established contributors to health. These behaviours have also been shown to be associated with academic achievement. Poor academic achievement can additionally contribute to poorer health over the lifespan. This study aims to characterize the associations between health behaviours and self-reported academic achievement. Data from the 2014 Canadian Health Behaviour in School-Aged Children Study (n = 28,608, ages 11-15) were analyzed. Students provided self-report of academic achievement, diet, physical activity, sleep duration, recreational screen time usage, height, weight, and socioeconomic status. Multi-level logistic regression was used to assess the relationship of lifestyle behaviours and body weight status with academic achievement while considering sex, age, and socioeconomic status as potential confounders. All health behaviours exhibited independent associations with academic achievement. Frequent consumption of vegetables and fruits, breakfast and dinner with family and regular physical activity were positively associated with higher levels of academic achievement, while frequent consumption of junk food, not meeting sleep recommendations, and overweight and obesity were negatively associated with high academic achievement. The present findings demonstrate that lifestyle behaviours are associated with academic achievement, potentially identifying these lifestyle behaviours as effective targets to improve academic achievement in early adolescents. These findings also justify investments in school-based health promotion initiatives.

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

PubMed Central

Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

2009-01-01

Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

Asymptomatic Bacteriuria and Bacterial Interference.

PubMed

Nicolle, Lindsay E

2015-10-01

Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from <1% in newborns to 10% to 20% of women age 80 years, but is uncommon in men until after age 50 years. Individuals with underlying genitourinary abnormalities, including indwelling devices, may also have a high frequency of asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term-care facilities, from 25% to 50% of women and 15% to 40% of men. Escherichia coli is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients.

Dysphagia risk assessment in acute left-hemispheric middle cerebral artery stroke.

PubMed

Somasundaram, Sriramya; Henke, Christian; Neumann-Haefelin, Tobias; Isenmann, Stefan; Hattingen, Elke; Lorenz, Matthias W; Singer, Oliver C

2014-01-01

Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (<72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control. © 2014 S. Karger AG, Basel.

RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

PubMed

Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

2010-08-18

Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

Healthcare-seeking behaviour in relation to sexual and reproductive health among Thai-born women in Sweden: a qualitative study.

PubMed

Åkerman, Eva; Essén, Birgitta; Westerling, Ragnar; Larsson, Elin

2017-02-01

Thailand is one of the most common countries of origin among immigrants in Sweden and Thai immigrants comprise the immigrant group most frequently diagnosed with HIV. Little is known about their healthcare-seeking behaviour and views on HIV prevention. This study explored Thai women's healthcare-seeking behaviour in relation to sexual and reproductive health and their views on HIV prevention. Nineteen in-depth interviews were conducted with Thai-born women in the Stockholm area. Three themes were identified: (1) poor access to healthcare in Sweden, preferring to seek care in Thailand; (2) partners playing a key role in women's access to healthcare; (3) no perceived risk of HIV, but a positive attitude towards prevention. Despite expressing sexual and reproductive healthcare needs, most women had not sought this type of care, except for the cervical cancer screening programme to which they had been invited. Identified barriers for poor access to healthcare were lack of knowledge about the healthcare system and language difficulties. To achieve 'healthcare on equal terms', programmes and interventions must meet Thai women's healthcare needs and consider what factors influence their care-seeking behaviour. Integrating HIV prevention and contraceptive counselling into the cervical screening programme might be one way to improve access.

Barriers to timely diagnosis and treatment for children with hearing impairment in a southern Indian city: a qualitative study of parents and clinic staff.

PubMed

Merugumala, Sri Vamshi; Pothula, Vijay; Cooper, Max

2017-10-01

In low income countries, deaf children are identified late due to the absence of a universal screening. Hearing impairment is a common yet neglected disability in India that leads to loss of speech and language. This qualitative study explored barriers to accessing appropriate hearing services in one city in southern India. To identify the barriers in timely management of deafness, 25 semi-structured interviews were conducted. Data were examined using Applied Thematic Analysis. Seventeen mothers of deaf children, primarily from low socioeconomic backgrounds, and eight staff members at a charitable hearing centre in Hyderabad. Barriers to accessing hearing services included failure to recognise deafness, the dominant role of elders in household decisions, belief that deafness would resolve, reassurance from a child's overall good health, lack of funds and transportation barriers to reach the centre particularly from rural areas. Parents frequently learned about services through word of mouth. The challenges to accessing appropriate services for deafness operate prior to presentation and include educational, cultural, navigational and financial barriers especially for those of lower socioeconomic status and residents of rural areas. The findings highlighted the need to raise awareness and implement wider screening programmes for early interventions.

Imaging screening of catastrophic neurological events using a software tool: preliminary results.

PubMed

Fernandes, A P; Gomes, A; Veiga, J; Ermida, D; Vardasca, T

2015-05-01

In Portugal, as in most countries, the most frequent organ donors are brain-dead donors. To answer the increasing need for transplants, donation programs have been implemented. The goal is to recognize virtually all the possible and potential brain-dead donors admitted to hospitals. The aim of this work was to describe preliminary results of a software application designed to identify devastating neurological injury victims who may progress to brain death and can be possible organ donors. This was an observational, longitudinal study with retrospective data collection. The software application is an automatic algorithm based on natural language processing for selected keywords/expressions present in the cranio-encephalic computerized tomography (CE CT) scan reports to identify catastrophic neurological situations, with e-mail notification to the Transplant Coordinator (TC). The first 7 months of this application were analyzed and compared with the standard clinical evaluation methodology. The imaging identification tool showed a sensitivity of 77% and a specificity of 66%; predictive positive value (PPV) was 0.8 and predictive negative value (PNV) was 0.7 for the identification of catastrophic neurological events. The methodology proposed in this work seems promising in improving the screening efficiency of critical neurological events. Copyright © 2015 Elsevier Inc. All rights reserved.

Effective screening programmes for cervical cancer in low- and middle-income developing countries.

PubMed

Sankaranarayanan, R; Budukh, A M; Rajkumar, R

2001-01-01

Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives.

Effective screening programmes for cervical cancer in low- and middle-income developing countries.

PubMed Central

Sankaranarayanan, R.; Budukh, A. M.; Rajkumar, R.

2001-01-01

Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives. PMID:11693978

Sparse whole genome sequencing identifies two loci for major depressive disorder

PubMed Central

2015-01-01

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide1, poses a major challenge to genetic analysis. To date no robustly replicated genetic loci have been identified 2, despite analysis of more than 9,000 cases3. Using low coverage genome sequence of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P-value = 2.53×10−10) the other in an intron of the LHPP gene (P = 6.45×10−12). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness. PMID:26176920

Utility of the PHQ-9 to identify major depressive disorder in adult patients in Spanish primary care centres.

PubMed

Muñoz-Navarro, Roger; Cano-Vindel, Antonio; Medrano, Leonardo Adrián; Schmitz, Florian; Ruiz-Rodríguez, Paloma; Abellán-Maeso, Carmen; Font-Payeras, Maria Antonia; Hermosilla-Pasamar, Ana María

2017-08-09

The prevalence of major depressive disorder (MDD) in Spanish primary care (PC) centres is high. However, MDD is frequently underdiagnosed and consequently only some patients receive the appropriate treatment. The present study aims to determine the utility of the Patient Health Questionnaire-9 (PHQ-9) to identify MDD in a subset of PC patients participating in the large PsicAP study. A total of 178 patients completed the full PHQ test, including the depression module (PHQ-9). Also, a Spanish version of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was implemented by clinical psychologists that were blinded to the PHQ-9 results. We evaluated the psychometric properties of the PHQ-9 as a screening tool as compared to the SCID-I as a reference standard. The psychometric properties of the PHQ-9 for a cut-off value of 10 points were as follows: sensitivity, 0.95; specificity, 0.67. Using a cut-off of 12 points, the values were: sensitivity, 0.84; specificity, 0.78. Finally, using the diagnostic algorithm for depression (DSM-IV criteria), the sensitivity was 0.88 and the specificity 0.80. As a screening instrument, the PHQ-9 performed better with a cut-off value of 12 versus the standard cut-off of 10. However, the best psychometric properties were obtained with the DSM-IV diagnostic algorithm for depression. These findings indicate that the PHQ-9 is a highly satisfactory tool that can be used for screening MDD in the PC setting. Current Controlled Trials ISRCTN58437086 . Registered 20 May 2013.

ARID1B is a specific vulnerability in ARID1A-mutant cancers.

PubMed

Helming, Katherine C; Wang, Xiaofeng; Wilson, Boris G; Vazquez, Francisca; Haswell, Jeffrey R; Manchester, Haley E; Kim, Youngha; Kryukov, Gregory V; Ghandi, Mahmoud; Aguirre, Andrew J; Jagani, Zainab; Wang, Zhong; Garraway, Levi A; Hahn, William C; Roberts, Charles W M

2014-03-01

Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.

Screening of extremotolerant fungi for the bioremediation of hydrocarbon contaminated sites

NASA Astrophysics Data System (ADS)

Poyntner, Caroline; Blasi, Barbara; Prenafeta, Francesc; Sterflinger, Katja

2015-04-01

Bioremediation can be used to treat contaminated sites, by taking advantage of microorganisms which have the potential to degrade a wide range of contaminants. While research has been focused mainly on bacteria, the knowledge on other microorganisms, especially fungal communities, is still limited. However, the use of fungi may have advantages compared to bacteria. Extremophile fungi like the black yeasts can withstand high levels of environmental stress (e.g. range of pH, water availability and temperature, presence of toxic chemicals). Therefore they might be applicable in situations, where bacterial communities show limited performance. In order to identify fungi which are good candidates for bioremediation application, a selection of 163 fungal strains, mostly from the group of the black yeasts, was tested for their capability to degrade three different pollutants: hexadecane, toluene, and polychlorinated biphenyl 126, which were used as model compounds for aliphatic hydrocarbons, aromatic hydrocarbons and polychlorinated biphenyls. These chemicals are frequently found in sites contaminated by oil, gas and coal. The screening was based on a two-step selection approach. As a first step, a high throughput method was developed to screen the relatively large amount of fungal strains regarding their tolerance to the contaminants. A microtiter plate based method was developed for monitoring fungal growth in the presence of the selected contaminants photometrically with a Tecan reader. Twenty five strains out of 163, being species of the genera Cladophilaophora, Scedosporium and Exophiala, showed the ability to grow on at least 2 hydrocarbons, and are therefore the most promising candidates for further tests. In a second step, degradation of the contaminants was investigated in more detail for a subset of the screened fungi. This was done by closing the carbon balance in sealed liquid cultures in which the selected pollutant was introduce as the sole source of carbon and energy. Substrate depletion and CO2 accumulation in the headspace were monitored chromatographically. In the course of these experiments, two strains showed a good capacity to grow on toluene. In summary, the presented screening method can be used to identify potential candidates for the fungal degradation of contaminants. Further research is necessary to investigate the potential use of the identified fungal strains for remediation purposes.

RADAR: A novel fast-screening method for reading difficulties with special focus on dyslexia.

PubMed

Smyrnakis, Ioannis; Andreadakis, Vassilios; Selimis, Vassilios; Kalaitzakis, Michail; Bachourou, Theodora; Kaloutsakis, Georgios; Kymionis, George D; Smirnakis, Stelios; Aslanides, Ioannis M

2017-01-01

Dyslexia is a developmental learning disorder of single word reading accuracy and/or fluency, with compelling research directed towards understanding the contributions of the visual system. While dyslexia is not an oculomotor disease, readers with dyslexia have shown different eye movements than typically developing students during text reading. Readers with dyslexia exhibit longer and more frequent fixations, shorter saccade lengths, more backward refixations than typical readers. Furthermore, readers with dyslexia are known to have difficulty in reading long words, lower skipping rate of short words, and high gaze duration on many words. It is an open question whether it is possible to harness these distinctive oculomotor scanning patterns observed during reading in order to develop a screening tool that can reliably identify struggling readers, who may be candidates for dyslexia. Here, we introduce a novel, fast, objective, non-invasive method, named Rapid Assessment of Difficulties and Abnormalities in Reading (RADAR) that screens for features associated with the aberrant visual scanning of reading text seen in dyslexia. Eye tracking parameter measurements that are stable under retest and have high discriminative power, as indicated by their ROC (receiver operating characteristic) curves, were obtained during silent text reading. These parameters were combined to derive a total reading score (TRS) that can reliably separate readers with dyslexia from typical readers. We tested TRS in a group of school-age children ranging from 8.5 to 12.5 years of age. TRS achieved 94.2% correct classification of children tested. Specifically, 35 out of 37 control (specificity 94.6%) and 30 out of 32 readers with dyslexia (sensitivity 93.8%) were classified correctly using RADAR, under a circular validation condition (see section Results/Total Reading Score) where the individual evaluated was not included in the test construction group. In conclusion, RADAR is a novel, automated, fast and reliable way to identify children at high risk of dyslexia that is amenable to large-scale screening. Moreover, analysis of eye movement parameters obtained with RADAR during reading will likely be useful for implementing individualized treatment strategies and for monitoring objectively the success of chosen interventions. We envision that it will be possible to use RADAR as a sensitive, objective, and quantitative first pass screen to identify individuals with reading disorders that manifest with abnormal oculomotor reading strategies, like dyslexia.

RADAR: A novel fast-screening method for reading difficulties with special focus on dyslexia

PubMed Central

Smyrnakis, Ioannis; Andreadakis, Vassilios; Selimis, Vassilios; Kalaitzakis, Michail; Bachourou, Theodora; Kaloutsakis, Georgios; Kymionis, George D.; Smirnakis, Stelios; Aslanides, Ioannis M.

2017-01-01

Dyslexia is a developmental learning disorder of single word reading accuracy and/or fluency, with compelling research directed towards understanding the contributions of the visual system. While dyslexia is not an oculomotor disease, readers with dyslexia have shown different eye movements than typically developing students during text reading. Readers with dyslexia exhibit longer and more frequent fixations, shorter saccade lengths, more backward refixations than typical readers. Furthermore, readers with dyslexia are known to have difficulty in reading long words, lower skipping rate of short words, and high gaze duration on many words. It is an open question whether it is possible to harness these distinctive oculomotor scanning patterns observed during reading in order to develop a screening tool that can reliably identify struggling readers, who may be candidates for dyslexia. Here, we introduce a novel, fast, objective, non-invasive method, named Rapid Assessment of Difficulties and Abnormalities in Reading (RADAR) that screens for features associated with the aberrant visual scanning of reading text seen in dyslexia. Eye tracking parameter measurements that are stable under retest and have high discriminative power, as indicated by their ROC (receiver operating characteristic) curves, were obtained during silent text reading. These parameters were combined to derive a total reading score (TRS) that can reliably separate readers with dyslexia from typical readers. We tested TRS in a group of school-age children ranging from 8.5 to 12.5 years of age. TRS achieved 94.2% correct classification of children tested. Specifically, 35 out of 37 control (specificity 94.6%) and 30 out of 32 readers with dyslexia (sensitivity 93.8%) were classified correctly using RADAR, under a circular validation condition (see section Results/Total Reading Score) where the individual evaluated was not included in the test construction group. In conclusion, RADAR is a novel, automated, fast and reliable way to identify children at high risk of dyslexia that is amenable to large-scale screening. Moreover, analysis of eye movement parameters obtained with RADAR during reading will likely be useful for implementing individualized treatment strategies and for monitoring objectively the success of chosen interventions. We envision that it will be possible to use RADAR as a sensitive, objective, and quantitative first pass screen to identify individuals with reading disorders that manifest with abnormal oculomotor reading strategies, like dyslexia. PMID:28800632

Epidemiology and Genetic Characterization of Hepatitis A Virus Genotype IIA▿

PubMed Central

Desbois, Delphine; Couturier, Elisabeth; Mackiewicz, Vincent; Graube, Arielle; Letort, Marie-José; Dussaix, Elisabeth; Roque-Afonso, Anne-Marie

2010-01-01

Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5′ untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored. PMID:20592136

Risk assessment of water quality in three North Carolina, USA, streams supporting federally endangered freshwater mussels (Unionidae)

USGS Publications Warehouse

Ward, S.; Augspurger, T.; Dwyer, F.J.; Kane, C.; Ingersoll, C.G.

2007-01-01

Water quality data were collected from three drainages supporting the endangered Carolina heelsplitter (Lasmigona decorata) and dwarf wedgemussel (Alasmidonta heterodon) to determine the potential for impaired water quality to limit the recovery of these freshwater mussels in North Carolina, USA. Total recoverable copper, total residual chlorine, and total ammonia nitrogen were measured every two months for approximately a year at sites bracketing wastewater sources and mussel habitat. These data and state monitoring datasets were compared with ecological screening values, including estimates of chemical concentrations likely to be protective of mussels, and federal ambient water quality criteria to assess site risks following a hazard quotient approach. In one drainage, the site-specific ammonia ecological screening value for acute exposures was exceeded in 6% of the samples, and 15% of samples exceeded the chronic ecological screening value; however, ammonia concentrations were generally below levels of concern in other drainages. In all drainages, copper concentrations were higher than ecological screening values most frequently (exceeding the ecological screening values for acute exposures in 65-94% of the samples). Chlorine concentrations exceeding the acute water quality criterion were observed in 14 and 35% of samples in two of three drainages. The ecological screening values were exceeded most frequently in Goose Creek and the Upper Tar River drainages; concentrations rarely exceeded ecological screening values in the Swift Creek drainage except for copper. The site-specific risk assessment approach provides valuable information (including site-specific risk estimates and ecological screening values for protection) that can be applied through regulatory and nonregulatory means to improve water quality for mussels where risks are indicated and pollutant threats persist. ?? 2007 SETAC.

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

PubMed Central

Carmody, J Bryan; Norwood, Victoria F

2013-01-01

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

Skills and offensive tactics used in pick-up basketball games.

PubMed

Wang, Jianyu; Liu, Wenhao; Moffit, Jeffrey

2009-10-01

The purpose of this study was to describe skills and offensive tactics frequently used in pick-up basketball games. 65 participants were recruited from public basketball courts. An observational instrument was developed to analyze the performances of pick-up games. Participants' performances were videotaped and coded. Results indicated that the passing skills most frequently observed in the games were chest pass, overhead pass, and bounce pass. For dribbling, crossover dribble and change-of-pace dribble were frequently observed. Jump shot, set shot, and layup were also frequently used. The offensive tactics frequently used included drive, cut, and set screen. The study may be beneficial for helping young people prepare to play pick-up basketball games.

Identification and classification of genes required for tolerance to freeze-thaw stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains.

PubMed

Ando, Akira; Nakamura, Toshihide; Murata, Yoshinori; Takagi, Hiroshi; Shima, Jun

2007-03-01

Yeasts used in bread making are exposed to freeze-thaw stress during frozen-dough baking. To clarify the genes required for freeze-thaw tolerance, genome-wide screening was performed using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 58 gene deletions that conferred freeze-thaw sensitivity. These genes were then classified based on their cellular function and on the localization of their products. The results showed that the genes required for freeze-thaw tolerance were frequently involved in vacuole functions and cell wall biogenesis. The highest numbers of gene products were components of vacuolar H(+)-ATPase. Next, the cross-sensitivity of the freeze-thaw-sensitive mutants to oxidative stress and to cell wall stress was studied; both of these are environmental stresses closely related to freeze-thaw stress. The results showed that defects in the functions of vacuolar H(+)-ATPase conferred sensitivity to oxidative stress and to cell wall stress. In contrast, defects in gene products involved in cell wall assembly conferred sensitivity to cell wall stress but not to oxidative stress. Our results suggest the presence of at least two different mechanisms of freeze-thaw injury: oxidative stress generated during the freeze-thaw process, and defects in cell wall assembly.

Occult cancer detection in patients with hemostatic disorder and venous thromboembolism.

PubMed

Husseinzadeh, Holleh; Carrier, Marc

2018-03-01

There are physiologic ties between Von Willebrand Factor (VWF) and circulating tumor cells. VWF appears to play a role in tumor biology, but it is unclear whether cancer behavior differs in Von Willebrand Disease. In patients presenting with venous thromboembolism (VTE), occult cancer is frequently considered as an underlying cause. The prevalence of occult cancer after provoked VTE is low (3%); therefore, cancer screening in these patients is not routinely recommended. In those with unprovoked VTE, occult cancer is more prevalent, estimated between 4 and 10%. Due to this elevated risk, occult cancer screening is recommended in this population. Multiple studies have investigated whether a "limited" approach (including history and physical exam, basic labs, and chest X-ray) versus "extensive" approach (addition of advanced imaging, such as computer tomography) is more effective. Current data fails to demonstrate extensive screening strategies diagnose more occult cancer, miss fewer cancers during follow up, or improve cancer-related mortality. Furthermore, many patients may be needlessly exposed to unnecessary diagnostic procedures with their associated complications and costs, as well as significant anxiety. Therefore, the decision to perform additional testing should be made on a case-by-case basis. Additional studies are needed to identify subgroups of patients with unprovoked VTE at highest risk for occult cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parents' interest in whole-genome sequencing of newborns.

PubMed

Goldenberg, Aaron J; Dodson, Daniel S; Davis, Matthew M; Tarini, Beth A

2014-01-01

The aim of this study was to assess parents' interest in whole-genome sequencing for newborns. We conducted a survey of a nationally representative sample of 1,539 parents about their interest in whole-genome sequencing of newborns. Participants were randomly presented with one of two scenarios that differed in the venue of testing: one offered whole-genome sequencing through a state newborn screening program, whereas the other offered whole-genome sequencing in a pediatrician's office. Overall interest in having future newborns undergo whole-genome sequencing was generally high among parents. If whole-genome sequencing were offered through a state's newborn-screening program, 74% of parents were either definitely or somewhat interested in utilizing this technology. If offered in a pediatrician's office, 70% of parents were either definitely or somewhat interested. Parents in both groups most frequently identified test accuracy and the ability to prevent a child from developing a disease as "very important" in making a decision to have a newborn's whole genome sequenced. These data may help health departments and children's health-care providers anticipate parents' level of interest in genomic screening for newborns. As whole-genome sequencing is integrated into clinical and public health services, these findings may inform the development of educational strategies and outreach messages for parents.

Mutational analysis of GALT gene in Greek patients with galactosaemia: identification of two novel mutations and clinical evaluation.

PubMed

Schulpis, Kleopatra H; Thodi, Georgia; Iakovou, Konstantinos; Chatzidaki, Maria; Dotsikas, Yannis; Molou, Elina; Triantafylli, Olga; Loukas, Yannis L

2017-10-01

Classical galactosaemia is an inborn error of metabolism due to the deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). The aim of the study was to identify the underlying mutations in Greek patients with GALT deficiency and evaluate their psychomotor and speech development. Patients with GALT deficiency (n = 17) were picked up through neonatal screening. Mutational analysis was conducted via Sanger sequencing, while in silico analysis was used in the cases of novel missense mutations. Psychomotor speech development tests were utilized for the clinical evaluation of the patients. Eleven different mutations in the GALT gene were detected in the patient cohort, including two novel ones. The most frequent mutation was p.Q188R (c.563 A > G). As for the novel mutations, p.M298I (c.894 G > A) was identified in four out of 32 independent alleles, while p.P115S (c.343 C > T) was identified once. Psychomotor evaluation revealed that most of the patients were found in the borderline area (Peabody test), while only two had speech delay problems. The WISK test revealed three patients at borderline limits and two were at lower than normal limits. The mutational spectrum of the GALT gene in Greek patients is presented for the first time. The mutation p.Q188R is the most frequent among Greek patients. Two novel mutations were identified and their potential pathogenicity was estimated. Regarding the phenotypic characteristics, psychomotor disturbances and speech delay were mainly observed among GALT-deficient patients.

Predicting plant attractiveness to pollinators with passive crowdsourcing.

PubMed

Bahlai, Christie A; Landis, Douglas A

2016-06-01

Global concern regarding pollinator decline has intensified interest in enhancing pollinator resources in managed landscapes. These efforts frequently emphasize restoration or planting of flowering plants to provide pollen and nectar resources that are highly attractive to the desired pollinators. However, determining exactly which plant species should be used to enhance a landscape is difficult. Empirical screening of plants for such purposes is logistically daunting, but could be streamlined by crowdsourcing data to create lists of plants most probable to attract the desired pollinator taxa. People frequently photograph plants in bloom and the Internet has become a vast repository of such images. A proportion of these images also capture floral visitation by arthropods. Here, we test the hypothesis that the abundance of floral images containing identifiable pollinator and other beneficial insects is positively associated with the observed attractiveness of the same species in controlled field trials from previously published studies. We used Google Image searches to determine the correlation of pollinator visitation captured by photographs on the Internet relative to the attractiveness of the same species in common-garden field trials for 43 plant species. From the first 30 photographs, which successfully identified the plant, we recorded the number of Apis (managed honeybees), non-Apis (exclusively wild bees) and the number of bee-mimicking syrphid flies. We used these observations from search hits as well as bloom period (BP) as predictor variables in Generalized Linear Models (GLMs) for field-observed abundances of each of these groups. We found that non-Apis bees observed in controlled field trials were positively associated with observations of these taxa in Google Image searches (pseudo-R (2) of 0.668). Syrphid fly observations in the field were also associated with the frequency they were observed in images, but this relationship was weak. Apis bee observations were not associated with Internet images, but were slightly associated with BP. Our results suggest that passively crowdsourced image data can potentially be a useful screening tool to identify candidate plants for pollinator habitat restoration efforts directed at wild bee conservation. Increasing our understanding of the attractiveness of a greater diversity of plants increases the potential for more rapid and efficient research in creating pollinator-supportive landscapes.

Analysis of risk factors in the development of retinopathy of prematurity.

PubMed

Knezević, Sanja; Stojanović, Nadezda; Oros, Ana; Savić, Dragana; Simović, Aleksandra; Knezević, Jasmina

2011-01-01

Retinopathy of prematurity (ROP) is a multifactorial disease that occurs most frequently in very small and very sick preterm infants, and it has been identified as the major cause of childhood blindness. The aim of this study was to evaluate ROP incidence and risk factors associated with varying degrees of illness. The study was conducted at the Centre for Neonatology, Paediatric Clinic of the Clinical Centre Kragujevac, Serbia, in the period from June 2006 to December 2008. Ophthalmologic screening was performed in all children with body weight lower than 2000 g or gestational age lower than 36 weeks. We analyzed eighteen postnatal and six perinatal risk factors and the group correlations for each of the risk factors. Out of 317 children that were screened, 56 (17.7%) developed a mild form of ROP, while 68 (21.5%) developed a severe form. Univariate analysis revealed a large number of statistically significant risk factors for the development of ROP, especially the severe form. Multivariate logistical analysis further separated two independent risk factors: small birth weight (p = 0.001) and damage of central nervous system (p = 0.01). Independent risk factors for transition from mild to severe forms of ROP were identified as: small birth weight (p = 0.05) and perinatal risk factors (p = 0.02). Small birth weight and central nervous system damage were risk factors for the development of ROP, perinatal risk factors were identified as significant for transition from mild to severe form of ROP.

Identification of three novel LRRK2 mutations associated with Parkinson's disease in a Calabrian population.

PubMed

Anfossi, Maria; Colao, Rosanna; Gallo, Maura; Bernardi, Livia; Conidi, M Elena; Frangipane, Francesca; Vasso, Franca; Puccio, Gianfranco; Clodomiro, Alessandra; Mirabelli, Maria; Curcio, Sabrina A M; Torchia, Giusi; Smirne, Nicoletta; Di Lorenzo, Raffaele; Maletta, Raffaele; Bruni, Amalia C

2014-01-01

LRRK2 mutations are common in familial and sporadic Parkinson's disease (PD) cases. We present a screening of the most frequently mutated exons of LRRK2 in Calabrian population. Eighty-eight PD patients diagnosed according to standard criteria, underwent screening for LRRK2 mutations in exons 19, 21, 24, 25, 27, 29, 31, 32, 33, 35, 38, 40, 41, and 48. Eight LRRK2 variations were identified in nine patients affected by PD, including three novel missense variations (p.Phe1227Leu, p.Gly1520Ala, p.Ile2020Ser) and five previously identified mutations (p.Ala1151Thr, IVS31+3A>G, p.Arg1514Gln, p.Gly2019Ser, p.Thr2356Ile). LRRK2 frequency mutations were approximately 10.2% in all PD patients, 12% in familial, 8% in sporadic cases. The p.Gly2019Ser mutation was found in 2.3% of the total cohort and in 3.2% of sporadic cases. The clinical features of LRRK2-associated with PD in our patients were similar to those of idiopathic PD although most LRRK2 mutated patients presented with bradykinesia instead of tremor; 33.3% developed dementia. We identified three novel LRRK2 mutations and reported a higher frequency in Calabria compared to previously reported data possibly due to the relative genetic isolation of the Calabrian population. These findings contribute to the understanding of the role of LRKK2 variations in PD and provide additional genetic insight into this disease.

Extended Follow-Up Frequently Asked Questions | Division of Cancer Prevention

Cancer.gov

1. What is the PLCO Central Data Coordinating Center?The PLCO Central Data Coordinating Center (CDCC) is an extension of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The extension will be coordinated by one site under the direction of the National Cancer Institute (NCI) rather than ten PLCO Screening Centers to reduce costs. Westat which has served

Impact of asian ethnicity on colorectal cancer screening: a population-based analysis.

PubMed

Homayoon, Babak; Shahidi, Neal C; Cheung, Winson Y

2013-04-01

Although research shows that African Americans and Hispanics frequently receive less colorectal cancer screening (CRCS) than whites, few studies have focused on CRCS among Asians. The aims of this study were to compare CRCS between Asians and whites and to evaluate for clinical predictors of CRCS. From the 2007 California Health Interview Survey, we identified all Asian and white respondents who were eligible for CRCS. Logistic regression was performed to evaluate for differences in CRCS. We used stratified and interaction analyses to examine whether associations between race and CRCS were modified by insurance status, birthplace, or language skills, while controlling for other confounders. Baseline characteristics were similar between Asians and whites. Only 58% of Asians and 66% of whites reported undergoing up-to-date CRCS (P < 0.01). In multivariate analyses, visiting a physician more than 5 times produced the highest odds of being up-to-date with screening. When compared with whites, Asians had decreased odds of being up-to-date with screening. Stratified analyses showed that this disparity existed mainly in the insured, but not in the uninsured, and it was not modified by place of birth or English language proficiency. Despite its ability to reduce mortality, CRCS is suboptimal in our US population-based cohort of Asians when compared with whites. A contributing factor to this problem for the Chinese and Koreans may be a lack of awareness regarding CRCS, whereas the source of the problem in the Vietnamese seems to be related to healthcare access.

Cancer incidence and mortality rates in Bermuda.

PubMed

Dallaire, F; Dewailly, E; Rouja, P

2009-09-01

To describe cancer and mortality rates in Bermuda and to compare such rates to those of the United States of America (U.S.A.). Age-adjusted race-specific cancer incidence rates for Bermuda were calculated using the Bermuda Cancer Registry. These rates were then compared to U.S.A. cancer rates published by the National Cancer Institute. Overall age-adjusted incidence rate was 495 cases per 100,000 for Blacks and 527 cases per 100,000 for Whites. Incident cases were more frequent among men than women in both races. For Blacks, the highest incidences were prostate for men and breast for women, followed by colon/rectum and lung cancer. For Whites, if we exclude benign skin cancers, the picture was similar with the notable exception of lung cancer being more frequent than colon/rectum in White males. When Bermuda's rates were compared to those of the U.S.A., overall cancer rates were similar in both countries. Rates in Bermuda were higher for cancer of the mouth, ovarian cancer (Black women), melanoma (Whites), colorectal cancer (White women) and breast cancer (White women). Lung and colorectal cancers were less frequent in Bermuda's Black population. Further epidemiological studies are needed to identify potential risk factors that could contribute to these differences. Screening and prevention strategies could be adjusted accordingly.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia

PubMed Central

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; LaRochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A.; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean

2013-01-01

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reported GATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. PMID:23223431

The diagnosis of cystic fibrosis.

PubMed

De Boeck, Kris; Vermeulen, Francois; Dupont, Lieven

2017-06-01

Establishing the diagnosis of cystic fibrosis (CF) is straight forward in the majority of patients: they present with a clear clinical picture (most frequently chronic respiratory symptoms plus malabsorption), the sweat chloride value is>60mmol/L and two known disease causing CFTR mutations are identified. In less than 5% of subjects, mainly those with a milder or limited phenotype, the diagnostic process is more complex, because initial diagnostic test results are inconclusive: sweat chloride concentration in the intermediate range, less than 2 CF causing mutations identified or both. These patients should be referred to expert centers where bioassays of CFTR function like nasal potential difference measurement or intestinal current measurement can be done. Still, in some patients, despite symptoms compatible with CF and some indication of CFTR dysfunction (e.g. only intermediate sweat chloride value), diagnostic criteria are not met (e.g. only 1 CFTR mutation identified). For these subjects, the term CFTR related disorder (CFTR-RD) is used. Patients with disseminated bronchiectasis, congenital bilateral absence of the vas deferens and acute or recurrent pancreatitis may fall in this category. CF has a very wide disease spectrum and increasingly the diagnosis is being made during adult life, mainly in subjects with milder phenotypes. In many countries, nationwide CF newborn screening (NBS) has been introduced. In screen positive babies, the diagnosis of CF must be confirmed by a sweat test demonstrating a sweat chloride concentration above 60mmol/L. To achieve the benefit of NBS, every baby in whom the diagnosis of CF is confirmed must receive immediate follow-up and treatment in a CF reference center. CF NBS is not full proof: some diagnoses will be missed and in some babies the diagnosis cannot be confirmed nor ruled out with certainty. Screening algorithms that include gene sequencing will detect a high number of such babies that are screen positive with an inconclusive diagnosis (CFSPID). Even in 2016, the most reliable and widely available diagnostic test for CF is the measurement of chloride concentration in sweat. The method of choice is sweat induction by pilocarpine iontophoresis, followed by sweat collection on a gauze or filter paper or in a Macroduct coil. Since mutation specific therapies have become available, it is important to identify the mutations responsible for CF in each individual patient. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Murine models of osteosarcoma: A piece of the translational puzzle.

PubMed

Walia, Mannu K; Castillo-Tandazo, Wilson; Mutsaers, Anthony J; Martin, Thomas John; Walkley, Carl R

2018-06-01

Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. While our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targets, in addition to testing the role of additional mutations in vivo. Most recently these models have begun to be used for discovery based approaches and screens, which hold significant promise in furthering our understanding of the genetic and therapeutic sensitivities of OS. In this review, we discuss the mouse models of OS that have been reported in the last 3-5 years and newly identified pathways from these studies. Finally, we discuss the preclinical utilization of the mouse models of OS for identifying and validating actionable targets to improve patient outcome. © 2017 Wiley Periodicals, Inc.

Feature Screening for Ultrahigh Dimensional Categorical Data with Applications.

PubMed

Huang, Danyang; Li, Runze; Wang, Hansheng

2014-01-01

Ultrahigh dimensional data with both categorical responses and categorical covariates are frequently encountered in the analysis of big data, for which feature screening has become an indispensable statistical tool. We propose a Pearson chi-square based feature screening procedure for categorical response with ultrahigh dimensional categorical covariates. The proposed procedure can be directly applied for detection of important interaction effects. We further show that the proposed procedure possesses screening consistency property in the terminology of Fan and Lv (2008). We investigate the finite sample performance of the proposed procedure by Monte Carlo simulation studies, and illustrate the proposed method by two empirical datasets.

Are 2 Questions Enough to Screen for Depression and Anxiety in Patients With Chronic Low Back Pain?

PubMed Central

Lie, Stein Atle; Eriksen, Hege R.

2014-01-01

Study Design. Cross-sectional study. Objective. To examine the sensitivity of 2 single-item questions compared with 2 longer questionnaires for screening depression and anxiety among patients with chronic low back pain (CLBP). Summary of Background Data. Psychosocial factors are frequently identified as risk factors for developing CLBP and as predictors for treatment, and questionnaires are often used to screen for this. Shorter instruments may be easier to use in clinical practice settings. Methods. A total of 564 patients with 2 to 10 months of at least 50% sickness absence due to nonspecific low back pain were assessed for depression and anxiety with the Mini-International Neuropsychiatric Interview (MINI). Single-item questions for depression and anxiety from the Subjective Health Complaint Inventory and 2 longer questionnaires, the Hospital Anxiety and Depression Scale and Hopkins Symptom Checklist–25, were compared with MINI results, considered the “gold standard” in this study. Sensitivity and specificity of single-item and longer questionnaires and receiver operating characteristic curves were compared. Results. According to MINI, the prevalence of anxiety disorders was 12% whereas that of depressive disorders was 4%. The screening questions showed 95% sensitivity and 56% specificity for depressive disorders and 68% sensitivity and 85% specificity for anxiety disorders. The longer questionnaire, Hospital Anxiety and Depression Scale, showed 91% sensitivity and 85% specificity for depressive disorders and 58% sensitivity and 83% specificity for anxiety disorders. Hopkins Symptom Checklist–25 showed 86% sensitivity and 74% specificity for depressive disorders and 67% sensitivity and 87% specificity for anxiety disorders. For 3 of the anxiety disorders and 2 of the depressive disorders, a perfect sensitivity was found between the screening questions and MINI. Conclusions. A single-item screening question was sensitive for depression but less sensitive for anxiety. The screening questions further performed equal to 2 widely used questionnaires. Validation of these results in other populations and compared with other short-item screeners is needed. Level of Evidence: 3 PMID:24480946

Can abstract screening workload be reduced using text mining? User experiences of the tool Rayyan.

PubMed

Olofsson, Hanna; Brolund, Agneta; Hellberg, Christel; Silverstein, Rebecca; Stenström, Karin; Österberg, Marie; Dagerhamn, Jessica

2017-09-01

One time-consuming aspect of conducting systematic reviews is the task of sifting through abstracts to identify relevant studies. One promising approach for reducing this burden uses text mining technology to identify those abstracts that are potentially most relevant for a project, allowing those abstracts to be screened first. To examine the effectiveness of the text mining functionality of the abstract screening tool Rayyan. User experiences were collected. Rayyan was used to screen abstracts for 6 reviews in 2015. After screening 25%, 50%, and 75% of the abstracts, the screeners logged the relevant references identified. A survey was sent to users. After screening half of the search result with Rayyan, 86% to 99% of the references deemed relevant to the study were identified. Of those studies included in the final reports, 96% to 100% were already identified in the first half of the screening process. Users rated Rayyan 4.5 out of 5. The text mining function in Rayyan successfully helped reviewers identify relevant studies early in the screening process. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular screening of 246 Portuguese Aspergillus isolates among different clinical and environmental sources.

PubMed

Sabino, Raquel; Veríssimo, Cristina; Parada, Helena; Brandão, João; Viegas, Carla; Carolino, Elisabete; Clemons, Karl V; Stevens, David A

2014-07-01

Clinical and environmental samples from Portugal were screened for the presence of Aspergillus and the distributions of the species complexes were determined in order to understand how their distributions differ based on their source. Fifty-seven Aspergillus isolates from clinical samples were collected from 10 health institutions. Six species complexes were detected by internal transcribed spacer sequencing; Fumigati, Flavi, and Nigri were found most frequently (50.9%, 21.0%, and 15.8%, respectively). β-tubulin and calmodulin sequencing resulted in seven cryptic species (A. awamorii, A. brasiliensis, A. fructus, A. lentulus, A. sydowii, A. tubingensis, Emericella echinulata) being identified among the 57 isolates. Thirty-nine isolates of Aspergillus were recovered from beach sand and poultry farms, 31 from swine farms, and 80 from hospital environments, for a total 189 isolates. Eleven species complexes were found in these 189 isolates, and those belonging to the Versicolores species complex were found most frequently (23.8%). There was a significant association between the different environmental sources and distribution of the species complexes; the hospital environment had greater variability of species complexes than other environmental locations. A high prevalence of cryptic species within the Circumdati complex was detected in several environments; from the isolates analyzed, at least four cryptic species were identified, most of them growing at 37ºC. Because Aspergillus species complexes have different susceptibilities to antifungals, knowing the species-complex epidemiology for each setting, as well as the identification of cryptic species among the collected clinical isolates, is important. This may allow preventive and corrective measures to be taken, which may result in decreased exposure to those organisms and a better prognosis. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A redox proteomics approach to investigate the mode of action of nanomaterials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riebeling, Christian; Wiemann, Martin; Schnekenburger, Jürgen

2016-05-15

Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye basedmore » read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways. - Highlights: • Oxidative stress is a general paradigm for nanomaterial hazard mechanism of action. • Reactive oxygen species generation can be predicted using acellular assays. • Cellular assays based on fluorescence suffer from interference by nanomaterials. • Protein carbonylation is an irreversible and predictive mark of oxidative stress. • Proteomics of carbonylation indicates affected pathways and mechanism of action.« less

Exploring attitudes and preferences for dementia screening in Britain: contributions from carers and the general public.

PubMed

Martin, Steven; Fleming, Jane; Cullum, Sarah; Dening, Tom; Rait, Greta; Fox, Chris; Katona, Cornelius; Brayne, Carol; Lafortune, Louise

2015-09-09

Dementia is becoming one of the most important emerging public health concerns in a generation. In societal approaches to the mitigation of major disease 'burden', population screening can sometimes provide an effective approach to improving detection of disease and outcomes. However the acceptability of a systematic population screening programme for dementia, to the British public, is not known. A Patient and Public Involvement (PPI) event was organised to give members of the public from the East of England an opportunity to offer their perspectives and to comment on the findings of a systematic literature review looking at attitudes and preferences towards screening for dementia. The event was attended by 36 members of the public and eight national Alzheimer's Society Research Network volunteers. The morning discussion contained a presentation, which defined population screening for attendees but contained no reference to the findings of the review. In the afternoon, findings of the review were presented and a discussion on the results was facilitated. The discussions were recorded, transcribed and subjected to thematic analysis. The NVivo qualitative data software was used to facilitate this process. A total of 23 key themes emerged in relation to the carer and general population. The most frequent themes which emerged were the low levels of understanding and awareness around the dementia syndrome; the acceptability and validity of any tests; costs to the National Health Service (NHS); an individual's existing health status existing health status; financial/profit motive for screening; the inability to change prognosis; and the importance and availability of support. Factors such as personal beliefs, experiences and attitudes to health impact on decisions to be screened for dementia. A number of additional concerns were raised which were not previously identified in the systematic literature review. These were around the economic incentives for screening (profit motive), the provision of social support, and the economic/social impacts of screening programmes. This may reflect cultural differences in health and social care funding models between Britain and other countries where previous research was conducted.

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.

PubMed

Skates, Steven J; Greene, Mark H; Buys, Saundra S; Mai, Phuong L; Brown, Powel; Piedmonte, Marion; Rodriguez, Gustavo; Schorge, John O; Sherman, Mark; Daly, Mary B; Rutherford, Thomas; Brewster, Wendy R; O'Malley, David M; Partridge, Edward; Boggess, John; Drescher, Charles W; Isaacs, Claudine; Berchuck, Andrew; Domchek, Susan; Davidson, Susan A; Edwards, Robert; Elg, Steven A; Wakeley, Katie; Phillips, Kelly-Anne; Armstrong, Deborah; Horowitz, Ira; Fabian, Carol J; Walker, Joan; Sluss, Patrick M; Welch, William; Minasian, Lori; Horick, Nora K; Kasten, Carol H; Nayfield, Susan; Alberts, David; Finkelstein, Dianne M; Lu, Karen H

2017-07-15

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% ( P = 0.0001), and PPV was 4.6% versus 10% ( P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR . ©2017 American Association for Cancer Research.

A reliable computational workflow for the selection of optimal screening libraries.

PubMed

Gilad, Yocheved; Nadassy, Katalin; Senderowitz, Hanoch

2015-01-01

The experimental screening of compound collections is a common starting point in many drug discovery projects. Successes of such screening campaigns critically depend on the quality of the screened library. Many libraries are currently available from different vendors yet the selection of the optimal screening library for a specific project is challenging. We have devised a novel workflow for the rational selection of project-specific screening libraries. The workflow accepts as input a set of virtual candidate libraries and applies the following steps to each library: (1) data curation; (2) assessment of ADME/T profile; (3) assessment of the number of promiscuous binders/frequent HTS hitters; (4) assessment of internal diversity; (5) assessment of similarity to known active compound(s) (optional); (6) assessment of similarity to in-house or otherwise accessible compound collections (optional). For ADME/T profiling, Lipinski's and Veber's rule-based filters were implemented and a new blood brain barrier permeation model was developed and validated (85 and 74 % success rate for training set and test set, respectively). Diversity and similarity descriptors which demonstrated best performances in terms of their ability to select either diverse or focused sets of compounds from three databases (Drug Bank, CMC and CHEMBL) were identified and used for diversity and similarity assessments. The workflow was used to analyze nine common screening libraries available from six vendors. The results of this analysis are reported for each library providing an assessment of its quality. Furthermore, a consensus approach was developed to combine the results of these analyses into a single score for selecting the optimal library under different scenarios. We have devised and tested a new workflow for the rational selection of screening libraries under different scenarios. The current workflow was implemented using the Pipeline Pilot software yet due to the usage of generic components, it can be easily adapted and reproduced by computational groups interested in rational selection of screening libraries. Furthermore, the workflow could be readily modified to include additional components. This workflow has been routinely used in our laboratory for the selection of libraries in multiple projects and consistently selects libraries which are well balanced across multiple parameters.Graphical abstract.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

PubMed Central

2013-01-01

Background Colorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening. Methods/Design A total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC. Discussion This study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC. Trial registration ClinicalTrials.gov Identifier: NCT01651624. PMID:23497601

Improving clinical cognitive testing

PubMed Central

Gale, Seth A.; Barrett, A.M.; Boeve, Bradley F.; Chatterjee, Anjan; Coslett, H. Branch; D'Esposito, Mark; Finney, Glen R.; Gitelman, Darren R.; Hart, John J.; Lerner, Alan J.; Meador, Kimford J.; Pietras, Alison C.; Voeller, Kytja S.; Kaufer, Daniel I.

2015-01-01

Objective: To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. Methods: Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. Results: Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. Conclusions: We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment. PMID:26163433

Audit feedback on reading performance of screening mammograms: An international comparison.

PubMed

Hofvind, S; Bennett, R L; Brisson, J; Lee, W; Pelletier, E; Flugelman, A; Geller, B

2016-09-01

Providing feedback to mammography radiologists and facilities may improve interpretive performance. We conducted a web-based survey to investigate how and why such feedback is undertaken and used in mammographic screening programmes. The survey was sent to representatives in 30 International Cancer Screening Network member countries where mammographic screening is offered. Seventeen programmes in 14 countries responded to the survey. Audit feedback was aimed at readers in 14 programmes, and facilities in 12 programmes. Monitoring quality assurance was the most common purpose of audit feedback. Screening volume, recall rate, and rate of screen-detected cancers were typically reported performance measures. Audit reports were commonly provided annually, but more frequently when target guidelines were not reached. The purpose, target audience, performance measures included, form and frequency of the audit feedback varied amongst mammographic screening programmes. These variations may provide a basis for those developing and improving such programmes. © The Author(s) 2016.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

PubMed

Bale, Abhijith; Pai, C Ganesh; Shetty, Shiran; Balaraju, Girisha; Shetty, Anurag

2018-06-01

Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE ( P  = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B ( P  ≤ 0.001) and C ( P  ≤ 0.001) compared to class A. MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

CAGE, RAPS4, RAPS4-QF and AUDIT Screening Tests for Men and Women Admitted for Acute Alcohol Intoxication to an Emergency Department: Are Standard Thresholds Appropriate?

PubMed Central

Geneste, J.; Pereira, B.; Arnaud, B.; Christol, N.; Liotier, J.; Blanc, O.; Teissedre, F.; Hope, S.; Schwan, R.; Llorca, P.M.; Schmidt, J.; Cherpitel, C.J.; Malet, L.; Brousse, G.

2012-01-01

Aims: A number of screening instruments are routinely used in Emergency Department (ED) situations to identify alcohol-use disorders (AUD). We wished to study the psychometric features, particularly concerning optimal thresholds scores (TSs), of four assessment scales frequently used to screen for abuse and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test (AUDIT) questionnaires, particularly in the sub-group of people admitted for acute alcohol intoxication (AAI). Methods: All included patients [AAI admitted to ED (blood alcohol level ≥0.8 g/l)] were assessed by the four scales, and with a gold standard (alcohol dependence⁄abuse section of the Mini International Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of the scales, we used Youden's index, efficiency, receiver operating characteristic (ROC) curve techniques and quality ROC curve technique for optimized TS (indices of quality). Results: A total of 164 persons (122 males, 42 females) were included in the study. Nineteen (11.60%) were identified as alcohol abusers alone and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically significant difference between men and women (P < 0.05) in performance of the screening tests RAPS4 (≥1) and CAGE (≥2) for detecting abuse. Also, in this population, we show an increase in TSs of RAPS4 (≥2) and CAGE (≥3) for detecting dependence compared with those typically accepted in non-intoxicated individuals. The AUDIT test demonstrates good performance for detecting alcohol abuse and/or alcohol-dependent patients (≥7 for women and ≥12 for men) and for distinguishing alcohol dependence (≥11 for women and ≥14 for men) from other conditions. Conclusion: Our study underscores for the first time the need to adapt, taking into account gender, the thresholds of tests typically used for detection of abuse and dependence in this population. PMID:22414922

[Newborn hearing screening program: association between hearing loss and risk factors].

PubMed

Pereira, Priscila Karla Santana; Martins, Adriana de Souza; Vieira, Márcia Ribeiro; Azevedo, Marisa Frasson de

2007-01-01

Hearing loss in newborns. To verify the prevalence of auditory alterations in newborns of Hospital São Paulo (hospital), observing if there are any correlations with the following variables: birth weight, gestational age, relation weight/gestational age and risk factors for hearing loss. A retrospective analysis of the hospital records of 1696 newborns; 648 records of preterm infants and 1048 records of infants born at term. All of the infants had been submitted to an auditory evaluation consisting of: Transient Otoacoustic Emissions, investigation of the cochleal-palpebral reflexes and acoustic imittance tests, identifying the type and level of hearing loss. Sensorineural hearing loss was identified in .82% of the infants who were born at term and in 3.1% of the preterm infants -- with a statistically significant difference. Conductive hearing loss was the most frequent type of hearing loss in both groups, occurring in 14.6% of the term infants and in 16.3% of the preterm infants. Alteration of the central auditory system was considered as a possible diagnosis for 5.8% of the preterm infants and for 3.3% of the term infants. For the group of infants who were born at term, a significant correlation was observed between failure in the hearing screening test and the presence of risk factors such as family history and presence of a syndrome -- the child who presented a syndrome had 37 times more chances of failing in the hearing screening test and seven times more chances of failing in the right ear when there was a family history for hearing loss. The lower the gestational age (< 30 weeks) and birth weight (< 1500 g), the higher the chances of failing in the hearing screening test (3 times more). Hearing loss had a higher occurrence in preterm infants who remained in the ICU. Gestational age and birth weight were important variables related to the possibility of failure in the hearing screening test. A correlation was observed between the presence of a syndrome and sensorineural hearing loss in infants who were born at term.

Developing Novel Therapeutics Targeting Undifferentiated and Castration-Resistant Prostate Cancer Stem Cells

DTIC Science & Technology

2016-10-01

identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to identify novel PCSC-targeting chemicals. In the past...display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides ; and 2) To perform unbiased drug library screening to...Goals of the Project (SOW): Aim 1: To perform phage display library (PDL) screening in PSA-/lo PCa cells to identify PCSC- specific homing peptides

Technologies for Single-Cell Isolation

PubMed Central

Gross, Andre; Schoendube, Jonas; Zimmermann, Stefan; Steeb, Maximilian; Zengerle, Roland; Koltay, Peter

2015-01-01

The handling of single cells is of great importance in applications such as cell line development or single-cell analysis, e.g., for cancer research or for emerging diagnostic methods. This review provides an overview of technologies that are currently used or in development to isolate single cells for subsequent single-cell analysis. Data from a dedicated online market survey conducted to identify the most relevant technologies, presented here for the first time, shows that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33% usage), laser microdissection (17%), manual cell picking (17%), random seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are currently the most frequently used technologies. These most prominent technologies are described in detail and key performance factors are discussed. The survey data indicates a further increasing interest in single-cell isolation tools for the coming years. Additionally, a worldwide patent search was performed to screen for emerging technologies that might become relevant in the future. In total 179 patents were found, out of which 25 were evaluated by screening the title and abstract to be relevant to the field. PMID:26213926

Chronic headache and potentially modifiable risk factors: screening and behavioral management of sleep disorders.

PubMed

Rains, Jeanetta C

2008-01-01

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.

Frequency and specificity of red blood cell alloimmunization in chilean transfused patients.

PubMed

Caamaño, José; Musante, Evangelina; Contreras, Margarita; Ulloa, Hernán; Reyes, Carolina; Inaipil, Verónica; Saavedra, Nicolás; Guzmán, Neftalí

2015-01-01

Alloimmunization is an adverse effect of blood transfusions. In Chile, alloimmunization frequency is not established, and for this reason the aim of this study was to investigate the prevalence and specificity of red blood cell (RBC) alloantibodies in Chilean transfused subjects. Records from 4,716 multi-transfused patients were analyzed. In these patients, antibody screening was carried out prior to cross-matching with a commercially available two-cell panel by the microcolum gel test, and samples with a positive screen were analyzed for the specificity of the alloantibody with a 16-cell identification panel. The incidence of RBC alloimmunization in transfused patients was 1.02% (48/4,716) with a higher prevalence in women (40/48). We detected 52 antibodies, the most frequent specificities identified were anti-E (30.8%), anti-K (26.9%), anti-D (7.7%), and anti-Fy(a) (5.8%). The highest incidence of alloantibodies was observed in cancer and gastroenterology patients. The data demonstrated a low alloimmunization frequency in Chilean transfused patients, principally associated with antibodies anti-E, anti-K, anti-D, and anti-Fy(a).

Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer.

PubMed

Glöckner, Sabine C; Dhir, Mashaal; Yi, Joo Mi; McGarvey, Kelly E; Van Neste, Leander; Louwagie, Joost; Chan, Timothy A; Kleeberger, Wolfram; de Bruïne, Adriaan P; Smits, Kim M; Khalid-de Bakker, Carolina A J; Jonkers, Daisy M A E; Stockbrügger, Reinhold W; Meijer, Gerrit A; Oort, Frank A; Iacobuzio-Donahue, Christine; Bierau, Katja; Herman, James G; Baylin, Stephen B; Van Engeland, Manon; Schuebel, Kornel E; Ahuja, Nita

2009-06-01

We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.

Technologies for Single-Cell Isolation.

PubMed

Gross, Andre; Schoendube, Jonas; Zimmermann, Stefan; Steeb, Maximilian; Zengerle, Roland; Koltay, Peter

2015-07-24

The handling of single cells is of great importance in applications such as cell line development or single-cell analysis, e.g., for cancer research or for emerging diagnostic methods. This review provides an overview of technologies that are currently used or in development to isolate single cells for subsequent single-cell analysis. Data from a dedicated online market survey conducted to identify the most relevant technologies, presented here for the first time, shows that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33% usage), laser microdissection (17%), manual cell picking (17%), random seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are currently the most frequently used technologies. These most prominent technologies are described in detail and key performance factors are discussed. The survey data indicates a further increasing interest in single-cell isolation tools for the coming years. Additionally, a worldwide patent search was performed to screen for emerging technologies that might become relevant in the future. In total 179 patents were found, out of which 25 were evaluated by screening the title and abstract to be relevant to the field.

A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency.

PubMed

van der Westhuizen, Francois H; Smuts, Izelle; Honey, Engela; Louw, Roan; Schoonen, Maryke; Jonck, Lindi-Maryn; Dercksen, Marli

2018-01-15

Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD type I) is an autosomal recessive disorder of the electron transfer flavoprotein function characterized by a severe clinical and biochemical phenotype, including congenital abnormalities with unresponsiveness to riboflavin treatment as distinguishing features. From a retrospective study, relying mainly on metabolic data, we have identified a novel mutation, c.1067G>A (p.Gly356Glu) in exon 8 of ETFDH, in three South African Caucasian MADD patients with the index patient presenting the hallmark features of type I MADD and two patients with compound heterozygous (c.1067G>A+c.1448C>T) mutations presenting with MADD type III. SDS-PAGE western blot confirmed the significant effect of this mutation on ETFDH structural instability. The identification of this novel mutation in three families originating from the South African Afrikaner population is significant to direct screening and strategies for this disease, which amongst the organic acidemias routinely screened for, is relatively frequently observed in this population group. Copyright © 2017 Elsevier B.V. All rights reserved.

Artificial intelligence for breast cancer screening: Opportunity or hype?

PubMed

Houssami, Nehmat; Lee, Christoph I; Buist, Diana S M; Tao, Dacheng

2017-12-01

Interpretation of mammography for breast cancer (BC) screening can confer a mortality benefit through early BC detection, can miss a cancer that is present or fast growing, or can result in false-positives. Efforts to improve screening outcomes have mostly focused on intensifying imaging practices (double instead of single-reading, more frequent screens, or supplemental imaging) that may add substantial resource expenditures and harms associated with population screening. Less attention has been given to making mammography screening practice 'smarter' or more efficient. Artificial intelligence (AI) is capable of advanced learning using large complex datasets and has the potential to perform tasks such as image interpretation. With both highly-specific capabilities, and also possible un-intended (and poorly understood) consequences, this viewpoint considers the promise and current reality of AI in BC detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Neurogenic oropharyngeal dysphagia is a frequent condition in patients admitted to the ICU].

PubMed

Pedersen, Anette Barbre; Kjærsgaard, Annette; Larsen, Jens Kjærgaard Rolighed; Nielsen, Lars Hedemann

2015-03-02

Neurogenic oropharyngeal dysphagia (NOD) is a frequent condition in neurological patients admitted to the ICU, particularly in patients with brainstem lesions. The CNS damage itself can predispose to dysphagia, but also the treatment and preventive measures may predispose to and exacerbate the condition. Frequent pneumonia in a neurological patient is a warning signal that should cause screening for dysphagia. Complications are serious and can be fatal. Neurological patients should be examined for NOD before decannulation. Treatment is difficult, so prevention and multidisciplinary neurological rehabilitation is important.

Incidence of Sleep Disorders Reported by Patients at UTHSC College of Dentistry: A Two-Year Follow-Up and Proposed Educational Program.

PubMed

Ivanoff, Chris S; Pancratz, Frank

2015-05-01

A 2011 study at one U.S. dental school found that patients were not routinely screened by dental students for obstructive sleep apnea and/or other related sleep disorders, nor were students being trained to screen. Consequently, the medical history questionnaire used in the clinic was updated to include five specific screening questions. The aim of this two-year follow-up study was to determine whether screening had improved at the school. A retrospective chart review of all patients (age 14-70+) in the third- and fourth-year dental clinics in 2012 and 2013 searched for "YES" responses to the five questions. Of 5,931 patients, 38% reported they snore or were told they snore. By age 50-59, their reports of snoring increased to 50%. About 5% reported incidents waking up choking. By age 50, between one-fifth and one-quarter indicated they woke up frequently during the night. One in six frequently felt overly tired during the daytime, often falling asleep. This problem was evenly reported by all age groups between ages 30 and 69. About half the patients reporting sleep problems also had hypertension and cardiovascular problems with an equal distribution between males and females. The results showed that updating the medical history form had dramatically improved screening for sleep-disordered breathing by these dental students. Though screening is neither a definitive diagnosis nor an attempt to distinguish among sleep disorders, the results correlate with national statistics. Screening is an important step to increase student awareness of this serious health trend as it prepares students to engage more constructively in its management and referral.

Operationalizing workplace accommodations for individuals with disabilities: A scoping review.

PubMed

Sundar, Vidya

2017-01-01

The provision of workplace accommodations is a proven strategy in supporting individuals with disabilities at work. Accommodations include a wide range of supports and strategies that are not very well defined beyond the Americans with Disabilities Act in the United States. Understanding the landscape of accommodations is important to measure the impact of programs that support employment of individuals with disabilities. To conduct a scoping review and thematic analysis of research literature to identify how workplace accommodations are operationalized and to identify knowledge gaps in its conceptualization. Keywords searches were conducted in seven electronic databases. Title, abstract, and full text screening was conducted followed by a thematic analysis of the content to identify how workplace accommodations are operationalized. Overall, 47 studies were selected for review. 433 different types of accommodations were identified, of which assistive technology and specialized equipment represented the most frequently reported type of accommodation (40%). A very small percentage of studies included policy changes (9%) and human assistance (5%) as an accommodation strategy. This scoping review aims to clarify how accommodations are operationalized in the research literature. Key knowledge gaps identified include the systematic exclusion of certain types of supports or disability types.

Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast.

PubMed

Peterson, J; Zheng, Y; Bender, L; Myers, A; Cerione, R; Bender, A

1994-12-01

The SH3 domain-containing protein Bem1p is needed for normal bud emergence and mating projection formation, two processes that require asymmetric reorganizations of the cortical cytoskeleton in Saccharomyces cerevisiae. To identify proteins that functionally and/or physically interact with Bem1p, we screened for mutations that display synthetic lethality with a mutant allele of the BEM1 gene and for genes whose products display two-hybrid interactions with the Bem1 protein. CDC24, which is required for bud emergence and encodes a GEF (guanine-nucleotide exchange factor) for the essential Rho-type GTPase Cdc42p, was identified during both screens. The COOH-terminal 75 amino acids of Cdc24p, outside of the GEF domain, can interact with a portion of Bem1p that lacks both SH3 domains. Bacterially expressed Cdc24p and Bem1p bind to each other in vitro, indicating that no other yeast proteins are required for this interaction. The most frequently identified gene that arose from the bem1 synthetic-lethal screen was the bud-emergence gene BEM2 (Bender and Pringle. 1991. Mol. Cell Biol. 11:1295-1395), which is allelic with IPL2 (increase in ploidy; Chan and Botstein, 1993. Genetics. 135:677-691). Here we show that Bem2p contains a GAP (GTPase-activating protein) domain for Rho-type GTPases, and that this portion of Bem2p can stimulate in vitro the GTPase activity of Rho1p, a second essential yeast Rho-type GTPase. Cells deleted for BEM2 become large and multinucleate. These and other genetic, two-hybrid, biochemical, and phenotypic data suggest that multiple Rho-type GTPases control the reorganization of the cortical cytoskeleton in yeast and that the functions of these GTPases are tightly coupled. Also, these findings raise the possibility that Bem1p may regulate or be a target of action of one or more of these GTPases.

Screening for sexually transmitted diseases in rural South African women.

PubMed

Schneider, H; Coetzee, D J; Fehler, H G; Bellingan, A; Dangor, Y; Radebe, F; Ballard, R C

1998-06-01

This paper reports on a study undertaken in a rural area of South Africa, to develop a non-laboratory tool to screen for sexually transmitted diseases (STDs) among family planning clients. A cross sectional study was performed of 249 consecutive women attending a family planning service between November and December 1994. A questionnaire was administered, and a clinical examination and laboratory tests conducted. Sociodemographic, clinical, and other non-laboratory variables that were significantly associated with laboratory evidence of infection were combined to produce non-hierarchical scoring systems for three "syndromes": gonococcal and/or chlamydial cervical infection, trichomoniasis, and cervical infection and/or trichomoniasis combined. The sensitivity, specificity, and predictive values of the scoring systems as a screening tool were assessed against the gold standard of laboratory tests. The prevalence of reproductive tract infections among the study participants was as follows: Chlamydia trachomatis 12%, Neisseria gonorrhoeae 3%, Trichomonas vaginalis 18%, and bacterial vaginosis 29%. Although vaginal discharge and other symptoms were frequently reported, symptoms bore no relation to the presence of infection. The following independent associations with gonococcal/chlamydial cervical infection were found: age less than 25 years and cervical mucopus and/or friability. Abnormal discharge on examination, visible inflammatory changes of the cervix (increased redness), no recent travel, and unemployment were associated with trichomoniasis. The combination of trichomonas and/or cervical infection ("STD syndrome") was associated with cervical mucopus/friability, unemployment, lack of financial support, and increased redness of the cervix. Of the three scoring systems developed on the basis of these associations, that of the "STD syndrome" achieved the best performance characteristics as a screening tool, with a sensitivity of 62%, specificity of 74%, and positive predictive value of 48%. STDs are common in a population of rural, sexually active women attending a family planning service. In resource poor settings, non-laboratory screening tools could play some role in identifying and treating infections in these women, especially since the majority would not otherwise have been reached. However, such screening tools cannot be viewed as the only way to identify STDs and should be considered as part of an overall strategy of STD control that includes, for example, good management of symptomatic individuals and their partners.

School-Based Screening for Suicide Risk: Balancing Costs and Benefits

PubMed Central

Wilcox, Holly; Huo, Yanling; Turner, J. Blake; Fisher, Prudence; Shaffer, David

2010-01-01

Objectives. We examined the effects of a scoring algorithm change on the burden and sensitivity of a screen for adolescent suicide risk. Methods. The Columbia Suicide Screen was used to screen 641 high school students for high suicide risk (recent ideation or lifetime attempt and depression, or anxiety, or substance use), determined by subsequent blind assessment with the Diagnostic Interview Schedule for Children. We compared the accuracy of different screen algorithms in identifying high-risk cases. Results. A screen algorithm comprising recent ideation or lifetime attempt or depression, anxiety, or substance-use problems set at moderate-severity level classed 35% of students as positive and identified 96% of high-risk students. Increasing the algorithm's threshold reduced the proportion identified to 24% and identified 92% of high-risk cases. Asking only about recent suicidal ideation or lifetime suicide attempt identified 17% of the students and 89% of high-risk cases. The proportion of nonsuicidal diagnosis–bearing students found with the 3 algorithms was 62%, 34%, and 12%, respectively. Conclusions. The Columbia Suicide Screen threshold can be altered to reduce the screen-positive population, saving costs and time while identifying almost all students at high risk for suicide. PMID:20634467

Systematic health screening of refugees after resettlement in recipient countries: a scoping review.

PubMed

Hvass, Anne Mette Fløe; Wejse, Christian

2017-08-01

Health screening of refugees after settlement in a recipient country is an important tool to find and treat diseases. Currently, there are no available reviews on refugee health screening after resettlement. A systematic literature search was conducted using the online Medical Literature Analysis and Retrieval System ('MEDLINE') database. Data extraction and synthesis were performed according to the PRISMA statement. The search retrieved 342 articles. Relevance screening was conducted on all abstracts/titles. The final 53 studies included only original scientific articles on health screening of refugees conducted after settlement in another country. The 53 studies were all from North America, Australia/New Zealand and Europe. Because of differences in country policies, the screenings were conducted differently in the various locations. The studies demonstrated great variation in who was targeted for screening and how screening was conducted. The disease most frequently screened for was tuberculosis; this was done in approximately half of the studies. Few studies included screening for mental health and non-infectious diseases like diabetes and hypertension. Health screening of refugees after resettlement is conducted according to varying local policies and there are vast differences in which health conditions are covered in the screening and whom the screening is available to.

Inhibition of Ras for cancer treatment: the search continues

PubMed Central

Baines, Antonio T.; Xu, Dapeng; Der, Channing J.

2012-01-01

Background The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Discussion Despite intensive effort, to date no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Conclusions Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery. PMID:22004085

Nutritional risk amongst community-living Maori and non-Maori older people in Hawke's Bay.

PubMed

McElnay, Caroline; Marshall, Bob; O'Sullivan, Jessica; Jones, Lisa; Ashworth, Tracy; Hicks, Karen; Forrest, Rachel

2012-12-01

Maintaining good nutrition is vital for healthy ageing. Poor nutrition increases the risk of hospitalisation, disability and mortality. Research shows clinical malnutrition is preceded by a state of nutritional risk and screening can identify older people at risk of poor nutrition or who currently have impaired nutritional status. To assess the population prevalence of nutritional risk amongst community-living Maori and non-Maori older people in Hawke's Bay. A postal survey of 1268 people aged 65 years or older on the electoral roll for Hawke's Bay was conducted. Nutritional risk was measured using the SCREEN II questionnaire. Responses from 473 people were received (43.8% male, 49.9% female, 6.3% unspecified) with an estimated average age of 74 years. Nutritional risk was present amongst 56.5% of older people with 23.7% at risk and 32.8% at high risk. Maori were 5.2 times more likely to be at nutritional risk than non-Maori. Older people living alone were 3.5 times more likely to be at nutritional risk than those living with others. The most frequent risk factors were low milk-product intake, perception of own weight being more or less than it should be, and low meat and alternatives intake. Skipping meals and low fruit and vegetable intake were additional frequent risk factors for Maori. Both living situation and ethnicity are associated with nutritional risk. Further investigation is needed to confirm these findings and to determine issues specific for older Maori, including barriers to good nutrition and opportunities for nutritional improvement.

Physician visits and preventive care among Asian American and Pacific Islander long-term survivors of colorectal cancer, USA, 1996-2006.

PubMed

Steele, C Brooke; Townsend, Julie S; Tai, Eric; Thomas, Cheryll C

2014-03-01

Published literature on receipt of preventive healthcare services among Asian American and Pacific Islander (API) cancer survivors is scarce. We describe patterns in receipt of preventive services among API long-term colorectal cancer (CRC) survivors. Surveillance, Epidemiology, and End Results registry-Medicare data were used to identify 9,737 API and white patients who were diagnosed with CRC during 1996-2000 and who survived 5 or more years beyond their diagnoses. We examined receipt of vaccines, mammography (females), bone densitometry (females), and cholesterol screening among the survivors and how the physician specialties they visited for follow-up care correlated to services received. APIs were less likely than whites to receive mammography (52.0 vs. 69.3 %, respectively; P < 0.0001) but more likely to receive influenza vaccine, cholesterol screening, and bone densitometry. These findings remained significant in our multivariable model, except for receipt of bone densitometry. APIs visited PCPs only and both PCPs and oncologists more frequently than whites (P < 0.0001). Women who visited both PCPs and oncologists compared with PCPs only were more likely to receive mammography (odds ratio = 1.40; 95 % confidence interval, 1.05-1.86). Visits to both PCPs and oncologists were associated with increased use of mammography. Although API survivors visited these specialties more frequently than white survivors, API women may need culturally appropriate outreach to increase their use of this test. Long-term cancer survivors need to be aware of recommended preventive healthcare services, as well as who will manage their primary care and cancer surveillance follow-up.

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

PubMed

Hadzsiev, Kinga; Polgar, Noemi; Bene, Judit; Komlosi, Katalin; Karteszi, Judit; Hollody, Katalin; Kosztolanyi, Gyorgy; Renieri, Alessandra; Melegh, Bela

2011-03-01

Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C >T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G >T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G >T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations.

Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d.

PubMed

Doxey, Andrew C; Cheng, Zhenyu; Moffatt, Barbara A; McConkey, Brendan J

2010-08-03

Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins. The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.

Is chest x-ray an adequate screening tool for the diagnosis of blunt thoracic aortic injury?

PubMed

Ekeh, Akpofure Peter; Peterson, Wylan; Woods, Randy J; Walusimbi, Mbaga; Nwuneli, Nancy; Saxe, Jonathan M; McCarthy, Mary C

2008-11-01

Blunt thoracic aortic injuries (BTAI) have a high mortality rate. For survivors, chest X-ray (CXR) findings are used to determine the need for further diagnostic testing with chest computerized tomography with angiography (CTA) or conventional angiography. We set to determine the adequacy of utilizing CXR alone as a screening tool for BTAI. All patients diagnosed with BTAI at a level I trauma-center during a 7-year-period were identified. CXRs of these patients and those of a control group of blunt trauma patients with an injury severity score >15 were reviewed by four trauma surgeons blinded to the diagnosis. Based on each CXR viewed, the surgeons decided if they would have proceeded to chest CTA, angiography, or required no further studies to rule out BTAI. In the 7-year-period, 83 patients had BTAI. CXRs were available in 45 patients. The four surgeons viewed 96 CXRs including those of 51 controls. Based on the CXR appearance in patients with BTAI, the surgeons chose to proceed to chest CTA in 38 patients (84.4%), conventional aortography in two patients (4.4%), and no further testing in five patients (11.2%). A widened mediastinum (75%) and loss of the aorto-pulmonary window (40%) were the most frequent CXR abnormalities. Patients with BTAI were more likely to have an abnormal CXR-40 of 45 (88.8%) patients when compared with the controls-25 of 51 (49%)patients-p < 0.001. Although CXR is a sensitive screening modality, it failed to identify the possibility of BTAI in 11% of patients. The liberal use of chest CTA after high speed motor vehicle crashes is recommended to minimize the incidence of missed BTAI.

AB003. Validation of a two-stage screening model to predict moderate to severe obstructive sleep apnea in chronic tetraplegia

PubMed Central

Graco, Marnie; Cross, Susan; Thiyagarajan, Chinnaya; Shafazand, Shirin; Ayas, Najib; Schembri, Rachel; Booker, Lauren; Nicholls, Carmel; Burns, Patricia; Nash, Mark; Green, Sally; Berlowitz, David J.

2018-01-01

Background Prevalence of obstructive sleep apnea (OSA) in people with chronic spinal cord injury (SCI) is estimated at between 28% and 77%. Current guidelines recommend polysomnography (PSG) for all people with SCI and symptoms of OSA. However, PSG is a resource intensive and frequently inaccessible test, especially in SCI. A two-stage model of questionnaire followed by overnight oximetry has been found to accurately detect moderate to severe OSA in the able-bodied. To determine whether a similar two-stage model can detect moderate to severe OSA in chronic tetraplegia. Methods An existing dataset of 78 people with tetraplegia was examined to determine predictors of OSA for inclusion in a new questionnaire. Cut-offs for the model were estimated with receiver operating characteristics (ROC) curve analysis. Model accuracy was evaluated prospectively in 100 participants with chronic, traumatic tetraplegia across four international SCI units. Results Multivariate analysis identified injury completeness, age, sleepiness, self-reported snoring and apneas for the new questionnaire [ROC area under curve (AUC) 0.87 (95% CI: 0.79–0.95)]. Oxygen desaturation index was also highly predictive [0.93 (0.87–0.98)]. The two-stage model had a sensitivity and specificity of 83% (66–93%) and 88% (75–94%) in the development group (n=78), and 77% (65–87%) and 81% (68–90%) in the validation group (n=100). Conclusions The two-stage screening model provides an accurate and translatable alternative to full PSG for identifying moderate to severe OSA in people with chronic tetraplegia. Implementation of this screening model could substantially increase the detection of OSA in tetraplegia and improve access to treatments.

Chromatin Landscapes of Retroviral and Transposon Integration Profiles

PubMed Central

Badhai, Jitendra; Rust, Alistair G.; Rad, Roland; Hilkens, John; Berns, Anton; van Lohuizen, Maarten; Wessels, Lodewyk F. A.; de Ridder, Jeroen

2014-01-01

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of to unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%–33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes. PMID:24721906

Validity of Targeted Next-Generation Sequencing in Routine Care for Identifying Clinically Relevant Molecular Profiles in Non-Small-Cell Lung Cancer: Results of a 2-Year Experience on 1343 Samples.

PubMed

Legras, Antoine; Barritault, Marc; Tallet, Anne; Fabre, Elizabeth; Guyard, Alice; Rance, Bastien; Digan, William; Pecuchet, Nicolas; Giroux-Leprieur, Etienne; Julie, Catherine; Jouveshomme, Stéphane; Duchatelle, Véronique; Giraudet, Véronique; Gibault, Laure; Cazier, Alain; Pastre, Jean; Le Pimpec-Barthes, Françoise; Laurent-Puig, Pierre; Blons, Hélène

2018-05-19

Theranostic assays are based on single-gene testing, but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single-gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations, and NGS mutation profiles were analyzed on a large series of non-small-cell lung cancers (n = 1343). The R 2 correlation between expected and measured allelic ratio, using commercial samples, was >0.96. Mutation detection threshold was 2% for 10 ng of DNA input. κ Scores for TaqMan versus NGS were 0.99 (95% CI, 0.97-1.00) for EGFR and 0.98 (95% CI, 0.97-1.00) for KRAS after exclusion of rare EGFR (n = 40) and KRAS (n = 60) mutations. NGS identified 693 and 292 mutations in validated and potential oncogenic drivers, respectively. Significant associations were found between EGFR and PI3KCA or CTNNB1 and between KRAS and STK11. Potential oncogenic driver mutations or gene amplifications were more frequent in validated oncogenic driver nonmutated samples. This work is a proof of concept that targeted NGS is accessible in routine screening, including large screening, at reasonable cost. Clinical data should be collected and implemented in specific databases to make molecular data meaningful for direct patients' benefit. Copyright © 2018. Published by Elsevier Inc.

Identification and Characterization of Small-Molecule Inhibitors of the R132H/R132H Mutant Isocitrate Dehydrogenase 1 Homodimer and R132H/Wild-Type Heterodimer.

PubMed

Brooks, Eric; Wu, Xiang; Hanel, Art; Nguyen, Shaun; Wang, Jing; Zhang, Jeffrey H; Harrison, Amanda; Zhang, Wentao

2014-09-01

Recurrent genetic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been identified in multiple tumor types. The most frequent mutation, IDH1 R132H, is a gain-of-function mutation resulting in an enzyme-catalyzing conversion of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). A high-throughput assay quantifying consumption of NADPH by IDH1 R132H has been optimized and implemented to screen 3 million compounds in 1536-well formats. The primary high-throughput screening hits were further characterized by RapidFire-mass spectrometry measuring 2-HG directly. Multiple distinct chemotypes were identified with nanomolar potencies (6-300 nM). All inhibitors were found to be inactive against the wild-type IDH1 homodimers. An IDH1 heterodimer between wild-type and R132H mutant is capable of catalyzing conversion of α-KG to 2-HG and isocitrate to α-KG. Interestingly, one of the inhibitors, EXEL-9324, was found to inhibit both conversions by the IDH1 heterodimer. This indicates the R132H/WT heterodimer may adopt conformations distinct from that of the R132H/R132H homodimer. Further enzymatic studies support this conclusion as the heterodimer exhibited a significantly lower apparent Michaelis-Menten constant for α-KG (K(m)=110 µM) compared with the R132H homodimer (K(m)= 1200 µM). The enhanced apparent affinity for α-KG suggests R132H/WT heterodimeric IDH1 can produce 2-HG more efficiently at normal intracellular levels of α-KG (approximately 100 µM). © 2014 Society for Laboratory Automation and Screening.

Screening for illicit and medicinal drugs in whole blood using fully automated SPE and ultra-high-performance liquid chromatography with TOF-MS with data-independent acquisition.

PubMed

Pedersen, Anders Just; Dalsgaard, Petur Weihe; Rode, Andrej Jaroslav; Rasmussen, Brian Schou; Müller, Irene Breum; Johansen, Sys Stybe; Linnet, Kristian

2013-07-01

A broad forensic screening method for 256 analytes in whole blood based on a fully automated SPE robotic extraction and ultra-high-performance liquid chromatography (UHPLC) with TOF-MS with data-independent acquisition has been developed. The limit of identification was evaluated for all 256 compounds and 95 of these compounds were validated with regard to matrix effects, extraction recovery, and process efficiency. The limit of identification ranged from 0.001 to 0.1 mg/kg, and the process efficiency exceeded 50% for 73 of the 95 analytes. As an example of application, 1335 forensic traffic cases were analyzed with the presented screening method. Of these, 992 cases (74%) were positive for one or more traffic-relevant drugs above the Danish legal limits. Commonly abused drugs such as amphetamine, cocaine, and frequent types of benzodiazepines were the major findings. Nineteen less frequently encountered drugs were detected e.g. buprenorphine, butylone, cathine, fentanyl, lysergic acid diethylamide, m-chlorophenylpiperazine, 3,4-methylenedioxypyrovalerone, mephedrone, 4-methylamphetamine, p-fluoroamphetamine, and p-methoxy-N-methylamphetamine. In conclusion, using UHPLC-TOF-MS screening with data-independent acquisition resulted in the detection of common drugs of abuse as well as new designer drugs and more rarely occurring drugs. Thus, TOF-MS screening of blood samples constitutes a practical way for screening traffic cases, with the exception of δ-9-tetrahydrocannabinol, which should be handled in a separate method. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Malnutrition in Hospitalized Pediatric Patients: Assessment, Prevalence, and Association to Adverse Outcomes.

PubMed

Daskalou, Efstratia; Galli-Tsinopoulou, Assimina; Karagiozoglou-Lampoudi, Thomais; Augoustides-Savvopoulou, Persefone

2016-01-01

Malnutrition is a frequent finding in pediatric health care settings in the form of undernutrition or excess body weight. Its increasing prevalence and impact on overall health status, which is reflected in the adverse outcomes, renders imperative the application of commonly accepted and evidence-based practices and tools by health care providers. Nutrition risk screening on admission and nutrition status evaluation are key points during clinical management of hospitalized pediatric patients, in order to prevent health deterioration that can lead to serious complications and growth consequences. In addition, anthropometric data based on commonly accepted universal growth standards can give accurate results for nutrition status. Both nutrition risk screening and nutrition status assessment are techniques that should be routinely implemented, based on commonly accepted growth standards and methodology, and linked to clinical outcomes. The aim of the present review was to address the issue of hospital malnutrition in pediatric settings in terms of prevalence, outline nutrition status evaluation and nutrition screening process using different criteria and available tools, and present its relationship with outcome measures. Key teaching points • Malnutrition-underweight or excess body weight-is a frequent imbalance in pediatric settings that affects physical growth and results in undesirable clinical outcomes. • Anthropometry interpretation through growth charts and nutrition screening are cornerstones for the assessment of malnutrition.To date no commonly accepted anthropometric criteria or nutrition screening tools are used in hospitalized pediatric patients. • Commonly accepted nutrition status and screening processes based on the World Health Organization's growth standards can contribute to the overall hospital nutrition care of pediatric patients.

Examining the Influence of Cost Concern and Awareness of Low-cost Health Care on Cancer Screening among the Medically Underserved.

PubMed

Best, Alicia L; Strane, Alcha; Christie, Omari; Bynum, Shalanda; Wiltshire, Jaqueline

2017-01-01

African Americans suffer a greater burden of mortality from breast, cervical, and colorectal cancers than other groups in the United States. Early detection through timely screening can improve survival outcomes; however, cost is frequently reported as a barrier to screening. Federally qualified health centers (FQHCs) provide preventive and primary care to underserved populations regardless of ability to pay, positioning them to improve cancer screening rates. The purpose of this study was to examine the influence of concern about health care cost (cost concern) and awareness of low-cost health care (awareness) on cancer screening among 236 African Americans within an FQHC service area using self-report surveys. Multiple logistic regression indicated that awareness was positively associated with cervical and colorectal cancer screening, while cost concern was negatively associated with mammography screening. Results indicate that improving awareness and understanding of low-cost health care could increase cancer screening among underserved African Americans.

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

PubMed Central

Karlowsky, James A.; Kazmierczak, Krystyna M.; Badal, Robert E.; Young, Katherine; Motyl, Mary R.; Sahm, Daniel F.

2017-01-01

ABSTRACT The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 μg/ml; n = 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-β-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.4% (1,493/103,960) of all isolates of Enterobacteriaceae. The most frequently identified carbapenemase genes were the KPC (n = 794), OXA-48-like (n = 300), and NDM (n = 290) genes. Carbapenemase genes were most frequently identified in Klebsiella pneumoniae (n = 1,127), Escherichia coli (n = 149), and Enterobacter cloacae (n = 110). Among the carbapenemase-positive isolates, 66.7% (2/3), 37.0% (111/300), 20.0% (8/40), 3.3% (3/92), 2.3% (18/794), and 0% (0/290) of the isolates with genes for GES, OXA-48-like, IMP, VIM, KPC, and NDM, respectively, were susceptible to imipenem (MIC, ≤1 μg/ml). Isolates that tested as susceptible to imipenem were not uncommon among carbapenemase-positive isolates (9.4%, 141/1,493) and most frequently carried OXA-48-like enzymes (78.7%; 111/141); however, overall, these isolates remained rare (0.1%, 141/103,960). The practice of screening clinical isolates of Enterobacteriaceae that test as susceptible to carbapenems in vitro for the presence of carbapenemase genes remains controversial and requires further study. PMID:28298454

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014.

PubMed

Karlowsky, James A; Lob, Sibylle H; Kazmierczak, Krystyna M; Badal, Robert E; Young, Katherine; Motyl, Mary R; Sahm, Daniel F

2017-06-01

The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 μg/ml; n = 3,428) and 9,371 isolates of Escherichia coli , Klebsiella pneumoniae , Klebsiella oxytoca , and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-β-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.4% (1,493/103,960) of all isolates of Enterobacteriaceae The most frequently identified carbapenemase genes were the KPC ( n = 794), OXA-48-like ( n = 300), and NDM ( n = 290) genes. Carbapenemase genes were most frequently identified in Klebsiella pneumoniae ( n = 1,127), Escherichia coli ( n = 149), and Enterobacter cloacae ( n = 110). Among the carbapenemase-positive isolates, 66.7% (2/3), 37.0% (111/300), 20.0% (8/40), 3.3% (3/92), 2.3% (18/794), and 0% (0/290) of the isolates with genes for GES, OXA-48-like, IMP, VIM, KPC, and NDM, respectively, were susceptible to imipenem (MIC, ≤1 μg/ml). Isolates that tested as susceptible to imipenem were not uncommon among carbapenemase-positive isolates (9.4%, 141/1,493) and most frequently carried OXA-48-like enzymes (78.7%; 111/141); however, overall, these isolates remained rare (0.1%, 141/103,960). The practice of screening clinical isolates of Enterobacteriaceae that test as susceptible to carbapenems in vitro for the presence of carbapenemase genes remains controversial and requires further study. Copyright © 2017 American Society for Microbiology.

A Literature Review of Cervical Cancer Screening in Transgender Men.

PubMed

Gatos, Kayla C

2018-02-01

Most female-to-male (FTM) transgender men retain their cervixes and need comprehensive sexual health care, including cervical cancer screening. According to the literature, FTM individuals obtain cervical cancer screening less frequently and are less likely to be up to date on their Pap tests compared with cisgender women. Misinformation related to human papillomavirus and cervical cancer risk was noted for health care providers and FTM individuals. Absence of transgender-specific guidelines or trained health care providers presents barriers to cervical cancer screening for FTM individuals, and further research is indicated to develop comprehensive guidelines unique to the needs and experiences of this population. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

Postpartum Support International

MedlinePlus

... Traumatic Stress Disorder Bipolar Mood Disorders Postpartum Psychosis Social Support Online Training Tools for Mom Frequently Asked Questions Screening Recommendations Useful Links Media Family International Father’s Mental Health Day Dads for World ...

Performance characteristics of the PTSD Checklist in retired firefighters exposed to the World Trade Center disaster.

PubMed

Chiu, Sydney; Webber, Mayris P; Zeig-Owens, Rachel; Gustave, Jackson; Lee, Roy; Kelly, Kerry J; Rizzotto, Linda; McWilliams, Rita; Schorr, John K; North, Carol S; Prezant, David J

2011-05-01

Since the World Trade Center (WTC) attacks on September 11, 2001, the Fire Department, City of New York Monitoring Program has provided physical and mental health screening services to rescue/recovery workers. This study evaluated performance of the self-report PTSD Checklist (PCL) as a screening tool for risk of posttraumatic stress disorder (PTSD) in firefighters who worked at Ground Zero, compared with the interviewer-administered Diagnostic Interview Schedule (DIS). From December 2005 to July 2007, all retired firefighter enrollees completed the PCL and DIS on the same day. Sensitivity, specificity, receiver operating characteristic (ROC) curves, and Youden index (J) were used to assess properties of the PCL and to identify an optimum cutoff score. Six percent of 1,915 retired male firefighters were diagnosed with PTSD using the DIS to assess DSM-IV criteria. Depending on the PCL cutoff, the prevalence of elevated risk relative to DSM-IV criteria varied from 16% to 22%. Youden index identified an optimal cutoff score of 39, in contrast with the frequently recommended cutoff of 44. At 39, PCL sensitivity was 0.85, specificity was 0.82, and the area under the ROC curve was 0.91 relative to DIS PTSD diagnosis. This is the first study to validate the PCL in retired firefighters and determine the optimal cutoff score to maximize opportunities for PTSD diagnosis and treatment.

Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X-Linked Kabuki Syndrome Subtype 2.

PubMed

Bögershausen, Nina; Gatinois, Vincent; Riehmer, Vera; Kayserili, Hülya; Becker, Jutta; Thoenes, Michaela; Simsek-Kiper, Pelin Özlem; Barat-Houari, Mouna; Elcioglu, Nursel H; Wieczorek, Dagmar; Tinschert, Sigrid; Sarrabay, Guillaume; Strom, Tim M; Fabre, Aurélie; Baynam, Gareth; Sanchez, Elodie; Nürnberg, Gudrun; Altunoglu, Umut; Capri, Yline; Isidor, Bertrand; Lacombe, Didier; Corsini, Carole; Cormier-Daire, Valérie; Sanlaville, Damien; Giuliano, Fabienne; Le Quan Sang, Kim-Hanh; Kayirangwa, Honorine; Nürnberg, Peter; Meitinger, Thomas; Boduroglu, Koray; Zoll, Barbara; Lyonnet, Stanislas; Tzschach, Andreas; Verloes, Alain; Di Donato, Nataliya; Touitou, Isabelle; Netzer, Christian; Li, Yun; Geneviève, David; Yigit, Gökhan; Wollnik, Bernd

2016-09-01

Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype-genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients. © 2016 WILEY PERIODICALS, INC.

Identification of Potent Chemotypes Targeting Leishmania major Using a High-Throughput, Low-Stringency, Computationally Enhanced, Small Molecule Screen

PubMed Central

Sharlow, Elizabeth R.; Close, David; Shun, Tongying; Leimgruber, Stephanie; Reed, Robyn; Mustata, Gabriela; Wipf, Peter; Johnson, Jacob; O'Neil, Michael; Grögl, Max; Magill, Alan J.; Lazo, John S.

2009-01-01

Patients with clinical manifestations of leishmaniasis, including cutaneous leishmaniasis, have limited treatment options, and existing therapies frequently have significant untoward liabilities. Rapid expansion in the diversity of available cutaneous leishmanicidal chemotypes is the initial step in finding alternative efficacious treatments. To this end, we combined a low-stringency Leishmania major promastigote growth inhibition assay with a structural computational filtering algorithm. After a rigorous assay validation process, we interrogated ∼200,000 unique compounds for L. major promastigote growth inhibition. Using iterative computational filtering of the compounds exhibiting >50% inhibition, we identified 553 structural clusters and 640 compound singletons. Secondary confirmation assays yielded 93 compounds with EC50s ≤ 1 µM, with none of the identified chemotypes being structurally similar to known leishmanicidals and most having favorable in silico predicted bioavailability characteristics. The leishmanicidal activity of a representative subset of 15 chemotypes was confirmed in two independent assay formats, and L. major parasite specificity was demonstrated by assaying against a panel of human cell lines. Thirteen chemotypes inhibited the growth of a L. major axenic amastigote-like population. Murine in vivo efficacy studies using one of the new chemotypes document inhibition of footpad lesion development. These results authenticate that low stringency, large-scale compound screening combined with computational structure filtering can rapidly expand the chemotypes targeting in vitro and in vivo Leishmania growth and viability. PMID:19888337

Classifying obstructive sleep apnea using smartphones.

PubMed

Al-Mardini, Mamoun; Aloul, Fadi; Sagahyroon, Assim; Al-Husseini, Luai

2014-12-01

Obstructive sleep apnea (OSA) is a serious sleep disorder which is characterized by frequent obstruction of the upper airway, often resulting in oxygen desaturation. The serious negative impact of OSA on human health makes monitoring and diagnosing it a necessity. Currently, polysomnography is considered the gold standard for diagnosing OSA, which requires an expensive attended overnight stay at a hospital with considerable wiring between the human body and the system. In this paper, we implement a reliable, comfortable, inexpensive, and easily available portable device that allows users to apply the OSA test at home without the need for attended overnight tests. The design takes advantage of a smatrphone's built-in sensors, pervasiveness, computational capabilities, and user-friendly interface to screen OSA. We use three main sensors to extract physiological signals from patients which are (1) an oximeter to measure the oxygen level, (2) a microphone to record the respiratory effort, and (3) an accelerometer to detect the body's movement. Finally, we examine our system's ability to screen the disease as compared to the gold standard by testing it on 15 samples. The results showed that 100% of patients were correctly identified as having the disease, and 85.7% of patients were correctly identified as not having the disease. These preliminary results demonstrate the effectiveness of the developed system when compared to the gold standard and emphasize the important role of smartphones in healthcare. Copyright © 2014 Elsevier Inc. All rights reserved.

Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.

PubMed

Chong, Irene Yushing; Aronson, Lauren; Bryant, Hanna; Gulati, Aditi; Campbell, James; Elliott, Richard; Pettitt, Stephen; Wilkerson, Paul; Lambros, Maryou B; Reis-Filho, Jorge S; Ramessur, Anisha; Davidson, Michael; Chau, Ian; Cunningham, David; Ashworth, Alan; Lord, Christopher J

2017-08-22

Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets. By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in MYC amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G 1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453). NCT02884453; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990-2011.

PubMed

Bikdeli, Behnood; Punnanithinont, Natdanai; Akram, Yasir; Lee, Ike; Desai, Nihar R; Ross, Joseph S; Krumholz, Harlan M

2017-03-21

Surrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. We identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine , Lancet , and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high-impact journals. Although cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high-profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation.

PubMed

Shammas, Christos; Byrou, Stefania; Phelan, Marie M; Toumba, Meropi; Stylianou, Charilaos; Skordis, Nicos; Neocleous, Vassos; Phylactou, Leonidas A

2016-04-01

Congenital adrenal hyperplasia (CAH) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most commonclinical feature in non-classic CAH patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAH (NC-CAH), 11β-hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. Screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAH. It wasobserved that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAH. A total of 23 NC-CAH female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.Val484Asp, was identified in a patient with CAH in the heterozygous state. The structural characterization of the novel p.Val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAH even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAH.

PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of Léri-Weill dyschondrosteosis (LWD) probands.

PubMed

Benito-Sanz, Sara; del Blanco, Darya Gorbenko; Aza-Carmona, Miriam; Magano, Luis F; Lapunzina, Pablo; Argente, Jesús; Campos-Barros, Angel; Heath, Karen E

2006-10-01

Léri-Weill dyschondrosteosis (LWD) is a skeletal dysplasia characterized by disproportionate short stature and Madelung deformity. Mutations or deletions of the SHOX gene have been previously identified as the main cause of LWD. We recently identified the existence of a second class of pseudoautosomal region 1 (PAR1) deletions which do not include SHOX, implicated in the etiopathogenesis of LWD. The deletions map at least 30-250 kb downstream of SHOX, are variable in size and clearly cosegregate with the LWD phenotype. In order to determine the frequency of this new type of deletions in the Spanish population we analyzed the distribution of PAR1 defects, including the screening of SHOX deletions, mutations, and PAR1 deletions downstream of SHOX, in a total of 26 LWD probands by a combination of MLPA, microsatellite analysis, SNP genotyping, dHPLC, and DNA sequencing. A molecular defect was identified in 16/26 LWD patients (61.5%): 10 PAR1 deletions downstream of SHOX, four SHOX encompassing deletions, and two SHOX mutations. No apparent phenotypic differences were observed between patients with SHOX defects and those with PAR1 deletions downstream of SHOX. In the examined cohort of Spanish LWD probands, PAR1 deletions downstream of SHOX represent the highest proportion of identified mutations (38%) compared to SHOX deletions (15%) and mutations (8%). As a consequence of our findings, the screening of this region should be included in the routine genetic testing of LWD. Also, LWD patients who tested negative for SHOX defects should be re-evaluated for PAR1 deletions downstream of SHOX.

Diagnostic accuracy of administrative data algorithms in the diagnosis of osteoarthritis: a systematic review.

PubMed

Shrestha, Swastina; Dave, Amish J; Losina, Elena; Katz, Jeffrey N

2016-07-07

Administrative health care data are frequently used to study disease burden and treatment outcomes in many conditions including osteoarthritis (OA). OA is a chronic condition with significant disease burden affecting over 27 million adults in the US. There are few studies examining the performance of administrative data algorithms to diagnose OA. The purpose of this study is to perform a systematic review of administrative data algorithms for OA diagnosis; and, to evaluate the diagnostic characteristics of algorithms based on restrictiveness and reference standards. Two reviewers independently screened English-language articles published in Medline, Embase, PubMed, and Cochrane databases that used administrative data to identify OA cases. Each algorithm was classified as restrictive or less restrictive based on number and type of administrative codes required to satisfy the case definition. We recorded sensitivity and specificity of algorithms and calculated positive likelihood ratio (LR+) and positive predictive value (PPV) based on assumed OA prevalence of 0.1, 0.25, and 0.50. The search identified 7 studies that used 13 algorithms. Of these 13 algorithms, 5 were classified as restrictive and 8 as less restrictive. Restrictive algorithms had lower median sensitivity and higher median specificity compared to less restrictive algorithms when reference standards were self-report and American college of Rheumatology (ACR) criteria. The algorithms compared to reference standard of physician diagnosis had higher sensitivity and specificity than those compared to self-reported diagnosis or ACR criteria. Restrictive algorithms are more specific for OA diagnosis and can be used to identify cases when false positives have higher costs e.g. interventional studies. Less restrictive algorithms are more sensitive and suited for studies that attempt to identify all cases e.g. screening programs.

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.

PubMed

Landais, Igor; Hiddingh, Sanne; McCarroll, Matthew; Yang, Chao; Sun, Aiming; Turker, Mitchell S; Snyder, James P; Hoatlin, Maureen E

2009-12-31

The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.

Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors

PubMed Central

2009-01-01

Background The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity. Results Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells. Conclusions These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds. PMID:20043851

Infectious disease profiles of Syrian and Eritrean migrants presenting in Europe: A systematic review.

PubMed

Isenring, Egon; Fehr, Jan; Gültekin, Nejla; Schlagenhauf, Patricia

2018-04-24

In the past decade, a large influx of migrants presented in Europe. Their country of origin was mainly either Syria or Eritrea. Public health institutions in host countries in Europe are challenged to screen and care for migrant populations with regard to infectious diseases. We performed a systematic literature review (according to PRISMA guidelines) to define the infectious disease profile of migrants originating in Syria and Eritrea. The search resulted in 825 papers of possible relevance for infectious diseases in migrants from Syria, of which, after screening, we included 35 in the systematic review. A further 265 papers of possible relevance for infectious diseases in Eritrean migrants were screened, of which we included 27 in the systematic review. In migrants from Syria, leishmaniasis was the most frequently reported infectious disease. In addition, colonisation with drug resistant, Gram-negativ bacteria was reported. In the Eritrean migrants the infectious disease most described in the selected papers was louse-borne relapsing fever. Other frequently reported infectious diseases were scabies and Plasmodium vivax malaria. Our systematic analysis defines the profiles of infectious diseases for migrants from Syria and Eritrea and serves as an evidence base for public health screening and care of presenting migrants. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Video Games, Internet and Social Networks: A Study among French School students

PubMed

Dany, Lionel; Moreau, Laure; Guillet, Clémentine; Franchina, Carmelo

2016-11-25

Aim : Screen-based media use is gradually becoming a public health issue, especially among young people.Method : A local descriptive observational study was conducted in 11 colleges of the Bouches-du-Rhône department. All middle high school students were asked to fill in a questionnaire comprising questions about their demographic characteristics, their screen-based media use (Internet, video games, social networks), any problematic use (video games and social networks), self-esteem and quality of life.Results : A total of 950 college students (mean age : 12.96 years) participated in the research. The results show a high level and a very diverse screen-based media use. Boys more frequently played video games and girls go more frequently used social networks. The levels of problematic use were relatively low for all middle high school students. The level of problematic video game use was significantly higher in boys, and the level of problematic social network use was higher in girls.Conclusion : Differences in the use of video games or social networks raise the general issue of gender differences in society. This study indicates the need for more specific preventive interventions for screen-based media use. The addictive “nature” of certain practices needs to be studied in more detail.

Employees with Epilepsy

MedlinePlus

... can be exacerbated by light sources such as computer screens or fluorescent lights. Use a flicker-free ... cubicle shield Allow frequent breaks from tasks involving computer Provide alternative light sources: Replace fluorescent lights with ...

The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

PubMed

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

2014-09-01

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

PTSD in Latino patients: illness beliefs, treatment preferences, and implications for care.

PubMed

Eisenman, David P; Meredith, Lisa S; Rhodes, Hilary; Green, Bonnie L; Kaltman, Stacey; Cassells, Andrea; Tobin, Jonathan N

2008-09-01

Little is known about how Latinos with post-traumatic stress disorder (PTSD) understand their illness and their preferences for mental health treatment. To understand the illness beliefs and treatment preferences of Latino immigrants with PTSD. Semi-structured, face-to-face interviews. Sixty foreign-born, Latino adults recruited from five primary care centers in New York and New Jersey and screened for PTSD. Content analytic methods identified common themes, their range, and most frequent or typical responses. Participants identified their primary feelings as sadness, anxiety, nervousness, and fear. The most common feeling was "sad" (triste). Other words frequently volunteered were "angry" (enojada), "nervous" (nerviosa), and "scared" (miedo). Participants viewed their PTSD as impairing health and functioning. They ascribed their somatic symptoms and their general medical problems to the "stress" from the trauma and its consequences on their lives. The most common reason participants volunteered for their work and school functioning being impaired was their poor concentration, often due to intrusive thoughts. Most expressed their desire to receive mental health treatment, to receive it within their primary care center, and preferred psychotherapy over psychotropic medications. Among participants who did not report wanting treatment, most said it was because the trauma was "in the past." Clinicians may consider enquiring about PTSD in Latino patients who report feeling sad, anxious, nervous, or fearful. Our study suggests topics clinicians may include in the psychoeducation of patients with PTSD.

A Systematic Evaluation of Field-Based Screening Methods for the Assessment of Anterior Cruciate Ligament (ACL) Injury Risk.

PubMed

Fox, Aaron S; Bonacci, Jason; McLean, Scott G; Spittle, Michael; Saunders, Natalie

2016-05-01

Laboratory-based measures provide an accurate method to identify risk factors for anterior cruciate ligament (ACL) injury; however, these methods are generally prohibitive to the wider community. Screening methods that can be completed in a field or clinical setting may be more applicable for wider community use. Examination of field-based screening methods for ACL injury risk can aid in identifying the most applicable method(s) for use in these settings. The objective of this systematic review was to evaluate and compare field-based screening methods for ACL injury risk to determine their efficacy of use in wider community settings. An electronic database search was conducted on the SPORTDiscus™, MEDLINE, AMED and CINAHL databases (January 1990-July 2015) using a combination of relevant keywords. A secondary search of the same databases, using relevant keywords from identified screening methods, was also undertaken. Studies identified as potentially relevant were independently examined by two reviewers for inclusion. Where consensus could not be reached, a third reviewer was consulted. Original research articles that examined screening methods for ACL injury risk that could be undertaken outside of a laboratory setting were included for review. Two reviewers independently assessed the quality of included studies. Included studies were categorized according to the screening method they examined. A description of each screening method, and data pertaining to the ability to prospectively identify ACL injuries, validity and reliability, recommendations for identifying 'at-risk' athletes, equipment and training required to complete screening, time taken to screen athletes, and applicability of the screening method across sports and athletes were extracted from relevant studies. Of 1077 citations from the initial search, a total of 25 articles were identified as potentially relevant, with 12 meeting all inclusion/exclusion criteria. From the secondary search, eight further studies met all criteria, resulting in 20 studies being included for review. Five ACL-screening methods-the Landing Error Scoring System (LESS), Clinic-Based Algorithm, Observational Screening of Dynamic Knee Valgus (OSDKV), 2D-Cam Method, and Tuck Jump Assessment-were identified. There was limited evidence supporting the use of field-based screening methods in predicting ACL injuries across a range of populations. Differences relating to the equipment and time required to complete screening methods were identified. Only screening methods for ACL injury risk were included for review. Field-based screening methods developed for lower-limb injury risk in general may also incorporate, and be useful in, screening for ACL injury risk. Limited studies were available relating to the OSDKV and 2D-Cam Method. The LESS showed predictive validity in identifying ACL injuries, however only in a youth athlete population. The LESS also appears practical for community-wide use due to the minimal equipment and set-up/analysis time required. The Clinic-Based Algorithm may have predictive value for ACL injury risk as it identifies athletes who exhibit high frontal plane knee loads during a landing task, but requires extensive additional equipment and time, which may limit its application to wider community settings.

ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

PubMed Central

Negishi, Yuya; Mizobuchi, Kei; Urashima, Mitsuyoshi; Nakano, Tadashi

2017-01-01

Purpose To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS). Patients and Methods This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing. Results Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination. Conclusions We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population. PMID:28912966

Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing.

PubMed

Yanagawa, Takehiro; Kagara, Naofumi; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

2017-06-01

Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations. Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients. Functional analyses were then performed for the novel mutations we detected. We identified no mutations in primary tumors and six mutations in five recurrent tumors, including three types of known mutations (Y537C, Y537N, and D538G) and two novel mutations (E279V and G557R). We also identified seven mutations in five plasma samples, including three types of known mutations (S463P, Y537S, and D538G) and one mutation not reported in COSMIC database (L536H). All nine patients with ESR1 mutations were treated with aromatase inhibitors (AIs) prior to sampling, and the mutations were frequently detected in patients who received AI treatments in the metastatic setting. Among the three novel mutations (E279V, L536H, and G557R), L536H, but not E279V and G557R, showed ligand-independent activity. All three mutant proteins showed nuclear localization and had no relation with non-genomic ER pathways. Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

[Current Practice of Pre- and Postnatal Screening and Future Developments for Evidence Based Guidelines].

PubMed

Hebebrand, J; Hamelmann, E; Hartmann, A; Holtmann, M; Jöckel, K-H; Kremer, U; Legenbauer, T; Lücke, T; Radkowski, K; Reinehr, T; Wand, K; Mühlig, Y; Föcker, M

2017-01-01

Objectives: In this selective review we provide an overview of the current pre- and postnatal screenings up to 18 years established in Germany to inform physicians of different medical fields (gynecologists, pediatricians, general practitioners, other medical specialists who treat children, adolescents or pregnant females). Current State: Research on screening for different types of cancer has frequently failed to show any benefit. Thus, there is a need to broaden the evidence basis related to medical screenings especially for children and adolescents. Outlook: Potential future developments of pre- and postnatal screenings are illustrated including their social impact. The lack of an early detection of mental health problems is pointed out. An interdisciplinary collaboration and research is required to accumulate evidence with regard to medical screenings and to consider health economic and ethical aspects. © Georg Thieme Verlag KG Stuttgart · New York.

Differentially Private Frequent Subgraph Mining

PubMed Central

Xu, Shengzhi; Xiong, Li; Cheng, Xiang; Xiao, Ke

2016-01-01

Mining frequent subgraphs from a collection of input graphs is an important topic in data mining research. However, if the input graphs contain sensitive information, releasing frequent subgraphs may pose considerable threats to individual's privacy. In this paper, we study the problem of frequent subgraph mining (FGM) under the rigorous differential privacy model. We introduce a novel differentially private FGM algorithm, which is referred to as DFG. In this algorithm, we first privately identify frequent subgraphs from input graphs, and then compute the noisy support of each identified frequent subgraph. In particular, to privately identify frequent subgraphs, we present a frequent subgraph identification approach which can improve the utility of frequent subgraph identifications through candidates pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support derivation approach, where a series of methods has been proposed to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that our DFG algorithm satisfies ε-differential privacy. Extensive experimental results on real datasets show that the DFG algorithm can privately find frequent subgraphs with high data utility. PMID:27616876

Approaches to virtual screening and screening library selection.

PubMed

Wildman, Scott A

2013-01-01

The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

Using a discrete choice experiment to inform the design of programs to promote colon cancer screening for vulnerable populations in North Carolina.

PubMed

Pignone, Michael P; Crutchfield, Trisha M; Brown, Paul M; Hawley, Sarah T; Laping, Jane L; Lewis, Carmen L; Lich, Kristen Hassmiller; Richardson, Lisa C; Tangka, Florence Kl; Wheeler, Stephanie B

2014-11-30

Screening for colorectal cancer (CRC) is suboptimal, particularly for vulnerable populations. Effective intervention programs are needed to increase screening rates. We used a discrete choice experiment (DCE) to learn about how vulnerable individuals in North Carolina value different aspects of CRC screening programs. We enrolled English-speaking adults ages 50-75 at average risk of CRC from rural North Carolina communities with low rates of CRC screening, targeting those with public or no insurance and low incomes. Participants received basic information about CRC screening and potential program features, then completed a 16 task DCE and survey questions that examined preferences for four attributes of screening programs: testing options available; travel time required; money paid for screening or rewards for completing screening; and the portion of the cost of follow-up care paid out of pocket. We used Hierarchical Bayesian methods to calculate individual-level utilities for the 4 attributes' levels and individual-level attribute importance scores. For each individual, the attribute with the highest importance score was considered the most important attribute. Individual utilities were then aggregated to produce mean utilities for each attribute. We also compared DCE-based results with those from direct questions in a post-DCE survey. We enrolled 150 adults. Mean age was 57.8 (range 50-74); 55% were women; 76% White and 19% African-American; 87% annual household income under $30,000; and 51% were uninsured. Individuals preferred shorter travel; rewards or small copayments compared with large copayments; programs that included stool testing as an option; and greater coverage of follow-up costs. Follow-up cost coverage was most frequently found to be the most important attribute from the DCE (47%); followed by test reward/copayment (33%). From the survey, proportion of follow-up costs paid was most frequently cited as most important (42% of participants), followed by testing options (32%). There was moderate agreement (45%) in attribute importance between the DCE and the single question in the post-DCE survey. Screening test copayments and follow-up care coverage costs are important program characteristics in this vulnerable, rural population.

Screening and assessment of chronic pain among children with cerebral palsy: a process evaluation of a pain toolbox.

PubMed

Orava, Taryn; Provvidenza, Christine; Townley, Ashleigh; Kingsnorth, Shauna

2018-06-08

Though high numbers of children with cerebral palsy experience chronic pain, it remains under-recognized. This paper describes an evaluation of implementation supports and adoption of the Chronic Pain Assessment Toolbox for Children with Disabilities (the Toolbox) to enhance pain screening and assessment practices within a pediatric rehabilitation and complex continuing care hospital. A multicomponent knowledge translation strategy facilitated Toolbox adoption, inclusive of a clinical practice guideline, cerebral palsy practice points and assessment tools. Across the hospital, seven ambulatory care clinics with cerebral palsy caseloads participated in a staggered roll-out (Group 1: exclusive CP caseloads, March-December; Group 2: mixed diagnostic caseloads, August-December). Evaluation measures included client electronic medical record audit, document review and healthcare provider survey and interviews. A significant change in documentation of pain screening and assessment practice from pre-Toolbox (<2%) to post-Toolbox adoption (53%) was found. Uptake in Group 2 clinics lagged behind Group 1. Opportunities to use the Toolbox consistently (based on diagnostic caseload) and frequently (based on client appointments) were noted among contextual factors identified. Overall, the Toolbox was positively received and clinically useful. Findings affirm that the Toolbox, in conjunction with the application of integrated knowledge translation principles and an established knowledge translation framework, has potential to be a useful resource to enrich and standardize chronic pain screening and assessment practices among children with cerebral palsy. Implications for Rehabilitation It is important to engage healthcare providers in the conceptualization, development, implementation and evaluation of a knowledge-to-action best practice product. The Chronic Pain Toolbox for Children with Disabilities provides rehabilitation staff with guidance on pain screening and assessment best practice and offers a range of validated tools that can be incorporated in ambulatory clinic settings to meet varied client needs. Considering unique clinical contexts (i.e., opportunities for use, provider engagement, staffing absences/turnover) is required to optimize and sustain chronic pain screening and assessment practices in rehabilitation outpatient settings.

Hearing and vision screening tools for long-term care residents with dementia: protocol for a scoping review

PubMed Central

McGilton, Katherine S; Höbler, Fiona; Campos, Jennifer; Dupuis, Kate; Labreche, Tammy; Guthrie, Dawn M; Jarry, Jonathan; Singh, Gurjit; Wittich, Walter

2016-01-01

Introduction Hearing and vision loss among long-term care (LTC) residents with dementia frequently goes unnoticed and untreated. Despite negative consequences for these residents, there is little information available about their sensory abilities and care assessments and practices seldom take these abilities or accessibility needs into account. Without adequate knowledge regarding such sensory loss, it is difficult for LTC staff to determine the level of an individual's residual basic competence for communication and independent functioning. We will conduct a scoping review to identify the screening measures used in research and clinical contexts that test hearing and vision in adults aged over 65 years with dementia, aiming to: (1) provide an overview of hearing and vision screening in older adults with dementia; and (2) evaluate the sensibility of the screening tools. Methods and analysis This scoping review will be conducted using the framework by Arksey and O'Malley and furthered by methodological enhancements from cited researchers. We will conduct electronic database searches in CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We will also carry out a ‘grey literature’ search for studies or materials not formally published, both online and through interview discussions with healthcare professionals and research clinicians working in the field. Our aim is to find new and existing hearing and vision screening measures used in research and by clinical professionals of optometry and audiology. Abstracts will be independently reviewed twice for acceptance by a multidisciplinary team of researchers and research clinicians. Ethics and dissemination This review will inform health professionals working with this growing population. With the review findings, we aim to develop a toolkit and an algorithmic process to select the most appropriate hearing and vision screening assessments for LTC residents with dementia that will facilitate accurate testing and can inform care planning, thereby improving residents’ quality of life. PMID:27466242

Rapid polymerase chain reaction screening of Helicobacter pylori chromosomal point mutations.

PubMed

Ge, Z; Taylor, D E

1997-09-01

Microdiversity (within individual genes) in the genomes of different Helicobacter pylori strains has been demonstrated to be more frequent than that seen in other prokaryotes. Point mutations in some genes, such as the vacA and 23S ribosomal RNA genes could result in the alteration of pathogenicity or antibiotic susceptibility of individual H. pylori strains. Development of a simple, rapid, and reliable screening method would be useful in the molecular characterization of genetic variation among different H. pylori strains. The copP gene from H. pylori UA802 was used as a model for developing a mutation screening method. Four point mutations were introduced into the copP gene by in vitro site-directed mutagenesis and were verified by DNA sequencing. The mutated copP gene replaced the wild-type locus by natural transformation and homologous recombination. The site-specific mutants were screened by polymerase chain reaction (PCR) using 3'-end mismatched primers. The origins of the PCR fragments were demonstrated by Southern hybridization with the copP-derived DNA probe. Three of these four mutations were characterized by PCR with the specific primers that contained the 3'-terminal nucleotide complementary only to the mutated nucleotide on both plasmid and chromosomal DNA templates. One mutation was able to be identified with the foregoing primer containing an additional wild-type nucleotide at its 3'-end. Point mutant screening with these specific primers offers 100% sensitivity in the aforementioned conditions. To achieve optimal screening, the concentration of magnesium and the annealing temperature have to be adjusted. The procedure reported in this study is a simple, economical, rapid, and efficient approach in the identification of site-specific mutations on both plasmids and chromosomal DNA. Although the method was developed by using a specified H. pylori gene, it can be extended easily to other genes of interest in H. pylori or other organisms.

Hearing and vision screening tools for long-term care residents with dementia: protocol for a scoping review.

PubMed

McGilton, Katherine S; Höbler, Fiona; Campos, Jennifer; Dupuis, Kate; Labreche, Tammy; Guthrie, Dawn M; Jarry, Jonathan; Singh, Gurjit; Wittich, Walter

2016-07-26

Hearing and vision loss among long-term care (LTC) residents with dementia frequently goes unnoticed and untreated. Despite negative consequences for these residents, there is little information available about their sensory abilities and care assessments and practices seldom take these abilities or accessibility needs into account. Without adequate knowledge regarding such sensory loss, it is difficult for LTC staff to determine the level of an individual's residual basic competence for communication and independent functioning. We will conduct a scoping review to identify the screening measures used in research and clinical contexts that test hearing and vision in adults aged over 65 years with dementia, aiming to: (1) provide an overview of hearing and vision screening in older adults with dementia; and (2) evaluate the sensibility of the screening tools. This scoping review will be conducted using the framework by Arksey and O'Malley and furthered by methodological enhancements from cited researchers. We will conduct electronic database searches in CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We will also carry out a 'grey literature' search for studies or materials not formally published, both online and through interview discussions with healthcare professionals and research clinicians working in the field. Our aim is to find new and existing hearing and vision screening measures used in research and by clinical professionals of optometry and audiology. Abstracts will be independently reviewed twice for acceptance by a multidisciplinary team of researchers and research clinicians. This review will inform health professionals working with this growing population. With the review findings, we aim to develop a toolkit and an algorithmic process to select the most appropriate hearing and vision screening assessments for LTC residents with dementia that will facilitate accurate testing and can inform care planning, thereby improving residents' quality of life. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Development and Validation of a P-35S, T-nos, T-35S and P-FMV Tetraplex Real-time PCR Screening Method to Detect Regulatory Genes of Genetically Modified Organisms in Food.

PubMed

Eugster, Albert; Murmann, Petra; Kaenzig, Andre; Breitenmoser, Alda

2014-10-01

In routine analysis screening methods based on real-time PCR (polymerase chain reaction) are most commonly used for the detection of genetically modified (GM) plant material in food and feed. Screening tests are based on sequences frequently used for GM development, allowing the detection of a large number of GMOs (genetically modified organisms). Here, we describe the development and validation of a tetraplex real-time PCR screening assay comprising detection systems for the regulatory genes Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens nos terminator, Cauliflower Mosaic Virus 35S terminator and Figwort Mosaic Virus 34S promoter. Three of the four primer and probe combinations have already been published elsewhere, whereas primers and probe for the 35S terminator have been developed in-house. Adjustment of primer and probe concentrations revealed a high PCR sensitivity with insignificant physical cross-talk between the four detection channels. The sensitivity of each PCR-system is sufficient to detect a GMO concentration as low as 0.05% of the containing respective element. The specificity of the described tetraplex is high when tested on DNA from GM maize, soy, rapeseed and tomato. We also demonstrate the robustness of the system by inter-laboratory tests. In conclusion, this method provides a sensitive and reliable screening procedure for the detection of the most frequently used regulatory elements present in GM crops either authorised or unauthorised for food.

Convenient microtiter plate-based, oxygen-independent activity assays for flavin-dependent oxidoreductases based on different redox dyes

PubMed Central

Brugger, Dagmar; Krondorfer, Iris; Zahma, Kawah; Stoisser, Thomas; Bolivar, Juan M; Nidetzky, Bernd; Peterbauer, Clemens K; Haltrich, Dietmar

2014-01-01

Flavin-dependent oxidoreductases are increasingly recognized as important biocatalysts for various industrial applications. In order to identify novel activities and to improve these enzymes in engineering approaches, suitable screening methods are necessary. We developed novel microtiter-plate-based assays for flavin-dependent oxidases and dehydrogenases using redox dyes as electron acceptors for these enzymes. 2,6-dichlorophenol-indophenol, methylene green, and thionine show absorption changes between their oxidized and reduced forms in the visible range, making it easy to judge visually changes in activity. A sample set of enzymes containing both flavoprotein oxidases and dehydrogenases – pyranose 2-oxidase, pyranose dehydrogenase, cellobiose dehydrogenase, d-amino acid oxidase, and l-lactate oxidase – was selected. Assays for these enzymes are based on a direct enzymatic reduction of the redox dyes and not on the coupled detection of a reaction product as in the frequently used assays based on hydrogen peroxide formation. The different flavoproteins show low Michaelis constants with these electron acceptor substrates, and therefore these dyes need to be added in only low concentrations to assure substrate saturation. In conclusion, these electron acceptors are useful in selective, reliable and cheap MTP-based screening assays for a range of flavin-dependent oxidoreductases, and offer a robust method for library screening, which could find applications in enzyme engineering programs. PMID:24376171

Quantitative Tagless Copurification: A Method to Validate and Identify Protein-Protein Interactions

DOE PAGES

Shatsky, Maxim; Dong, Ming; Liu, Haichuan; ...

2016-04-20

Identifying protein-protein interactions (PPIs) at an acceptable false discovery rate (FDR) is challenging. Previously we identified several hundred PPIs from affinity purification - mass spectrometry (AP-MS) data for the bacteria Escherichia coli and Desulfovibrio vulgaris. These two interactomes have lower FDRs than any of the nine interactomes proposed previously for bacteria and are more enriched in PPIs validated by other data than the nine earlier interactomes. To more thoroughly determine the accuracy of ours or other interactomes and to discover further PPIs de novo, here we present a quantitative tagless method that employs iTRAQ MS to measure the copurification ofmore » endogenous proteins through orthogonal chromatography steps. 5273 fractions from a four-step fractionation of a D. vulgaris protein extract were assayed, resulting in the detection of 1242 proteins. Protein partners from our D. vulgaris and E. coli AP-MS interactomes copurify as frequently as pairs belonging to three benchmark data sets of well-characterized PPIs. In contrast, the protein pairs from the nine other bacterial interactomes copurify two- to 20-fold less often. We also identify 200 high confidence D. vulgaris PPIs based on tagless copurification and colocalization in the genome. These PPIs are as strongly validated by other data as our AP-MS interactomes and overlap with our AP-MS interactome for D.vulgaris within 3% of expectation, once FDRs and false negative rates are taken into account. Finally, we reanalyzed data from two quantitative tagless screens of human cell extracts. We estimate that the novel PPIs reported in these studies have an FDR of at least 85% and find that less than 7% of the novel PPIs identified in each screen overlap. Our results establish that a quantitative tagless method can be used to validate and identify PPIs, but that such data must be analyzed carefully to minimize the FDR.« less

Targeting imported malaria through social networks: a potential strategy for malaria elimination in Swaziland.

PubMed

Koita, Kadiatou; Novotny, Joseph; Kunene, Simon; Zulu, Zulizile; Ntshalintshali, Nyasatu; Gandhi, Monica; Gosling, Roland

2013-06-27

Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland's eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to identify and treat additional malaria cases. Implementation of a proactive screening programme of importation networks may help Swaziland halt transmission and achieve malaria elimination by 2015.

Quantitative Tagless Copurification: A Method to Validate and Identify Protein-Protein Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shatsky, Maxim; Dong, Ming; Liu, Haichuan

Identifying protein-protein interactions (PPIs) at an acceptable false discovery rate (FDR) is challenging. Previously we identified several hundred PPIs from affinity purification - mass spectrometry (AP-MS) data for the bacteria Escherichia coli and Desulfovibrio vulgaris. These two interactomes have lower FDRs than any of the nine interactomes proposed previously for bacteria and are more enriched in PPIs validated by other data than the nine earlier interactomes. To more thoroughly determine the accuracy of ours or other interactomes and to discover further PPIs de novo, here we present a quantitative tagless method that employs iTRAQ MS to measure the copurification ofmore » endogenous proteins through orthogonal chromatography steps. 5273 fractions from a four-step fractionation of a D. vulgaris protein extract were assayed, resulting in the detection of 1242 proteins. Protein partners from our D. vulgaris and E. coli AP-MS interactomes copurify as frequently as pairs belonging to three benchmark data sets of well-characterized PPIs. In contrast, the protein pairs from the nine other bacterial interactomes copurify two- to 20-fold less often. We also identify 200 high confidence D. vulgaris PPIs based on tagless copurification and colocalization in the genome. These PPIs are as strongly validated by other data as our AP-MS interactomes and overlap with our AP-MS interactome for D.vulgaris within 3% of expectation, once FDRs and false negative rates are taken into account. Finally, we reanalyzed data from two quantitative tagless screens of human cell extracts. We estimate that the novel PPIs reported in these studies have an FDR of at least 85% and find that less than 7% of the novel PPIs identified in each screen overlap. Our results establish that a quantitative tagless method can be used to validate and identify PPIs, but that such data must be analyzed carefully to minimize the FDR.« less

Prevalence of Multidrug-Resistant Organisms in Hospitalized Pediatric Refugees in an University Children's Hospital in Germany 2015-2016.

PubMed

Tenenbaum, Tobias; Becker, Klaus-Peter; Lange, Bettina; Martin, Anka; Schäfer, Peter; Weichert, Stefan; Schroten, Horst

2016-11-01

OBJECTIVE To determine the prevalence of multidrug-resistant organisms (MDROs) colonizing in pediatric refugees admitted to a University Children Hospital in Germany. DESIGN Retrospective observational study. SETTING General pediatric and pediatric surgery units. PATIENTS In Germany, recommendations for MDRO screening of pediatric refugees were recently published. According to these and institutional recommendations, all hospitalized pediatric refugees were screened for MDROs between October 2015 and March 2016. METHODS Using electronic surveillance data, we performed a chart review to identify the prevalence of MDROs among and the clinical diagnoses of pediatric refugees. RESULTS Among 325 patients hospitalized for various causes, most frequently gastroenteritis (30.9%), MDROs were detected in 33.8%. Most of these patients were colonized with multidrug-resistant Gram-negative (MRGN) bacteria (113 isolates), mostly 2MRGN/ESBL (87 isolates); some patients were colonized with methicillin-resistant Staphylococcus aureus (MRSA, 22 isolates); and 1 patient was colonized with vancomycin-resistant enterococci (VRE). Among 110 refugee patients, we detected single colonization with an MDRO in 84 patients (76.4%), co-colonization with 2 pathogens in 23 patients (20.9%), and triple colonization in 3 patients (2.7%). However, infections with MDROs occurred in only 3.6% of pediatric refugees. The peak of positive MDRO screening results in 2015 correlated with an increased hospitalization rate. CONCLUSION Implementation of infection control measures among pediatric refugees is challenging. Due to the high frequency of MDROs in these patients, current screening, isolation, and treatment strategies may have to be adapted. Infect Control Hosp Epidemiol 2016;1-5.

Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013-2015.

PubMed

Deng, Kui; He, Chunhua; Zhu, Jun; Liang, Juan; Li, Xiaohong; Xie, Xiaoyan; Yu, Ping; Li, Nana; Li, Qi; Wang, Yanping

2018-06-27

Congenital hypothyroidism (CH) is one of the most frequent, preventable causes of mental retardation. Little has been reported on the epidemiological characteristics of CH in China. We aimed to estimate the incidence of CH in China and investigate its geographical variation. We analyzed data from the nationwide newborn screening program for CH between 2013 and 2015. Poisson regression was used to generate the odds ratios (ORs) and 95% confidence intervals (CIs) between the rates of CH and selected demographic characteristics and assess the potential association between CH incidence and geographical locations. A total of 18,666 patients with CH were identified from 45.2 million newborns, yielding an overall incidence rate of 4.13 per 10,000 live births. Compared with those in the remote area, regardless of infant sex, a higher incidence risk for CH was present in newborns in coastal areas and inland areas (females: OR=2.00, 95% CI: 1.86-2.16 and OR=1.74, 95% CI: 1.61-1.87, respectively; males: OR=1.70, 95% CI: 1.59-1.83 and OR=1.52, 95% CI: 1.42-1.63, respectively). Additionally, the highest risk of CH for thyroid-stimulating hormone (TSH) screening values <40 mU/L was observed among neonates in the coastal areas, while TSH screening values of 70-100 mU/L were observed among those in the inland areas. The overall incidence of CH is high in China. The significant geographical variations of CH incidence are presented in this study.

Prevalence of complementary and alternative therapy use by cancer patients undergoing radiation therapy.

PubMed

Edwards, Grace V; Aherne, Noel J; Horsley, Patrick J; Benjamin, Linus C; McLachlan, Craig S; McKay, Michael J; Shakespeare, Thomas P

2014-12-01

The use of complementary and alternative therapies (CAT) in oncology patients is increasing in incidence, with calls to routinely screen for their use. We introduced a screening tool as part of clinical care to identify CAT use. We evaluated all patients who attended the radiation oncology outpatient clinic between December 2011 and July 2012, who had filled out the CAT screening tool, and evaluated types of CAT use, reasons for use and predictors of CAT usage. A total of 639 patients completed the CAT screening tool, which was 75% of eligible patients. There were 464 (72.6%) men and 175 (27.4%) women, with a mean age of 69.9 years (range 27-94 years). Prostate cancer was the predominant diagnosis (53.1%), followed by breast cancer (17.5%) and skin cancer (14.7%). Of these, 530 patients (82.9%) had used at least one therapy. Of the 530 patients using CAT, the most quoted reasons for use were to improve quality of life (42.6%), to boost the immune system and general health (33.6%), to increase energy levels (32.6%) and to live longer (28.9%). Of the 530 users, only 112 patients (21.1%) took CAT to help cure their cancer. Women were significantly more likely to use CAT, as were patients with breast cancer. The use of CAT in patients with cancer is prevalent and more frequent in our population than in other published studies. Few patients use CAT to improve their cancer cure, but rather use CAT for other reasons. © 2014 Wiley Publishing Asia Pty Ltd.

Low Rates of Dermatologic Care and Skin Cancer Screening Among Inflammatory Bowel Disease Patients.

PubMed

Anderson, Alyce; Ferris, Laura K; Click, Benjamin; Ramos-Rivers, Claudia; Koutroubakis, Ioannis E; Hashash, Jana G; Dunn, Michael; Barrie, Arthur; Schwartz, Marc; Regueiro, Miguel; Binion, David G

2018-04-30

Dermatologic manifestations of inflammatory bowel disease (IBD) are common, and certain IBD medications increase the risk of skin cancer. To define the rates of care and factors associated with dermatologic utilization with a focus on skin cancer screening. We utilized a prospective, natural history IBD research registry to evaluate all outpatient healthcare encounters from 2010 to 2016. Gastrointestinal, dermatologic and primary care visits per individual were identified. We calculated the proportion of patients obtaining care, categorized primary indications for dermatologic visits, determined the incidence of melanoma and non-melanoma skin cancers, and used logistic regression to determine factors associated with dermatology utilization. Of the 2127 IBD patients included, 452 (21.3%) utilized dermatology over the study period, and 55 (2.6%) had a total body skin examination at least once. The 452 patients incurred 1633 dermatology clinic visits, 278 dermatologic procedures, and 1108 dermatology telephone encounters. The most frequent indication was contact dermatitis or dermatitis. Factors associated with dermatology use were family history of skin cancer, employment, systemic steroids, longer disease duration, emergency room use, and the number of IBD-related clinic visits. Between 8.3 and 11% of IBD patients recommended for skin cancer screening visited dermatology each year, and the resulting incidence of non-melanoma skin cancer was 35.4/10,000 [95% CI 23.3-51.5] and melanoma was 6.56/10,000 [95% CI 2.1-15.3]. Less than one in ten IBD patients obtain dermatologic care. Given the increased risk of skin cancers among IBD patients, an emphasis on education, prevention, and screening merits attention.

Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, in Thyroid Cancers of Young Patients in Fukushima.

PubMed

Iyama, Keita; Matsuse, Michiko; Mitsutake, Norisato; Rogounovitch, Tatiana; Saenko, Vladimir; Suzuki, Keiji; Ashizawa, Mai; Ookouchi, Chiyo; Suzuki, Satoshi; Mizunuma, Hiroshi; Fukushima, Toshihiko; Suzuki, Shinichi; Yamashita, Shunichi

2017-06-01

The BRAF V600E mutation is the most frequent genetic abnormality in adult papillary thyroid carcinomas (PTCs). On the other hand, various chromosomal rearrangements are more prevalent in childhood and adolescent PTCs. The aim of the present study was to identify novel rearrangements in PTCs from young patients. Among 63 postoperative specimens of childhood and adolescent PTCs, which had been discovered by the thyroid ultrasound screening program in Fukushima, nine samples without prevalent known oncogenes, BRAF V600E , RAS, RET/PTC1, RET/PTC3, and ETV6/NTRK3, were analyzed in the current study by quantitative real-time reverse transcription polymerase chain reaction to screen for novel fusion genes by comparing transcript expression between extracellular and kinase domains of ALK, NTRK1, NTRK3, and RET. Of the above nine samples, five samples were suspected to harbor a fusion, and using subsequent 5' rapid amplification of cDNA end (RACE), two already reported fusion oncogenes, STRN/ALK and TPR/NTRK1, and three novel fusions, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, were identified. Functional analyses of these three chimeric genes were performed, and their transforming abilities were confirmed through the activation of mitogen-activated protein kinase (MAPK). Three novel fusion oncogenes have been identified in young PTC patients in Fukushima, suggesting that rare fusions may be present among the cases negative for known oncogenes in this age group and that such rearrangements can play a significant role in thyroid carcinogenesis.

Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization.

PubMed

Ramirez, Ursula D; Nikonova, Anna S; Liu, Hanqing; Pecherskaya, Anna; Lawrence, Sarah H; Serebriiskii, Ilya G; Zhou, Yan; Robinson, Matthew K; Einarson, Margret B; Golemis, Erica A; Jaffe, Eileen K

2015-05-28

Overexpression or mutation of the epidermal growth factor receptor (EGFR) potently enhances the growth of many solid tumors. Tumor cells frequently display resistance to mechanistically-distinct EGFR-directed therapeutic agents, making it valuable to develop therapeutics that work by additional mechanisms. Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain. Recent studies have identified a novel prone extracellular tetrameric EGFR configuration, which we identify as a potential target for drug discovery. Our focus is on the prone EGFR tetramer, which contains a novel protein-protein interface involving extracellular domain III. This EGFR tetramer is computationally targeted for stabilization by small molecule ligand binding. This study performed virtual screening of a Life Chemicals, Inc. small molecule library of 345,232 drug-like compounds against a molecular dynamics simulation of protein-protein interfaces distinct to the novel tetramer. One hundred nine chemically diverse candidate molecules were selected and evaluated using a cell-based high-content imaging screen that directly assessed induced internalization of the EGFR effector protein Grb2. Positive hits were further evaluated for influence on phosphorylation of EGFR and its effector ERK1/2. Fourteen hit compounds affected internalization of Grb2, an adaptor responsive to EGFR activation. Most hits had limited effect on cell viability, and minimally influenced EGFR and ERK1/2 phosphorylation. Docked hit compound poses generally include Arg270 or neighboring residues, which are also involved in binding the effective therapeutic cetuximab, guiding further chemical optimization. These data suggest that the EGFR tetrameric configuration offers a novel cancer drug target.

A systematic review of the factors that influence the quality and effectiveness of telesupervision for health professionals.

PubMed

Martin, Priya; Lizarondo, Lucylynn; Kumar, Saravana

2018-05-01

Introduction Whilst telesupervision (clinical supervision undertaken using communication technology) is being used more frequently, there is limited information on what factors influence its effectiveness and quality. We undertook this systematic review to address this gap. Methods Eligible telesupervision studies were identified following targeted search of electronic databases and the grey literature. Data were synthesised thematically, resulting in development of core themes. Results We identified 286 papers for initial relevancy screening by title and abstract. The full text of 36 papers were then retrieved and assessed for further relevance. A total of 11 papers were included in the final analysis. We identified eight themes that contribute to effective and high-quality telesupervision: supervisee characteristics, supervisor characteristics, supervision characteristics, supervisory relationship, communication strategies, prior face-to-face contact, environmental factors and technological considerations. Conclusion From the available evidence, telesupervision can be a feasible and acceptable form of clinical supervision if set up well. Further studies with robust designs are required to strengthen the existing evidence on what makes telesupervision effective, as well as to examine its cost-effectiveness.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

PubMed Central

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel G.

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology towards a long-term cure for type I diabetes. PMID:23660251

Understanding Positive Play: An Exploration of Playing Experiences and Responsible Gambling Practices.

PubMed

Wood, Richard T A; Griffiths, Mark D

2015-12-01

This study is one of the first to explore in detail the behaviors, attitudes and motivations of players that show no signs of at-risk or problem gambling behavior (so-called 'positive players'). Via an online survey, 1484 positive players were compared with 209 problem players identified using the Lie/Bet screen. The study identified two distinct groups of positive players defined according to their motivations to play and their engagement with responsible gambling (RG) practices. Those positive players that played most frequently employed the most personal RG strategies. Reasons that positive players gave for gambling were focused on leisure (e.g., playing for fun, being entertained, and/or winning a prize). By contrast, problem gamblers were much more focused upon modifying mood states (e.g., excitement, relaxation, depression and playing when bored or upset). The present study also suggests that online gambling is not, by default, inherently riskier than gambling in more traditional ways, as online gambling was the most popular media by which positive players gambled. Furthermore, most positive players reported that it was easier to stick to their limits when playing the National Lottery online compared to traditional retail purchasing of tickets. Problem players were significantly more likely than positive players to gamble with family and friends, suggesting that, contrary to a popular RG message, social play may not be inherently safer than gambling alone. It is proposed that players (generally) may identify more with the term 'positive play' than the term 'RG' which is frequently interpreted as being aimed at people with gambling problems, rather than all players.

Prevalence of tics in schoolchildren in central Spain: a population-based study.

PubMed

Cubo, Esther; Gabriel y Galán, José María Trejo; Villaverde, Vanesa Ausín; Velasco, Sara Sáez; Benito, Vanesa Delgado; Macarrón, Jesús Vicente; Guevara, José Cordero; Louis, Elan D; Benito-León, Julián

2011-08-01

Tic disorders constitute a neurodevelopmental disorder of childhood. This study sought to determine the prevalence of tic disorders in a school-based sample. A randomized sample of 1158 schoolchildren, based on clusters (classrooms) in the province of Burgos (Spain), was identified on a stratified sampling frame combining types of educational center and setting (mainstream schools and special education), using a two-phase approach (screening and diagnosis ascertainment by a neurologist). Tics with/without impairment criterion were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders criteria. In mainstream schools, tics were observed in 125/741 students (16.86%; 95% confidence interval, 14.10-19.63), and were more frequent in boys (87/448, 19.42%; 95% confidence interval, 15.64-23.19) compared with girls (38/293, 12.96%; 95% confidence interval, 8.95-16.98; P = 0.03). In special education centers, tics disorders were observed in 11/54 of children (20.37%; 95% confidence interval, 8.70-32.03). Overall, tics with impairment criteria were less frequent than tics without impairment criteria (4.65% vs 11.85%, P < 0.0001). The most frequent diagnoses involved chronic motor tics (6.07%) and Tourette syndrome (5.26%). Tic disorders are common in childhood, and the use or nonuse of impairment criteria exerts a significant impact on tic prevalence estimates. Copyright © 2011 Elsevier Inc. All rights reserved.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

PubMed

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

Psychiatric comorbidity among patients with hypochondriasis.

PubMed

Noyes, R; Kathol, R G; Fisher, M M; Phillips, B M; Suelzer, M T; Woodman, C L

1994-03-01

The purpose of this study was to determine the nature and extent of comorbidity among patients with DSM-III-R hypochondriasis and to examine the relationships between this disorder and coexisting psychiatric illness. For this purpose, patients seen in a general medicine clinic were screened using measures of hypochondriacal attitudes and somatic symptoms. Those scoring above an established cutoff were given a structured diagnostic interview. In this manner, 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were identified. The presence of other psychiatric disorders (current and past) was determined by means of the same diagnostic interview. More hypochondriacal subjects (62.0%) had lifetime comorbidity than did controls (30.0%). Major depression, the most frequent comorbid disturbance, was usually current and most often had an onset after that of hypochondriasis. Panic disorder with agoraphobia, the most frequent anxiety disorder, was also current but often began before or at the same time as hypochondriasis. Few subjects met criteria for somatization disorder but a third qualified for a subsyndromal form of this disorder. The data show that, in medical outpatients with hypochondriasis, mood and anxiety disorders frequently coexist. This comorbidity is subject to varying interpretations including overlap of symptom criteria, treatment-seeking bias, and the possibility that hypochondriasis predisposes to or causes the comorbid disorder, as seems likely in the case of depression. In some instances hypochondriasis may be an associated feature of another illness.

Mobile medical image retrieval

NASA Astrophysics Data System (ADS)

Duc, Samuel; Depeursinge, Adrien; Eggel, Ivan; Müller, Henning

2011-03-01

Images are an integral part of medical practice for diagnosis, treatment planning and teaching. Image retrieval has gained in importance mainly as a research domain over the past 20 years. Both textual and visual retrieval of images are essential. In the process of mobile devices becoming reliable and having a functionality equaling that of formerly desktop clients, mobile computing has gained ground and many applications have been explored. This creates a new field of mobile information search & access and in this context images can play an important role as they often allow understanding complex scenarios much quicker and easier than free text. Mobile information retrieval in general has skyrocketed over the past year with many new applications and tools being developed and all sorts of interfaces being adapted to mobile clients. This article describes constraints of an information retrieval system including visual and textual information retrieval from the medical literature of BioMedCentral and of the RSNA journals Radiology and Radiographics. Solutions for mobile data access with an example on an iPhone in a web-based environment are presented as iPhones are frequently used and the operating system is bound to become the most frequent smartphone operating system in 2011. A web-based scenario was chosen to allow for a use by other smart phone platforms such as Android as well. Constraints of small screens and navigation with touch screens are taken into account in the development of the application. A hybrid choice had to be taken to allow for taking pictures with the cell phone camera and upload them for visual similarity search as most producers of smart phones block this functionality to web applications. Mobile information access and in particular access to images can be surprisingly efficient and effective on smaller screens. Images can be read on screen much faster and relevance of documents can be identified quickly through the use of images contained in the text. Problems with the many, often incompatible mobile platforms were discovered and are listed in the text. Mobile information access is a quickly growing domain and the constraints of mobile access also need to be taken into account for image retrieval. The demonstrated access to the medical literature is most relevant as the medical literature and their images are clearly the largest knowledge source in the medical field.

Improving clinical cognitive testing: report of the AAN Behavioral Neurology Section Workgroup.

PubMed

Daffner, Kirk R; Gale, Seth A; Barrett, A M; Boeve, Bradley F; Chatterjee, Anjan; Coslett, H Branch; D'Esposito, Mark; Finney, Glen R; Gitelman, Darren R; Hart, John J; Lerner, Alan J; Meador, Kimford J; Pietras, Alison C; Voeller, Kytja S; Kaufer, Daniel I

2015-09-08

To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment. © 2015 American Academy of Neurology.

Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

PubMed

Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

2017-11-01

The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

Anxiety During Pregnancy and Postpartum

MedlinePlus

... Traumatic Stress Disorder Bipolar Mood Disorders Postpartum Psychosis Social Support Online Training Help for Moms Frequently Asked Questions ... 944.4773 Learn More Pregnancy & Postpartum Mental Health Social Support Online Training Screening Recommendations Depression During Pregnancy & Postpartum ...

School Health Screening of Indochinese Refugee Children.

ERIC Educational Resources Information Center

Pickwell, Sheila M.

1981-01-01

Indochinese children registering for the first time in American schools are appearing with multiple health problems. These frequently include lice and scabies, intestinal parasites, vision and hearing defects, and severe dental decay. (JN)

Screening for autism identifies behavioral disorders in children functional defecation disorders.

PubMed

Kuizenga-Wessel, Sophie; Di Lorenzo, Carlo; Nicholson, Lisa M; Butter, Eric M; Ratliff-Schaub, Karen L; Benninga, Marc A; Williams, Kent C

2016-10-01

This study prospectively assessed whether positive screening surveys for autism spectrum disorders (ASDs) in children with functional defecation disorders (FDDs) accurately identify ASD. Parents of children (4-12 years) who met Rome III criteria for functional constipation (FC), FC with fecal incontinence (FI) and functional nonretentive FI (FNRFI) completed two ASD screening surveys. Children with positive screens were referred for psychological evaluation, and a year later, follow-up surveys were conducted. Of the 97 study participants, 30.9 % were diagnosed with FC, 62.9 % with FC with FI, and 6.2 % with FNRFI. ASD surveys were positive for 27 children (27.8 %). New DSM diagnoses were made in 10 out of the 15 children that completed further evaluation. Two (2.1 %) met criteria for ASD, and 12 (12.4 %) met criteria for other behavioral disorders. Average SRS and SCQ-L scores were higher in subjects with FC with FI as compared to FC alone and in those who reported no improvement versus those who reported improvement 1 year later. While positive ASD screening surveys did not correctly identify ASD in the majority, it did help to identify other unrecognized behavioral disorders in children with FDD. High screening scores were more common in children with FC with FI and in children with poorer responses to current medical treatments. •A prior study found that 29 % of children with FDD scored positive on ASD screening questionnaires. •Whether positive screens correctly identify ASD in children with FDD is unknown. What is New: •This study shows that positive ASD screens do not correctly identify ASD in children with FDD. However, the use of ASD screening questionnaires can identify previously unrecognized and untreated behavioral/developmental disorders in children with FDD. •High screening scores are more common in children with FC with FI and in children with poorer responses to current medical treatments.

Identifying Nursing Interventions in a Cancer Screening Program Using Nursing Interventions Classification Taxonomy.

PubMed

Benito, Llucia; Lluch, María Teresa; Falcó, Anna Marta; García, Montse; Puig, Montse

2017-04-01

This study aimed to investigate which Nursing Interventions Classification (NIC) labels correspond to specific nursing interventions provided during cancer screening to establish a nursing documentation system. This descriptive study was conducted to identify and classify the interventions that cancer screening nurses perform based on an initial list. The initial list was grouped into 15 interventions that corresponded to four domains and eight classes. The study found expert consensus regarding the duties of cancer screening nurses and identified 15 interventions that should be implemented in clinical practice for cancer screening care, according to the NIC taxonomy. This study is the first step in developing indicators to assess nursing performance in cancer screening, and it helps to establish the core competency requirements for cancer screening nurses. © 2015 NANDA International, Inc.

Validation of the Edinburgh Postnatal Depression Scale (EPDS) on the Thai–Myanmar border

PubMed Central

Ing, Harriet; Fellmeth, Gracia; White, Jitrachote; Stein, Alan; Simpson, Julie A; McGready, Rose

2017-01-01

Postnatal depression is common and may have severe consequences for women and their children. Locally validated screening tools are required to identify at-risk women in marginalised populations. The Edinburgh Postnatal Depression Scale (EPDS) is one of the most frequently used tools globally. This cross-sectional study assessed the validity and acceptability of the EPDS in Karen and Burmese among postpartum migrant and refugee women on the Thai–Myanmar border. The EPDS was administered to participants and results compared with a diagnostic interview. Local staff provided feedback on the acceptability of the EPDS through a focus group discussion. Results from 670 women showed high accuracy and reasonable internal consistency of the EPDS. However, acceptability to local staff was low, limiting the utility of the EPDS in this setting despite its good psychometrics. Further work is required to identify a tool that is acceptable and sensitive to cultural manifestations of depression in this vulnerable population. PMID:28699396

Bullying and Victimization Among Children

PubMed Central

Shetgiri, Rashmi

2013-01-01

Bullying among children is a significant public health problem world-wide. Bullying is most commonly defined as repeated, intentional aggression, perpetrated by a more powerful individual or group against a less powerful victim. Trends in victimization and moderate to frequent bullying may be decreasing slightly in the United States, but over 20% of children continue to be involved in bullying. Direct bullying consists of physical and verbal aggression, whereas indirect bullying involves relational aggression. Cyber bullying is an emerging problem which may be more difficult to identify and intervene with than traditional bullying. Bullies, victims, and bully-victims are at risk for negative short and long-term consequences such as depression, anxiety, low self-esteem, and delinquency. Various individual, parental, and peer factors increase the risk for involvement in bullying. Anti-bullying interventions are predominantly school-based and demonstrate variable results. Healthcare providers can intervene in bullying by identifying potential bullies or victims, screening them for co-morbidities, providing counseling and resources, and advocating for bullying prevention. PMID:24007839

STRUCTURE OF THE UNIVERSITY PERSONALITY INVENTORY FOR CHINESE COLLEGE STUDENTS.

PubMed

Zhang, Jieting; Lanza, Stephanie; Zhang, Minqiang; Su, Binyuan

2015-06-01

The University Personality Inventory, a mental health instrument for college students, is frequently used for screening in China. However, its unidimensionality has been questioned. This study examined its dimensions to provide more information about the specific mental problems for students at risk. Four subsamples were randomly created from a sample (N = 6,110; M age = 19.1 yr.) of students at a university in China. Principal component analysis with Promax rotation was applied on the first two subsamples to explore dimension of the inventory. Confirmatory factor analysis was conducted on the third subsample to verify the exploratory dimensions. Finally, the identified factors were compared to the Symptom Checklist-90 (SCL-90) to support validity, and sex differences were examined, based on the fourth subsample. Five factors were identified: Physical Symptoms, Cognitive Symptoms, Emotional Vulnerability, Social Avoidance, and Interpersonal Sensitivity, accounting for 60.3% of the variance. All the five factors were significantly correlated with the SCL-90. Women scored significantly higher than men on Cognitive Symptoms and Interpersonal Sensitivity.

WT1: a weak spot in KRAS-induced transformation

PubMed Central

Licciulli, Silvia; Kissil, Joseph L.

2010-01-01

Activating mutations in the Ras alleles are found frequently in tumors, making the proteins they encode highly attractive candidate therapeutic targets. However, Ras proteins have proven difficult to target directly. Recent approaches have therefore focused on identifying indirect targets to inhibit Ras-induced oncogenesis. For example, RNAi-based negative selection screens to identify genes that when silenced in concert with activating Ras mutations are incompatible with cellular proliferation, a concept known as synthetic lethality. In this issue of the JCI, Vicent et al. report on the identification of Wilms tumor 1 (Wt1) as a Kras synthetic-lethal gene in a mouse model of lung adenocarcinoma. Silencing of Wt1 in cells expressing an endogenous allele of activated Kras triggers senescence in vitro and has an impact on tumor progression in vivo. These findings are of significant interest given previous studies suggesting that the ability of oncogenic Kras to induce senescence versus proliferation depends on its levels of expression. PMID:20972324

Integrated management of major depression for people with cancer.

PubMed

Walker, Jane; Sharpe, Michael

2014-12-01

Major depression is an important complication of cancer. However, it is frequently inadequately treated. There are challenges both in identifying which cancer patients are depressed, and in ensuring that these patients receive effective treatment for their depression. Integration of depression management into cancer care has been advocated as a way to address these challenges. Such integrated approaches must include both the systematic identification of cases and the delivery of treatment. We describe here a system of depression care that includes both a screening programme to identify patients with depression and a linked treatment programme, based on the collaborative care model, called 'Depression Care for People with Cancer' (DCPC). The system of care was designed to be fully integrated with specialist cancer services and has been robustly evaluated in randomized trials. We describe how the system operates and explain why it is designed as it is. We also summarize the evidence for its effectiveness and cost-effectiveness and discuss its implementation in routine clinical practice.

[Adolescents and new technologies: Behaviours pointing a possible addiction problem].

PubMed

Labrador Encinas, Francisco Javier; Villadangos González, Silvia María

2010-05-01

The aim of this work is to evaluate adolescents' subjective risk perception derived from the use of the New Technologies (NT), and to identify behaviours or warning symptoms of possible addiction problems. A sample of 1,710 underage students of Madrid responded to the DENA questionnaire. Firstly, we found a positive correlation between the time of NT use and the perception of addiction problems. Also, age was positively correlated to these perception problems. Secondly, the results indicated that television is the technology that generates a major perception problem in underage students. Lastly, the NTs have produced behaviours that are similar to those produced by other established addictions. Among them are notable the relaxation caused by their use or discomfort if they cannot be used. In addition, the frequent presence of other behaviours exclusive to these instruments has been identified, such as constantly checking one's mobile phone screen. It is necessary to continue studying possible addictive behaviours specific to the NT.

Nuclear localisation and epigenetic inactivation of the ras effector/tumour suppressor RASSF2A in multiple human cancers

PubMed Central

Cooper, Wendy N.; Dickinson, Rachel E.; Dallol, Ashraf; Grigorieva, Elvira V.; Pavlova, Tatiana V.; Hesson, Luke B.; Bieche, Ivan; Broggini, Massimo; Maher, Eamonn R; Zabarovsky, Eugene R.; Clark, Geoffrey J; Latif, Farida

2010-01-01

RASSF2 is a recently identified member of a class of novel tumour suppressor genes, all containing a ras association domain. We previously demonstrated that the A isoform of RASSF2, is frequently inactivated by promoter region hypermethylation in colorectal tumours and adenomas, methylation was tumour specific and that expression in methylated tumour lines could be reactivated by treatment with 5-aza-2dc. RASSF2 resides at 20p13, this region has been demonstrated to be frequently lost in human cancers. In this report we investigated methylation status of the RASSF2A promoter CpG island in a series of breast, ovarian and non-small cell lung cancers (NSCLC). RASSF2A was frequently methylated in breast tumour cell lines 65% (13/20) and in primary breast tumours 38% (15/40). RASSF2A gene expression could be switched back on in methylated breast tumour cell lines after treatment with 5-aza-2dC, whilst unmethylated lines showed no difference in level of expression before and after 5-aza-2dC treatment. RASSF2A was also frequently methylated in NSCLC tumours 44% (22/50). Methylation in breast tumours and NSCLC was tumour specific. We did not detect RASSF2A methylation in ovarian tumours (0/17). Furthermore no mutations were found in the coding region of RASSF2A in these ovarian tumours. RASSF2A suppressed breast tumour cell growth in vitro (through colony formation and soft agar assays) and in vivo. We identified a highly conserved putative bipartite nuclear localisation signal (NLS) between amino acids 151 and 167 in the RASSF2A sequence and demonstrated that endogenous RASSF2A localised to the nucleus. Mutation of the putative nuclear localisation signal abolished the nuclear localisation so RASSF2A became predominantly cytoplasmic. Our data indicates that RASSF2A is frequently methylated in colorectal, breast and NSCLC tumours, furthermore, the methylation is tumour specific. Hence we have identified RASSF2A as a novel methylation marker for multiple malignancies and it has the potential to be developed into a valuable marker for screening several cancers in parallel using promoter hypermethylation profiles. We also demonstrate that RASSF2 has a functional NLS signal. Furthermore this is the first report demonstrating that RASSF2 suppresses growth of cancer cells in vivo. Hence providing further evidence for its role as a tumour suppressor gene located at 20p13. PMID:17891178

Screening for Intimate Partner Violence in Orthopedic Patients: A Comparison of Three Screening Tools

ERIC Educational Resources Information Center

Sprague, Sheila; Madden, Kim; Dosanjh, Sonia; Petrisor, Brad; Schemitsch, Emil H.; Bhandari, Mohit

2012-01-01

Accurately identifying victims of intimate partner violence (IPV) can be a challenge for clinicians and clinical researchers. Multiple instruments have been developed and validated to identify IPV in patients presenting to health care practitioners, including the Woman Abuse Screening Tool (WAST) and the Partner Violence Screen (PVS). The purpose…

City and County Solar PV Training Program, Module 2: Screening and Identifying PV Projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elgqvist, Emma M

When screening and identifying PV projects, cities and counties should understand the different factors that impact the technical and economic potential of a PV project, the steps of the PV screening process, and how to use REopt Lite to screen a site for PV and storage project potential.

Breast cancer risk from different mammography screening practices.

PubMed

Bijwaard, Harmen; Brenner, Alina; Dekkers, Fieke; van Dillen, Teun; Land, Charles E; Boice, John D

2010-09-01

Mammography screening is an accepted procedure for early detection of breast tumors among asymptomatic women. Since this procedure involves the use of X rays, it is itself potentially carcinogenic. Although there is general consensus about the benefit of screening for older women, screening practices differ between countries. In this paper radiation risks for these different practices are estimated using a new approach. We model breast cancer induction by ionizing radiation in a cohort of patients exposed to frequent X-ray examinations. The biologically based, mechanistic model provides a better foundation for the extrapolation of risks to different mammography screening practices than empirical models do. The model predicts that the excess relative risk (ERR) doubles when screening starts at age 40 instead of 50 and that a continuation of screening at ages 75 and higher carries little extra risk. The number of induced fatal breast cancers is estimated to be considerably lower than derived from epidemiological studies and from internationally accepted radiation protection risks. The present findings, if used in a risk-benefit analysis for mammography screening, would be more favorable to screening than estimates currently recommended for radiation protection. This has implications for the screening ages that are currently being reconsidered in several countries.

Screening Intervals for Diabetic Retinopathy and Implications for Care.

PubMed

Scanlon, Peter H

2017-09-05

The purpose of this study is to review the evidence that lower risk groups who could safely be screened less frequently for sight-threatening diabetic retinopathy (DR) than annually. Data have demonstrated that people with no DR in either eye are at a low risk of progression to sight-threatening DR over a 2-year period (event rate 4.8 per 1000 person years), irrespective of whether the screening method is one-field non-mydriatic or two-field mydriatic digital photography. Low risk has been defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with risk factor data. The risk of an extension to 2 years is less than 5 per 1000 person years in a population with a national screening programme, and the general standard of diabetes care is relatively good, whether low risk is defined as no retinopathy on two consecutive screening episodes or no retinopathy on one screening episode combined with other risk factor data. The definition used in different populations is likely to depend on the availability of data.

Depression screening for patients with epilepsy in a primary care setting using the Patient Health Questionnaire-2 and the Neurological Disorders Depression Inventory for Epilepsy.

PubMed

Margrove, Kerrie; Mensah, Seth; Thapar, Ajay; Kerr, Michael

2011-08-01

Depression among people with a diagnosis of epilepsy is under-recognized. General practitioner (GP) screening for depression using a new scale developed specifically for patients with epilepsy, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), has not before been reported. The aims were to examine the process of GP screening for depression in patients with epilepsy employing the widely used Patient Health Questionnaire-2 (PHQ-2) and the NDDI-E; to determine the impact of screening on GP-recognized depression; and to ascertain depression predictors. Patients were screened via their GPs. A subset of participants underwent clinical interview to assess screener accuracy. Use of either instrument almost doubled the proportion of GP-recognized depression. Ninety-four percent of those interviewed found screening acceptable. More recent and frequent seizures predicted screening positive. The results suggest that screening for depression in patients with epilepsy via GPs improves detection of depression and is acceptable to interviewed patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Breast cancer screening practices of African migrant women in Australia: a descriptive cross-sectional study.

PubMed

Ogunsiji, Olayide Oluyemisi; Kwok, Cannas; Fan, Lee Chun

2017-04-17

Breast cancer is the most diagnosed cancer among women and a leading cause of mortality and morbidity, globally. Breast cancer mortality can be improved through routine cancer screening, yet migrant populations have lower participation rates. While African migrants are among the fastest growing migrant population in Australia, their breast cancer screening behaviour is under-studied. The aims of this study were to report breast cancer screening status of African migrant women and factors associated with their breast cancer screening behaviour in Australia. A descriptive, cross-sectional approach was utilised for this study. Two hundred and sixty four African migrant women aged 18-69 years and recruited from a number of organisations responded to a self-reported African version of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ). Main research variables are breast cancer screening practices and demographic characteristics and total scores on each of the BCSBQ subscales. Multivariable logistic regression analyses were performed to investigate the impact of the demographic variables on the likelihood of women in the target age range 50-74 years having screening practices as recommended. While most of the participants heard of breast awareness (76.1%) and mammogram (85.2%), only 11.4% practised monthly breast awareness, whereas 65.9% had ever had a mammogram as frequently as recommended. Age and employment were determining factors for participating in mammogram. Significant different scores were found in the "Practical barriers" between women at the target age who had and had not performed breast awareness (80.4 versus 77.5, p-value = 0.002) and mammogram (77.1 versus 70.3, p-value = 0.009) regularly as recommended. Moreover, attitudes towards general health check-ups subscale scores were significantly higher in women who had performed clinical breast examination as frequently as recommended than those who had not. The research reveals that practical barriers and attitudes towards general health check-ups are important factors to take into account in determining African migrant women's participation in breast cancer screening. Progress in reducing breast cancer deaths through early detection needs to focus on attitudinal change among African migrants.

Screening for Victims of Sex Trafficking in the Emergency Department: A Pilot Program

PubMed Central

Mumma, Bryn E.; Scofield, Marisa E.; Mendoza, Lydia P.; Toofan, Yalda; Youngyunpipatkul, Justin; Hernandez, Bryan

2017-01-01

Introduction Estimates suggest that hundreds of thousands of sex trafficking victims live in the United States. Several screening tools for healthcare professionals to identify sex trafficking victims have been proposed, but the effectiveness of these tools in the emergency department (ED) remains unclear. Our primary objective in this study was to evaluate the feasibility of a screening survey to identify adult victims of sex trafficking in the ED. We also compared the sensitivity of emergency physician concern and a screening survey for identifying sex trafficking victims in the ED and determined the most effective question(s) for identifying adult victims of sex trafficking. Methods We enrolled a convenience sample of medically stable female ED patients, age 18–40 years. Patients completed a 14-question survey. Physician concern for sex trafficking was documented prior to informing the physician of the survey results. A “yes” answer to any question or physician concern was considered a positive screen, and the patient was offered social work consultation. We defined a “true positive” as a patient admission for or social work documentation of sex trafficking. Demographic and clinical information were collected from the electronic medical record. Results We enrolled 143 patients, and of those 39 (27%, 95% confidence interval [CI] [20%–35%]) screened positive, including 10 (25%, 95% CI [13%–41%]) ultimately identified as victims of sex trafficking. Sensitivity of the screening survey (100%, 95% CI [74%–100%]) was better than physician concern (40%, 95% CI [12%–74%]) for identifying victims of sex trafficking, difference 60%, 95% CI [30%–90%]. Physician specificity (91%, 95% CI [85%–95%]), however, was slightly better than the screening survey (78%, 95% CI [70%–85%]), difference 13%, 95% CI [4%–21%]. All 10 (100%, 95%CI [74%–100%]) “true positive” cases answered “yes” to the screening question regarding abuse. Conclusion Identifying adult victims of sex trafficking in the ED is feasible. A screening survey appears to have greater sensitivity than physician concern, and a single screening question may be sufficient to identify all adult victims of sex trafficking in the ED. PMID:28611881

Screening for Victims of Sex Trafficking in the Emergency Department: A Pilot Program.

PubMed

Mumma, Bryn E; Scofield, Marisa E; Mendoza, Lydia P; Toofan, Yalda; Youngyunpipatkul, Justin; Hernandez, Bryan

2017-06-01

Estimates suggest that hundreds of thousands of sex trafficking victims live in the United States. Several screening tools for healthcare professionals to identify sex trafficking victims have been proposed, but the effectiveness of these tools in the emergency department (ED) remains unclear. Our primary objective in this study was to evaluate the feasibility of a screening survey to identify adult victims of sex trafficking in the ED. We also compared the sensitivity of emergency physician concern and a screening survey for identifying sex trafficking victims in the ED and determined the most effective question(s) for identifying adult victims of sex trafficking. We enrolled a convenience sample of medically stable female ED patients, age 18-40 years. Patients completed a 14-question survey. Physician concern for sex trafficking was documented prior to informing the physician of the survey results. A "yes" answer to any question or physician concern was considered a positive screen, and the patient was offered social work consultation. We defined a "true positive" as a patient admission for or social work documentation of sex trafficking. Demographic and clinical information were collected from the electronic medical record. We enrolled 143 patients, and of those 39 (27%, 95% confidence interval [CI] [20%-35%]) screened positive, including 10 (25%, 95% CI [13%-41%]) ultimately identified as victims of sex trafficking. Sensitivity of the screening survey (100%, 95% CI [74%-100%]) was better than physician concern (40%, 95% CI [12%-74%]) for identifying victims of sex trafficking, difference 60%, 95% CI [30%-90%]. Physician specificity (91%, 95% CI [85%-95%]), however, was slightly better than the screening survey (78%, 95% CI [70%-85%]), difference 13%, 95% CI [4%-21%]. All 10 (100%, 95%CI [74%-100%]) "true positive" cases answered "yes" to the screening question regarding abuse. Identifying adult victims of sex trafficking in the ED is feasible. A screening survey appears to have greater sensitivity than physician concern, and a single screening question may be sufficient to identify all adult victims of sex trafficking in the ED.

Supply-and-demand discrepancy in academic pigmented lesion clinics: a case for a new health care delivery model.

PubMed

Vickery, Erin L; Seidler, Elizabeth M; Jones, Todd E; Veledar, Emir; Chen, Suephy C

2014-11-01

There is an increasing demand for a limited number of pigmented lesion clinic (PLC) visits at dermatology centers. To determine the proportion of visits to PLCs that are more frequent ("additional screening") than the recommended ("standard") follow-up schedule and to determine if certain patient characteristics correlate with the demand for these visits. A retrospective medical chart review of all PLC visits at an academic dermatology center from October 2010 to January 2012. A total of 609 patients associated with 1756 visits were identified. Of these, 25 patients associated with 26 visits were excluded owing to lack of melanoma diagnosis or risk factors, leaving 584 patients and 1730 visits. Diagnoses of these patients included in situ and invasive melanoma, dysplastic nevi, Spitz nevi, atypical nevus syndrome, family history of melanoma only, and other risk factors. The mean (SD) age was 48 (16) years, and 235 (40.2%) of the patients were male. The proportion of additional screening visits compared with standard visits. Standard visits were defined as occurring at the following frequencies: annually for mildly dysplastic nevi, Spitz nevi, or solely family history of melanoma; biannually for the first year, then annually thereafter for moderately dysplastic nevi or atypical nevus syndrome; biannually for up to 3 years, then annually thereafter for severely dysplastic nevi or melanomas in situ; every 3 months for 2 years, biannually for the following 2 years, then annually thereafter for invasive melanoma. A total of 1400 visits (80.9%) were standard, 257 (14.9%) were for additional screening, and 73 (4.2%) were "problem focused." Thirty percent of patients had at least 1 additional screening visit. The distribution of diagnoses among standard vs additional screening visits differed significantly, with "family history only" and "other risk factors" taking up a larger percentage of standard visits (15.1%) than the percentage of additional screening visits (8.9%), and all other diagnoses being better represented among additional screening visits (P = .04). No particular patient characteristic described those who sought additional screening visits. A substantial proportion of additional screening PLC visits exist and are desired by all patients with pigmented lesions. We propose alternative clinic models, such as diagnosis-specific, adjunctive fee-for-additional-service, and teledermatology clinics to meet patient needs while creating resources to expand PLC visits.

Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

PubMed

Haedens, Vicki; Malagnac, Fabienne; Silar, Philippe

2005-06-01

Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

Is it useful to add acetaminophen to high-potency opioids in cancer-related pain?

PubMed

Corsi, Oscar; Pérez-Cruz, Pedro E

2017-05-04

Pain is one of the most frequent and relevant symptoms in cancer patients. The World Health Organization's analgesic ladder proposes the use of strong opioids associated with adjuvants such as acetaminophen or nonsteroidal anti-inflammatory drugs in step III. However, it is unclear whether adding acetaminophen to an analgesic regimen based on strong opioids has any benefit in cancer patients with moderate to severe pain. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified two systematic reviews including five randomized trials overall. We extracted data and generated a summary of findings table using the GRADE approach. We concluded that adding acetaminophen to strong opioids might make little or no difference in improving pain management in cancer patients.

Containerless preparation of advanced optical glasses: Experiment 77F095

NASA Technical Reports Server (NTRS)

Happe, R. A.; Kim, K. S.

1982-01-01

Containerless processing of optical glasses was studied in preparation for space shuttle MEA flight experiments. Ground based investigation, experiment/hardware coordination activities and development of flight experiment and sample characterization plans were investigated. In the ground based investigation over 100 candidate glass materials for space processing were screened and promising compositions were identified. The system of Nb2O5-TiO2-CaO was found to be very rich with containerless glass compositions and as extensive number of the oxides combinations were tried resulting in a glass formation ternary phase diagram. The frequent occurrence of glass formation by containerless processing among the compositions for which no glass formations were previously reported indicated the possibility and an advantage of containerless processing in a terrestrial environment.

Application of ToxCast High-Throughput Screening and ...

EPA Pesticide Factsheets

Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenesis Distruptors Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenssis Distruptors

Newborn Screening (NBS): Answers to Frequently Asked Questions

MedlinePlus

... states consider the NBS recommendations made by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children, a federal panel that reports to the Secretary of Health and Human Services. Some states may ...

Barriers to Breast and Cervical Cancer Screening in Singapore: a Mixed Methods Analysis.

PubMed

Malhotra, Chetna; Bilger, Marcel; Liu, Joy; Finkelstein, Eric

2016-01-01

In order to increase breast and cervical cancer screening uptake in Singapore, women's perceived barriers to screening need to be identified and overcome. Using data from both focus groups and surveys, we aimed to assess perceived barriers and motivations for breast and cervical cancer screening. We conducted 8 focus groups with 64 women, using thematic analysis to identify overarching themes related to women's attitudes towards screening. Based on recurring themes from focus groups, several hypotheses regarding potential barriers and motivations to screen were generated and tested through a national survey of 801 women aged 25-64. Focus group participants had misconceptions related to screening, believing that the procedures were painful. Cost was an issue, as well as efficacy and fatalism. By identifying barriers to and motivators for screening through a mixed-method design that has both nuance and external validity, this study offers valuable suggestions to policymakers to improve breast and cervical cancer screening uptake in Singapore.

Predicting plant attractiveness to pollinators with passive crowdsourcing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bahlai, Christie A.; Landis, Douglas A.

Global concern regarding pollinator decline has intensified interest in enhancing pollinator resources in managed landscapes. These efforts frequently emphasize restoration or planting of flowering plants to provide pollen and nectar resources that are highly attractive to the desired pollinators. However, determining exactly which plant species should be used to enhance a landscape is difficult. Empirical screening of plants for such purposes is logistically daunting, but could be streamlined by crowdsourcing data to create lists of plants most probable to attract the desired pollinator taxa. People frequently photograph plants in bloom and the Internet has become a vast repository of suchmore » images. A proportion of these images also capture floral visitation by arthropods. Here, we test the hypothesis that the abundance of floral images containing identifiable pollinator and other beneficial insects is positively associated with the observed attractiveness of the same species in controlled field trials from previously published studies. We used Google Image searches to determine the correlation of pollinator visitation captured by photographs on the Internet relative to the attractiveness of the same species in common-garden field trials for 43 plant species. From the first 30 photographs, which successfully identified the plant, we recorded the number of Apis (managed honeybees), non-Apis (exclusively wild bees) and the number of bee-mimicking syrphid flies. We used these observations from search hits as well as bloom period (BP) as predictor variables in Generalized Linear Models (GLMs) for field-observed abundances of each of these groups. We found that non-Apis bees observed in controlled field trials were positively associated with observations of these taxa in Google Image searches (pseudo-R 2 of 0.668). Syrphid fly observations in the field were also associated with the frequency they were observed in images, but this relationship was weak. Apis bee observations were not associated with Internet images, but were slightly associated with BP. Our results suggest that passively crowdsourced image data can potentially be a useful screening tool to identify candidate plants for pollinator habitat restoration efforts directed at wild bee conservation. Increasing our understanding of the attractiveness of a greater diversity of plants increases the potential for more rapid and efficient research in creating pollinator-supportive landscapes.« less

Predicting plant attractiveness to pollinators with passive crowdsourcing

DOE PAGES

Bahlai, Christie A.; Landis, Douglas A.

2016-06-01

Global concern regarding pollinator decline has intensified interest in enhancing pollinator resources in managed landscapes. These efforts frequently emphasize restoration or planting of flowering plants to provide pollen and nectar resources that are highly attractive to the desired pollinators. However, determining exactly which plant species should be used to enhance a landscape is difficult. Empirical screening of plants for such purposes is logistically daunting, but could be streamlined by crowdsourcing data to create lists of plants most probable to attract the desired pollinator taxa. People frequently photograph plants in bloom and the Internet has become a vast repository of suchmore » images. A proportion of these images also capture floral visitation by arthropods. Here, we test the hypothesis that the abundance of floral images containing identifiable pollinator and other beneficial insects is positively associated with the observed attractiveness of the same species in controlled field trials from previously published studies. We used Google Image searches to determine the correlation of pollinator visitation captured by photographs on the Internet relative to the attractiveness of the same species in common-garden field trials for 43 plant species. From the first 30 photographs, which successfully identified the plant, we recorded the number of Apis (managed honeybees), non-Apis (exclusively wild bees) and the number of bee-mimicking syrphid flies. We used these observations from search hits as well as bloom period (BP) as predictor variables in Generalized Linear Models (GLMs) for field-observed abundances of each of these groups. We found that non-Apis bees observed in controlled field trials were positively associated with observations of these taxa in Google Image searches (pseudo-R 2 of 0.668). Syrphid fly observations in the field were also associated with the frequency they were observed in images, but this relationship was weak. Apis bee observations were not associated with Internet images, but were slightly associated with BP. Our results suggest that passively crowdsourced image data can potentially be a useful screening tool to identify candidate plants for pollinator habitat restoration efforts directed at wild bee conservation. Increasing our understanding of the attractiveness of a greater diversity of plants increases the potential for more rapid and efficient research in creating pollinator-supportive landscapes.« less

Predicting plant attractiveness to pollinators with passive crowdsourcing

PubMed Central

Bahlai, Christie A.; Landis, Douglas A.

2016-01-01

Global concern regarding pollinator decline has intensified interest in enhancing pollinator resources in managed landscapes. These efforts frequently emphasize restoration or planting of flowering plants to provide pollen and nectar resources that are highly attractive to the desired pollinators. However, determining exactly which plant species should be used to enhance a landscape is difficult. Empirical screening of plants for such purposes is logistically daunting, but could be streamlined by crowdsourcing data to create lists of plants most probable to attract the desired pollinator taxa. People frequently photograph plants in bloom and the Internet has become a vast repository of such images. A proportion of these images also capture floral visitation by arthropods. Here, we test the hypothesis that the abundance of floral images containing identifiable pollinator and other beneficial insects is positively associated with the observed attractiveness of the same species in controlled field trials from previously published studies. We used Google Image searches to determine the correlation of pollinator visitation captured by photographs on the Internet relative to the attractiveness of the same species in common-garden field trials for 43 plant species. From the first 30 photographs, which successfully identified the plant, we recorded the number of Apis (managed honeybees), non-Apis (exclusively wild bees) and the number of bee-mimicking syrphid flies. We used these observations from search hits as well as bloom period (BP) as predictor variables in Generalized Linear Models (GLMs) for field-observed abundances of each of these groups. We found that non-Apis bees observed in controlled field trials were positively associated with observations of these taxa in Google Image searches (pseudo-R2 of 0.668). Syrphid fly observations in the field were also associated with the frequency they were observed in images, but this relationship was weak. Apis bee observations were not associated with Internet images, but were slightly associated with BP. Our results suggest that passively crowdsourced image data can potentially be a useful screening tool to identify candidate plants for pollinator habitat restoration efforts directed at wild bee conservation. Increasing our understanding of the attractiveness of a greater diversity of plants increases the potential for more rapid and efficient research in creating pollinator-supportive landscapes. PMID:27429762

Breast cancer and screening in persons with an intellectual disability living in institutions in France.

PubMed

Trétarre, B; Bourgarel, S; Stoebner-Delbarre, A; Jacot, W; Bessaoud, F; Satge, D

2017-03-01

We aimed to describe, among a population of women with intellectual disabilities (ID) living in institutions in France, the characteristics in whom breast cancer (BC) was diagnosed and of those who participated in BC screening. Study was performed in 2009 among a random, representative sample of women with ID living in institutions in France. Participants answered a questionnaire either directly by themselves, or with the help of an intermediary. In total, 978 women with ID aged over 18 years were included, and 14 were diagnosed with BC. The incidence observed in this sample of women with ID is similar to that of the general population (standardised incidence ratio, SIR 0.857, 95% confidence interval (CI) 0.42-1.53). Average age at diagnosis was 47.8 years, and the risk of developing BC before the age of 50 was 2.03% (0.4-3.66). This risk was not significantly different from that of the general population (2.4%, 1.0-3.78). Obesity was almost twice as frequent in women who had BC as compared to those without BC (43% vs. 22.5%, P = 0.0196). Among the 310 women aged >50 years and eligible for the national BC screening programme, 238 (77%) had already had at least one mammogram, and 199 had had it within the previous 2 years. Adherence to the screening programme was 64.2% (199/310) in the participating institutions. This rate was slightly higher than the national average of 62% for the same period. The results of this study show that BC is equally as frequent among women with ID living in institutions as in the general population, and occurs at around the same age. Obesity was significantly more frequent among women in whom BC was diagnosed in our study. Participation in BC screening is slightly higher among women with ID living in institutions than among the general population. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Identifying Relationships between High-Risk Sexual Behaviors and Screening Positive for Chlamydia and Gonorrhea in School-Wide Screening Events

ERIC Educational Resources Information Center

Salerno, Jennifer; Darling-Fisher, Cindy; Hawkins, Nicole M.; Fraker, Elizabeth

2013-01-01

Background: This article describes a school-wide sexually transmitted infection (STI) screening to identify adolescent high-risk sexual behaviors, STI history/incidence, and presence of chlamydia and gonorrhea, and examines relationships between high-risk behaviors and screening positive for chlamydia and gonorrhea in an alternative high school…

Regional Differences as Barriers to Body Mass Index Screening Described by Ohio School Nurses

ERIC Educational Resources Information Center

Stalter, Ann M.; Chaudry, Rosemary V.; Polivka, Barbara J.

2011-01-01

Background: Body mass index (BMI) screening is advocated by the National Association of School Nurses (NASN). Research identifying barriers to BMI screening in public elementary school settings has been sparse. The purpose of the study was to identify barriers and facilitating factors of BMI screening practices among Ohio school nurses working in…

[Malnutrition screening in hospitalized children: influence of the hospital unit on its management].

PubMed

Marteletti, O; Caldari, D; Guimber, D; Mention, K; Michaud, L; Gottrand, F

2005-08-01

The aims of this study were to assess the prevalence of malnutrition in a pediatric population hospitalized in a French regional hospital and to evaluate the influence of type of hospital unit (pediatric or not) in the screening and the management of malnutrition. This one-day cross-sectional survey was performed in three different seasons during 2003. Every child aged 2 months to 16 years old, hospitalized for more than 48 hours was included. Weight for height, Z-score and Body Mass Index Z-score were used for nutritional assessment. Type of hospitalisation unit, date of admission, associated diagnosis, screening and treatment of malnutrition were also taken into account. Two hundred and eighty hospitalized children were undernourished (11%) and thirty-one children were obese (11%) with no difference in prevalence of malnutrition between pediatric and non-pediatric units. At the time of the study, malnutrition was recognized in one third of the children, at a similar rate whatever the type of hospitalized unit. The children hospitalized in pediatrics wards benefited more frequently from nutritional intervention, i.e. dietician care (43 vs. 16% P < 0.01). Prevalence of malnutrition in hospitalized children is low and the same in pediatric or non-pediatric units. Screening of malnutrition remains unsatisfactory in hospital. However, malnutrition is more frequently treated in pediatric unit compared with non-pediatric unit.

[Neurophysiological basis and clinical tests for assessment of X-linked color vision deficiencies in school children].

PubMed

Rigaudière, F; Leid, J; Viénot, F; Le Gargasson, J-F

2006-01-01

Vision screening of school children at 5-6 years of age must include color vision screening. X-linked dyschromatopsia is the most frequent disorder affecting 8% of boys and 0.4% of girls. This paper presents the physiology of these deficiencies caused by an alteration of the spectral absorption properties of one of the cone pigments (protanomalous or deuteranomalous trichromats) or the absence of one of the pigments (protanopia or deuteranopia), the most frequent. Absence of two of the pigments (blue cone monochromacy) is very rare and differs from achromatopsia. The physiological basis of the main tests for easy clinical screening are presented. Testing methods designed for children are reviewed. The Ishihara test is the most widely used screening test specific for congenital color defects. If the plates are correctly read, the child has normal color vision. If not, arrangement tests such as Panel D 15 and desaturated Panel D 15 tests can be used to diagnose the type of the defect (protan or deutan) and grade the degree of color deficiency according to a strategy adapted to children. Examples of results are presented for each axis along which caps are confused, providing a quick and easy preliminary diagnosis. Early detection of color vision malfunction in children allows parents and teachers to make necessary adjustments to the teaching methods for appropriate learning.

Diagnostic methods of TSH in thyroid screening tests.

PubMed

Matyjaszek-Matuszek, Beata; Pyzik, Aleksandra; Nowakowski, Andrzej; Jarosz, Mirosław J

2013-01-01

Reliable and quick thyreologic diagnostics, as well as verification of the effectiveness of the therapy undertaken, is of great importance for the state of health of society. The measurement of plasma TSH is the commonly accepted and most sensitive screening test for primary thyroid disorders, which are the most frequent diseases related to the endocrine glands. At present, the available methods for the determination of TSH are characterized by high sensitivity ≤0.01 µIU/ml and lack of cross-reactivity. However, many drugs and substances, as well as pathological conditions, may affect the TSH level. evaluation of contemporary laboratory methods for the determination of TSH and the principles of interpretation of screening tests. In many countries, the TSH test is the only test performed in the diagnostics of thyroid function; nevertheless, it seems that for genuine and objective assessment of thyroid status the TSH level, together with FT4 level, should be absolutely determined, which allows the differentiation and assessment of the intensity of thyroid function disorders and foresee its consequences. The interpretation of TSH results in screening tests is different in such population groups as: children aged under 14, pregnant women, the elderly, and patients with non-thyroidal illnesses. From among currently used laboratory methods for determination of TSH levels, third generation non-isotopic methods are most frequently recommended, especially the method of immunochemiluminescence.

Screening and characterization of Staphylococcus aureus from ophthalmology clinic surfaces: a proposed surveillance tool

PubMed Central

Reem, Rachel E.; Van Balen, Joany; Hoet, Armando E.; Cebulla, Colleen M.

2014-01-01

Purpose To screen environmental surfaces of an outpatient ophthalmic clinic for methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA); to identify the most commonly contaminated surfaces; and to phenotype and genotype all collected isolates Design A single institution, one-year prospective environmental study Methods Commonly touched surfaces from examination rooms and common areas were targeted and sampled on a quarterly basis for one year. Samples were collected using electrostatic cloths and swabs. S. aureus was isolated using non-selective and selective media. Morphological characteristics and standard biological testing were used to confirm staphylococcal species. S. aureus isolates were phenotypically (Kirby-Bauer method) and genotypically characterized (mecA confirmation, SCCmec typing and pulsed-field gel electrophoresis). Dendrogram analysis was used to establish genetic relatedness between the isolates. Results Of 112 total samples, 27 (24%) and 5 (4%) were MSSA- and MRSA-positive, respectively. Both community-associated (SCCmec IV, USA300) and hospital-associated (SCCmec II, USA100) MRSA isolates were found. No single surface remained consistently positive with the same isolate over time and molecular analysis demonstrated high levels of diversity among isolates. Doorknobs, slit-lamp head/chinrests, and computer keyboards were frequently contaminated. Conclusions The proposed surveillance protocol successfully allowed the detection of both MSSA and MRSA contaminating important high-touch surfaces in a representative ophthalmology clinic. Frequently contaminated surfaces must be targeted for routine cleaning and disinfection as a there is a constant introduction of clones over time. Hence, other clinics may consider implementing and adapting surveillance tools, as the one here described, to help them control these important nosocomial pathogens. PMID:24412125

Pain in Underserved Community-Dwelling Chinese American Cancer Patients: Demographic and Medical Correlates

PubMed Central

Lam, Kin; Homel, Peter; Chen, Jack; Chang, Victor T.; Zhou, Juanyi; Chan, Selina; Lam, Wan Ling; Portenoy, Russell

2011-01-01

Background. Little is known about cancer pain in Chinese Americans. The objective of this study was to describe the epidemiology of pain in this population. This information is needed to identify and address unmet clinical needs for culturally relevant interventions targeting pain and its consequences. Methods. A consecutive sample of underserved ethnic Chinese patients in a large community-based oncology practice was screened for persistent or frequent pain. Those patients with pain completed translated instruments assessing demographics, linguistic acculturation, disease-related characteristics, and pain-related characteristics. Results. Of 312 patients screened, 178 (57.1%) reported frequent or persistent pain, 175 were eligible, and 170 participated. Most participants (85.9%) were born in China and 84.7% overall spoke Cantonese only. The most common cancers were gastrointestinal (28.2%), lung (21.8%), breast (20.6%), head and neck (12.9%), and genitourinary (4.7%); 43.5% had metastatic disease. The mean worst pain severity on a 0–10 numeric scale was 4.7 (standard deviation, 2.4), with 28.2% of patients rating their worst pain at ≥7 of 10. Although 37.6% used opioids and 47.1% used nonopioids, 45.8% reported “little” or “no” pain relief from medications. Complementary or alternative medicine therapies for cancer pain were used by 35.8%. In multiple regression analyses, worst pain was positively associated with acculturation to the English language and opioid therapy, and pain-related distress was positively associated with opioid therapy. Conclusion. Pain is prevalent among community-dwelling, ethnic Chinese American cancer patients. Additional studies are needed to confirm these results and investigate the finding that higher linguistic acculturation is associated with reports of more intense pain. PMID:21402591

Smartphone, tablet computer and e-reader use by people with vision impairment.

PubMed

Crossland, Michael D; Silva, Rui S; Macedo, Antonio F

2014-09-01

Consumer electronic devices such as smartphones, tablet computers, and e-book readers have become far more widely used in recent years. Many of these devices contain accessibility features such as large print and speech. Anecdotal experience suggests people with vision impairment frequently make use of these systems. Here we survey people with self-identified vision impairment to determine their use of this equipment. An internet-based survey was advertised to people with vision impairment by word of mouth, social media, and online. Respondents were asked demographic information, what devices they owned, what they used these devices for, and what accessibility features they used. One hundred and thirty-two complete responses were received. Twenty-six percent of the sample reported that they had no vision and the remainder reported they had low vision. One hundred and seven people (81%) reported using a smartphone. Those with no vision were as likely to use a smartphone or tablet as those with low vision. Speech was found useful by 59% of smartphone users. Fifty-one percent of smartphone owners used the camera and screen as a magnifier. Forty-eight percent of the sample used a tablet computer, and 17% used an e-book reader. The most frequently cited reason for not using these devices included cost and lack of interest. Smartphones, tablet computers, and e-book readers can be used by people with vision impairment. Speech is used by people with low vision as well as those with no vision. Many of our (self-selected) group used their smartphone camera and screen as a magnifier, and others used the camera flash as a spotlight. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia

PubMed Central

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-01-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)-gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid-repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF-gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA-box binding protein associated factor 1 and CCCTC-binding factor, which may be potential therapeutic targets of AML. PMID:28498449

Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia.

PubMed

Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

2017-07-01

Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)‑gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein‑DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid‑repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF‑pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF‑gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA‑box binding protein associated factor 1 and CCCTC‑binding factor, which may be potential therapeutic targets of AML.

Correlates of frequent gambling and gambling-related chasing behaviors in individuals with schizophrenia-spectrum disorders.

PubMed

Yakovenko, Igor; Fortgang, Rebecca; Prentice, Jennifer; Hoff, Rani A; Potenza, Marc N

2018-05-23

Background and aims Published research on the relationship between disordered gambling and schizophrenia is limited. However, existing data suggest that individuals with schizophrenia/schizoaffective disorder may have a high prevalence of co-occurring disordered gambling. As such, effective strategies for screening and assessing gambling-related problems in individuals with psychosis are needed. The goal of this study was to explore the correlates of increased gambling frequency and chasing behavior, a hallmark feature of gambling disorder, in a sample of individuals with schizophrenia and schizoaffective disorders. Methods Data from 336 participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder were used to examine differences between non-gamblers, infrequent gamblers, frequent gamblers who do not report chasing, and frequent gamblers who report chasing on a variety of associated features and symptoms of schizophrenia and disordered gambling. Results and discussion The results of the study support the conclusion that chasing behavior in individuals with schizophrenia/schizoaffective disorder lies on a continuum of severity, with more frequent gamblers endorsing greater chasing. Chasing was also associated with indicators of lower functioning across co-occurring disorders, such as greater problems with alcohol and drugs, greater gambling involvement, and a family history of gambling problems. The findings from the study suggest the utility of screening for chasing behavior as a brief and efficient strategy for assessing risk of gambling problems in individuals with psychotic-spectrum disorders.

Risk stratification in cervical cancer screening by complete screening history: Applying bioinformatics to a general screening population.

PubMed

Baltzer, Nicholas; Sundström, Karin; Nygård, Jan F; Dillner, Joakim; Komorowski, Jan

2017-07-01

Women screened for cervical cancer in Sweden are currently treated under a one-size-fits-all programme, which has been successful in reducing the incidence of cervical cancer but does not use all of the participants' available medical information. This study aimed to use women's complete cervical screening histories to identify diagnostic patterns that may indicate an increased risk of developing cervical cancer. A nationwide case-control study was performed where cervical cancer screening data from 125,476 women with a maximum follow-up of 10 years were evaluated for patterns of SNOMED diagnoses. The cancer development risk was estimated for a number of different screening history patterns and expressed as Odds Ratios (OR), with a history of 4 benign cervical tests as reference, using logistic regression. The overall performance of the model was moderate (64% accuracy, 71% area under curve) with 61-62% of the study population showing no specific patterns associated with risk. However, predictions for high-risk groups as defined by screening history patterns were highly discriminatory with ORs ranging from 8 to 36. The model for computing risk performed consistently across different screening history lengths, and several patterns predicted cancer outcomes. The results show the presence of risk-increasing and risk-decreasing factors in the screening history. Thus it is feasible to identify subgroups based on their complete screening histories. Several high-risk subgroups identified might benefit from an increased screening density. Some low-risk subgroups identified could likely have a moderately reduced screening density without additional risk. © 2017 UICC.

Screening for Behavioral Health Issues in Children Enrolled in Massachusetts Medicaid

PubMed Central

Penfold, Robert; Arsenault, Lisa; Zhang, Fang; Murphy, Michael; Wissow, Larry

2014-01-01

OBJECTIVES: To understand mandated behavioral health (BH) screening in Massachusetts Medicaid including characteristics of screened children, predictors of positive screens, and whether screening identifies children without a previous BH history. METHODS: Massachusetts mandated BH screening in particularly among underidentified groups. 2008. Providers used a billing code and modifier to indicate a completed screen and whether a BH need was identified. Using MassHealth claims data, children with ≥300 days of eligibility in fiscal year (FY) 2009 were identified and categorized into groups based on first use of the modifier, screening code, or claim. Bivariate analyses were conducted to determine differences among groups. BH history was examined by limiting the sample to those continuously enrolled in FY 2008 and 2009. Multivariate logistic regression was used to determine predictors of positive screens. RESULTS: Of 355 490 eligible children, 46% had evidence of screening. Of those with modifiers, 12% were positive. Among continuously enrolled children (FY 2008 and FY 2009) with evidence of screening, 43% with positive modifiers had no BH history. This “newly identified” group were more likely to be female, younger, minority, and from rural residences (P < .0001). Among children with modifiers; gender (male), age (5–7), being in foster care, recent BH history, and Hispanic ethnicity predicted having a positive modifier. CONCLUSIONS: The high rate of newly identified Medicaid children with a BH need suggests that screening is performing well, particularly among underidentified groups. To better assess screening value, future work on cost-effectiveness and the impact on subsequent mental health treatment is needed. PMID:24298005

An Overview of Inflammatory Bowel Disease: General Consideration and Genetic Screening Approach in Diagnosis of Early Onset Subsets

PubMed Central

Nemati, Shahram; Teimourian, Shahram

2017-01-01

Inflammatory bowel disease (IBD) is the consequence of an aberrant hemostasis of the immune cells at the gut mucosal border. Based on clinical manifestation, laboratory tests, radiological studies, endoscopic and histological features, this disease is divided into three main types including Crohn’s disease (CD), Ulcerative colitis (UC), and IBDunclassified (IBD-U). IBD is frequently presented in adults, but about 20% of IBD cases are diagnosed during childhood called pediatric IBD (PIBD). Some patients in the latter group emerge the first symptoms during infancy or under 5 years of age named infantile and very early onset IBD (VEO-IBD), respectively. These subtypes make a small fraction of PIBD, but they have exclusive phenotypic and genetic characteristics such that they are accompanied by severe disease course and resistance to conventional therapy. In this context, understanding the underlying molecular pathology opens a promising field for individualized and effective treatment. Here, we describe current hypotheses on IBD pathophysiology then explain the new idea about genetic screening technology as a good potential approach to identify the causal variants early in the disease manifestation, which is especially important for the fast and accurate treatment of VEO-IBD. PMID:28638582

Diverse Antibiotic Resistance Genes in Dairy Cow Manure

PubMed Central

Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

2014-01-01

ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

Methylation of TFPI2 in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer

PubMed Central

Glöckner, Sabine C.; Dhir, Mashaal; Yi, Joo Mi; McGarvey, Kelly E.; Van Neste, Leander; Louwagie, Joost; Chan, Timothy A.; Kleeberger, Wolfram; de Bruïne, Adriaan P.; Smits, Kim M.; Khalid-de Bakker, Carolina A.J.; Jonkers, Daisy M.A.E.; Stockbrügger, Reinhold W.; Meijer, Gerrit A.; Oort, Frank A.; Iacobuzio-Donahue, Christine; Bierau, Katja; Herman, James G.; Baylin, Stephen B.; Van Engeland, Manon; Schuebel, Kornel E.; Ahuja, Nita

2011-01-01

We have used a gene expression array–based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)–marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA–based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future. PMID:19435926

Aberrantly methylated DNA as a biomarker in breast cancer.

PubMed

Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

2013-01-01

Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

Conservation of indigenous knowledge of medicinal plants of Western Himalayan region Rawalakot, Azad Kashmir, Pakistan.

PubMed

Hussain, Sajjad; Murtaza, Ghulam; Mehmood, Ansar; Qureshi, Rizwana Aleem

2017-05-01

The aim of present was to document indigenous knowledge of medicinal plants traditionally used by inhabitants of Rawalakot Azad Kashmir and to screen selected medicinal plants for their antibacterial potential. Several field surveys were conducted to document indigenous knowledge of medicinal plants through interviews from local inhabitants during 2010-2013. During the study, 58 plant species, belonging to 37 families, were identified and their medicinal uses were recorded. Ethnobotanical data indicates that inhabitants of Rawalakot use medicinal plant mainly for the treatment of stomach, liver and sexual disorders. Usually fresh plant materials were used for medicinal preparations and administrated orally. Among all the species studied, three most frequently used medicinal plants Achillea millefolium, Berberis lycium and Zanthoxylum armatum were screened for their antibacterial potential by using disc diffusion method. The crude aqueous, petroleum ether and ethanolic extracts were found to be very active against selected bacterial strains. The present study contributes significantly to the medicinal plant knowledge and shows that medicinal plant knowledge is deteriorating among younger generations. Therefore, further research is needed to document indigenous knowledge, to find conservation status of medicinal plant species and to find antimicrobial compounds for more sophisticated usage of medicinal plants in future.

Consistency and sources of divergence in recommendations on screening with questionnaires for presently experienced health problems or symptoms: a comparison of recommendations from the Canadian Task Force on Preventive Health Care, UK National Screening Committee, and US Preventive Services Task Force.

PubMed

Thombs, Brett D; Saadat, Nazanin; Riehm, Kira E; Karter, Justin Michael; Vaswani, Akansha; Andrews, Bonnie K; Simons, Peter; Cosgrove, Lisa

2017-08-09

Recently, health screening recommendations have gone beyond screening for early-stage, asymptomatic disease to include "screening" for presently experienced health problems and symptoms using self-report questionnaires. We examined recommendations from three major national guideline organizations to determine the consistency of recommendations, identify sources of divergent recommendations, and determine if guideline organizations have identified any direct randomized controlled trial (RCT) evidence for the effectiveness of questionnaire-based screening. We reviewed recommendation statements listed by the Canadian Task Force on Preventive Health Care (CTFPHC), the United Kingdom National Screening Committee (UKNSC), and the United States Preventive Services Task Force (USPSTF) as of 5 September 2016. Eligible recommendations focused on using self-report questionnaires to identify patients with presently experienced health problems or symptoms. Within each recommendation and accompanying evidence review we identified screening RCTs. We identified 22 separate recommendations on questionnaire-based screening, including three CTFPHC recommendations against screening, eight UKNSC recommendations against screening, four USPSTF recommendations in favor of screening (alcohol misuse, adolescent depression, adult depression, intimate partner violence), and seven USPSTF recommendations that did not recommend for or against screening. In the four cases where the USPSTF recommended screening, either the CTFPHC, the UKNSC, or both recommended against. When recommendations diverged, the USPSTF expressed confidence in benefits based on indirect evidence, evaluated potential harms as minimal, and did not consider cost or resource use. CTFPHC and UKNSC recommendations against screening, on the other hand, focused on the lack of direct evidence of benefit and raised concerns about harms to patients and resource use. Of six RCTs that directly evaluated screening interventions, five did not report any statistically significant primary or secondary health outcomes in favor of screening, and one trial reported equivocal results. Only the USPSTF has made any recommendations for screening with questionnaires for presently experienced problems or symptoms. The CTFPHC and UKNSC recommended against screening in all of their recommendations. Differences in recommendations appear to reflect differences in willingness to assume benefit from indirect evidence and different approaches to assessing possible harms and resource consumption. There were no examples in any recommendations of RCTs with direct evidence of improved health outcomes.

Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy.

PubMed

Egner, John M; Jensen, Davin R; Olp, Michael D; Kennedy, Nolan W; Volkman, Brian F; Peterson, Francis C; Smith, Brian C; Hill, R Blake

2018-03-02

An academic chemical screening approach was developed by using 2D protein-detected NMR, and a 352-chemical fragment library was screened against three different protein targets. The approach was optimized against two protein targets with known ligands: CXCL12 and BRD4. Principal component analysis reliably identified compounds that induced nonspecific NMR crosspeak broadening but did not unambiguously identify ligands with specific affinity (hits). For improved hit detection, a novel scoring metric-difference intensity analysis (DIA)-was devised that sums all positive and negative intensities from 2D difference spectra. Applying DIA quickly discriminated potential ligands from compounds inducing nonspecific NMR crosspeak broadening and other nonspecific effects. Subsequent NMR titrations validated chemotypes important for binding to CXCL12 and BRD4. A novel target, mitochondrial fission protein Fis1, was screened, and six hits were identified by using DIA. Screening these diverse protein targets identified quinones and catechols that induced nonspecific NMR crosspeak broadening, hampering NMR analyses, but are currently not computationally identified as pan-assay interference compounds. The results established a streamlined screening workflow that can easily be scaled and adapted as part of a larger screening pipeline to identify fragment hits and assess relative binding affinities in the range of 0.3-1.6 mm. DIA could prove useful in library screening and other applications in which NMR chemical shift perturbations are measured. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

How to report and interpret screening test properties: guidelines for driving researchers.

PubMed

Weaver, Bruce; Walter, Stephen D; Bédard, Michel

2014-01-01

One important goal of driving research is the development of a short but valid office-based screening test for fitness to drive of aging drivers. Several candidate tests have been proposed already, and no doubt others will be proposed in the future. It might seem obvious that authors advocating for the adoption of a particular screening test or procedure should report sensitivity, specificity, and other common screening test properties. Unfortunately, driving researchers have frequently failed to report any screening test properties. Others have reported screening test properties but have made basic mistakes such as calculating predictive values of positive and negative tests but reporting them incorrectly as sensitivity and specificity. These omissions and errors suggest that some driving researchers may be unaware of the importance of accurately reporting test properties when proposing a screening procedure and that others may need a refresher on how to calculate and interpret the most common screening test properties. Many good learning resources for screening and diagnostic tests are available, but most of them are intended for students and researchers in medicine, epidemiology, or public health. We hope that this tutorial in a prominent transportation journal will help lead to improved reporting and interpretation of screening test properties in articles that assess the usefulness of potential screening tools for fitness to drive.

Health-care providers' perceptions, attitudes towards and recommendation practice of cervical cancer screening.

PubMed

Hweissa, N Ab; Lim, J N W; Su, T T

2016-09-01

In Libya, cervical cancer is ranked third as the most frequent cancer among women with early diagnosis being shown to reduce morbidity and mortality. Health-care providers can influence women's screening behaviours, and their lack of recommendations for screening can be one of the barriers that affect women's participation in screening programmes. This study aims to assess the health-care provider's perception around cervical cancer screening. In-depth, face-to-face interviews were conducted with 16 health-care providers, from both public and private sectors in Az-Zawiya city, Libya, between February and July of 2014. The interviews were recorded and transcribed, then analysed using thematic analysis. Our findings suggest that health-care providers did not provide sufficient information regarding cervical cancer screening for women who attend health-care facilities. The results highlight the role played by health-care professionals in motivating women to attend cervical cancer screening programs, and the need for health education of health-care providers to offer a precious advice regarding the screening. On the other hand, health-care providers highlighted that implementation of reminding system of cervical cancer screening will support them to improve screening attendance. In addition, health-care providers stressed the necessity for educational and awareness campaigns of cervical cancer screening among Libyan women. © 2016 John Wiley & Sons Ltd.

A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat

PubMed Central

2010-01-01

Background Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes) encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (Triticum aestivum L.) is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation) that frequently generate whole-gene deletions. Results To facilitate the screening for specific homoeologous gene deletions in hexaploid wheat, we have developed a TaqMan qPCR-based method that allows high-throughput detection of deletions in homoeologous copies of any gene of interest, provided that sufficient polymorphism (as little as a single nucleotide difference) amongst homoeologues exists for specific probe design. We used this method to identify deletions of individual TaPFT1 homoeologues, a wheat orthologue of the disease susceptibility and flowering regulatory gene PFT1 in Arabidopsis. This method was applied to wheat nullisomic-tetrasomic lines as well as other chromosomal deletion lines to locate the TaPFT1 gene to the long arm of chromosome 5. By screening of individual DNA samples from 4500 M2 mutant wheat lines generated by heavy ion irradiation, we detected multiple mutants with deletions of each TaPFT1 homoeologue, and confirmed these deletions using a CAPS method. We have subsequently designed, optimized, and applied this method for the screening of homoeologous deletions of three additional wheat genes putatively involved in plant disease resistance. Conclusions We have developed a method for automated, high-throughput screening to identify deletions of individual homoeologues of a wheat gene. This method is also potentially applicable to other polyploidy plants. PMID:21114819

What factors influence health professionals to use decision aids for Down syndrome prenatal screening?

PubMed

Lépine, Johanie; Leiva Portocarrero, Maria Esther; Delanoë, Agathe; Robitaille, Hubert; Lévesque, Isabelle; Rousseau, François; Wilson, Brenda J; Giguère, Anik M C; Légaré, France

2016-09-05

Health professionals are expected to engage pregnant women in shared decision making to help them make informed values-based decisions about prenatal screening. Patient decision aids (PtDAs) foster shared decision-making, but are rarely used in this context. Our objective was to identify factors that could influence health professionals to use a PtDA for decisions about prenatal screening for Down syndrome during a clinical pregnancy follow-up. We planned to recruit a purposive sample of 45 health professionals (obstetrician-gynecologists, family physicians and midwives) involved in the care of pregnant women in three clinical sites (15 per site). Participating health professionals first watched a video showing two simulated consecutive prenatal follow-up consultations during which a pregnant woman, her partner and a health professional used a PtDA about Down syndrome prenatal screening. Participants were then interviewed about factors that would influence their use of the PtDA. Questions were based on the Theoretical Domains Framework. We performed content analyses of transcribed verbatim interviews. Out of 42 eligible health professionals approached, 36 agreed to be interviewed (86 % response rate). Of these, 27 were female (75 %), nine were obstetrician-gynecologists (25 %), 15 were family physicians (42 %), and 12 were midwives (33 %), with a mean age of 42.1 ± 11.6 years old. We identified 35 distinct factors reported by 20 % or more participants that were mapped onto 10 of the 12 of the Theoretical Domains Framework domains. The six most frequently mentioned factors influencing use of the PtDA were: 1) a positive appraisal (n = 29, 81 %, beliefs about consequences domain); 2) its availability in the office (n = 27, 75 %, environmental context and resources domain); 3) colleagues' approval (n = 27, 75 %, social influences domain); 4) time constraints (n = 26, 72 %, environmental context and resources domain); 5) finding it a relevant source of information (n = 24, 67 %, motivation and goals domain); and 6) not knowing any PtDAs (n = 23, 64 %, knowledge domain). Appraisal, PtDA availability, peer approval, time concerns, evidence and PtDA awareness all affect whether health professionals are likely to use a PtDA to help pregnant women make informed decision about Down syndrome screening. Implementation strategies will need to address these factors.

Mammography screening among Arab American women in metropolitan Detroit.

PubMed

Schwartz, Kendra; Fakhouri, Monty; Bartoces, Monina; Monsur, Joseph; Younis, Amani

2008-12-01

Mammography screening behavior has not been well studied among Middle Eastern immigrant women. We conducted a telephone survey of 365 Arab American women residing in metropolitan Detroit, home to one of the largest populations of Middle Eastern immigrants in the US, to determine prevalence of factors associated with mammography, and attitudes and beliefs regarding mammography screening. Of 365 participants, only five were born in the US. Mean age was 53.2 years (SD 10.8). Two hundred twelve (58.1%) reported having mammogram every 1-2 years; 70% ever had mammogram. Age 50-64 years, having health insurance, married status, being in the US over 10 years, and being Lebanese were associated with mammography every 1-2 years. After adjusting for demographic factors, perceived seriousness of disease, general health motivation, and having fewer barriers were associated with more frequent screening. Appropriate mammography screening is decreased in this group. Targeted outreach regarding screening is appropriate for this population; however, lack of insurance may prevent adequate follow-up.

Performance of the French version of the 4AT for screening the elderly for delirium in the emergency department.

PubMed

Gagné, Anne-Julie; Voyer, Philippe; Boucher, Valérie; Nadeau, Alexandra; Carmichael, Pierre-Hugues; Pelletier, Mathieu; Gouin, Emilie; Berthelot, Simon; Daoust, Raoul; Wilchesky, Machelle; Richard, Hélène; Pelletier, Isabelle; Ballard, Stephanie; Laguë, Antoine; Émond, Marcel

2018-05-17

CLINICIAN'S CAPSULE What is known about the topic? Delirium is frequent in older inpatients but often goes undetected. A short tool, the 4 A's Test (4AT), was created and validated for the detection of delirium. What did this study ask? This study compared the performance of the French version of the 4AT (4AT-F) with the Confusion Assessment Method (CAM) for the screening of delirium. What did this study find? The 4AT-F was a fast and reliable screening tool for delirium in the emergency department (ED). Why does this study matter to clinicians? Because of its quick administration time, it allows for systematic screening of patients at risk of delirium and cognitive impairment.

Self-efficacy and health behaviors toward the prevention of diabetes among high risk individuals living in Appalachia.

PubMed

Serrano, Elena; Leiferman, Jennifer; Dauber, Sarah

2007-04-01

Recent clinical trials indicate that type 2 diabetes can largely be prevented through lifestyle factors. In order to identify important modalities for the prevention of diabetes in medically underserved counties of Virginia (Appalachia), a questionnaire was administered to 135 at-risk individuals, having reported at least one risk factor for diabetes. The questionnaire assessed attitudes, self-efficacy, diet, and physical activity toward the prevention of type 2 diabetes. Overall, none of the respondents reported being told by a physician that they were at risk for diabetes. Overweight was the most frequently reported risk factor (87.0%), followed by physical inactivity (67.3%). More than one-third (38.9%) reported at least three diabetes symptoms. When stratified by low and high risk level, there were no significant differences in self-efficacy, control, and healthy dietary behaviors (p < .05). High risk individuals did report having lower rates of full health insurance coverage, being less active and running out of food more frequently than low risk individuals, however. The findings suggest that cost-effective prevention efforts should incorporate physician education, include screenings, and address self-efficacy enhancing strategies toward preventing type 2 diabetes.

Analysis of beta-lactam antibiotics in incurred raw milk by rapid test methods and liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

PubMed

Riediker, S; Diserens, J M; Stadler, R H

2001-09-01

A recently developed confirmatory LC-MS method has been applied to the quantification of five major beta-lactam antibiotics in suspect raw bovine milk samples that gave a positive response with receptor-based (BetaStar) and rapid microbial inhibitory screen tests (Delvotest SP). In total, 18 presumptive positive raw milk samples were reanalyzed; 16 samples showed traces of antibiotic residues that could be identified and quantified by the LC-MS method, ranging from the limits of confirmation up to 38 microg/kg. Of the positive samples, only five (approximately 30%) were found to be violative of EU maximum residue limits. The most frequently detected antibiotic residues were cloxacillin and penicillin G, the former often in combination with amoxicillin or ampicillin. This study compares the results obtained by the three methods on identical samples and addresses how these relate to certain criteria such as sensitivity and selectivity. Furthermore, the limitations of the LC-MS method and the potential impact of the presence of frequently more than one residue in the same milk sample on the response of the rapid test methods are discussed.

Nature of frequent deletions in CEBPA.

PubMed

Fuchs, Ota; Kostecka, Arnost; Provaznikova, Dana; Krasna, Blazena; Brezinova, Jana; Filkukova, Jitka; Kotlin, Roman; Kouba, Michal; Kobylka, Petr; Neuwirtova, Radana; Jonasova, Anna; Caniga, Miroslav; Schwarz, Jiri; Markova, Jana; Maaloufova, Jacqueline; Sponerova, Dana; Novakova, Ludmila; Cermak, Jaroslav

2009-01-01

C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.

Hit Dexter: A Machine-Learning Model for the Prediction of Frequent Hitters.

PubMed

Stork, Conrad; Wagner, Johannes; Friedrich, Nils-Ole; de Bruyn Kops, Christina; Šícho, Martin; Kirchmair, Johannes

2018-03-20

False-positive assay readouts caused by badly behaving compounds-frequent hitters, pan-assay interference compounds (PAINS), aggregators, and others-continue to pose a major challenge to experimental screening. There are only a few in silico methods that allow the prediction of such problematic compounds. We report the development of Hit Dexter, two extremely randomized trees classifiers for the prediction of compounds likely to trigger positive assay readouts either by true promiscuity or by assay interference. The models were trained on a well-prepared dataset extracted from the PubChem Bioassay database, consisting of approximately 311 000 compounds tested for activity on at least 50 proteins. Hit Dexter reached MCC and AUC values of up to 0.67 and 0.96 on an independent test set, respectively. The models are expected to be of high value, in particular to medicinal chemists and biochemists who can use Hit Dexter to identify compounds for which extra caution should be exercised with positive assay readouts. Hit Dexter is available as a free web service at http://hitdexter.zbh. uni-hamburg.de. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes.

PubMed

Sun, Feng; Zhang, Jun-Xiu; Yang, Chang-Yi; Gao, Guan-Qi; Zhu, Wen-Bin; Han, Bing; Zhang, Le-Le; Wan, Yue-Yue; Ye, Xiao-Ping; Ma, Yu-Ru; Zhang, Man-Man; Yang, Liu; Zhang, Qian-Yue; Liu, Wei; Guo, Cui-Cui; Chen, Gang; Zhao, Shuang-Xia; Song, Ke-Yi; Song, Huai-Dong

2018-06-01

Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited. One hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees. Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes ( DUOX2 , DUOXA2 , DUOXA1 , TG , TPO and TSHR ) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2 , DUOXA2 , TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes ( FOXE1 , NKX2-1 , PAX8 and HHEX ) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands. Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries. © 2018 The authors.

Assessing the influence of rater and subject characteristics on measures of agreement for ordinal ratings.

PubMed

Nelson, Kerrie P; Mitani, Aya A; Edwards, Don

2017-09-10

Widespread inconsistencies are commonly observed between physicians' ordinal classifications in screening tests results such as mammography. These discrepancies have motivated large-scale agreement studies where many raters contribute ratings. The primary goal of these studies is to identify factors related to physicians and patients' test results, which may lead to stronger consistency between raters' classifications. While ordered categorical scales are frequently used to classify screening test results, very few statistical approaches exist to model agreement between multiple raters. Here we develop a flexible and comprehensive approach to assess the influence of rater and subject characteristics on agreement between multiple raters' ordinal classifications in large-scale agreement studies. Our approach is based upon the class of generalized linear mixed models. Novel summary model-based measures are proposed to assess agreement between all, or a subgroup of raters, such as experienced physicians. Hypothesis tests are described to formally identify factors such as physicians' level of experience that play an important role in improving consistency of ratings between raters. We demonstrate how unique characteristics of individual raters can be assessed via conditional modes generated during the modeling process. Simulation studies are presented to demonstrate the performance of the proposed methods and summary measure of agreement. The methods are applied to a large-scale mammography agreement study to investigate the effects of rater and patient characteristics on the strength of agreement between radiologists. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Diagnostic accuracy of history and physical examination in bacterial acute rhinosinusitis.

PubMed

Autio, Timo J; Koskenkorva, Timo; Närkiö, Mervi; Leino, Tuomo K; Koivunen, Petri; Alho, Olli-Pekka

2015-07-01

To evaluate the diagnostic accuracy of symptoms, the symptom progression pattern, and clinical signs in identifying bacterial acute rhinosinusitis (ARS). We conducted an inception cohort study among 50 military recruits with ARS. We collected symptoms daily from the onset of symptoms to approximately 10 days. At 9 to 10 days, standardized data on symptoms and physical findings were gathered. A positive culture of maxillary sinus aspirate was considered to be the reference standard for bacterial ARS. At 9 to 10 days, the presence or deterioration after 5 days of any of the symptoms could not be used to diagnose bacterial ARS. Toothache had an adequate positive likelihood ratio (positive likelihood ratio [LR+] 4.4) but was too rare to be used for screening. In contrast, several physical findings at 9 to 10 days were of more diagnostic use and frequent enough for screening. Moderate or profuse (vs. none/minimal) amount of secretion in nasal passage seen in anterior rhinoscopy satisfactorily either ruled in, if present (LR+ 3.2), or ruled out, if absent (negative likelihood ratio 0.2), bacterial ARS. If any secretion was seen in the posterior pharynx or middle meatus, the probability of bacterial ARS increased markedly (LR+ 5.3 and LR+ 11.0, respectively). We found symptoms or their change to be of little use in identifying bacterial ARS. In contrast, we observed several clinical findings after 9 to 10 days of symptoms to predict bacterial ARS quite accurately. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Airway hyperreactivity in asymptomatic military personnel.

PubMed

Morris, Michael J; Schwartz, Darin S; Nohrenberg, Jana L; Dooley, Sean N

2007-11-01

Asthma is frequently diagnosed in military personnel despite strict guidelines that disqualify persons with active disease or a recent history of asthma. It is generally considered incompatible with military service, because of the regular physical training, outdoor training exercises, and deployments to remote locations. The objective of this study was to determine the prevalence of airway hyperreactivity in asymptomatic military personnel, as an estimate of subclinical reactive airway disease. A prospective study of healthy, asymptomatic, military personnel with no previous history of asthma and <1 year on active duty status was conducted. After completion of a screening questionnaire, personnel underwent baseline spirometry with a portable spirometer. Personnel with obstructive indices (based on published guidelines) and matched control subjects participated in an exercise test (1.5-mile run), with pre- and postexercise spirometry. A total of 222 asymptomatic military personnel completed baseline spirometry, and 31 (14%) were found have airway obstruction. A normal matched control group of 31 military personnel and 26 personnel with obstruction performed exercise spirometry. Twenty-three percent of the participants with obstruction demonstrated increased airway hyper-reactivity after exercise, based on a reduction in forced expiratory volume at 1 second, compared with 19% of control subjects. Asymptomatic airway obstruction has a prevalence of 14% in young military personnel. A significant percentage of individuals also have evidence of worsening obstruction during exercise. These data suggest that screening spirometry may identify early reactive airway disease in asymptomatic individuals and should be considered as a method to identify persons predisposed to developing symptomatic asthma.

Use of time-of-flight mass spectrometry for large screening of organic pollutants in surface waters and soils from a rice production area in Colombia.

PubMed

Hernández, F; Portolés, T; Ibáñez, M; Bustos-López, M C; Díaz, R; Botero-Coy, A M; Fuentes, C L; Peñuela, G

2012-11-15

The irrigate district of Usosaldaña, an important agricultural area in Colombia mainly devoted to rice crop production, is subjected to an intensive use of pesticides. Monitoring these compounds is necessary to know the impact of phytosanitary products in the different environmental compartments. In this work, surface water and soil samples from different sites of this area have been analyzed by applying an analytical methodology for large screening based on the use of time-of-flight mass spectrometry (TOF MS) hyphenated to liquid chromatography (LC) and gas chromatography (GC). Several pesticides were detected and unequivocally identified, such as the herbicides atrazine, diuron or clomazone. Some of their main metabolites and/or transformation products (TPs) like deethylatrazine (DEA), deisopropylatrazine (DIA) and 3,4-dichloroaniline were also identified in the samples. Among fungicides, carbendazim, azoxystrobin, propiconazole and epoxiconazole were the most frequently detected. Insecticides such as thiacloprid, or p,p'-DDT metabolites (p,p'-DDD and p,p'-DDE) were also found. Thanks to the accurate-mass full-spectrum acquisition in TOF MS it was feasible to widen the number of compounds to be investigated to other families of contaminants. This allowed the detection of emerging contaminants, such as the antioxidant 3,5-di-tertbutyl-4-hydroxy-toluene (BHT), its metabolite 3,5-di-tert-butyl-4-hydroxy-benzaldehyde (BHT-CHO), or the solar filter benzophenone, among others. Copyright © 2012 Elsevier B.V. All rights reserved.

The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing.

PubMed

Schrijver, Iris; Pique, Lynn; Graham, Steve; Pearl, Michelle; Cherry, Athena; Kharrazi, Martin

2016-01-01

Despite the implementation of cystic fibrosis (CF) newborn screening programs across the United States, the identification of CFTR gene variants in nonwhite populations compared with whites remains suboptimal. Our objective was to establish the spectrum of CFTR variants and their frequencies in CF patients in the United States with African, Native American, Asian, East Indian, or Middle Eastern backgrounds. By using direct DNA sequencing, we identified two CFTR variants in 89 of 140 affected nonwhite individuals with uncharacterized genotypes. Seven variants were novel. Multiplex ligation-dependent probe amplification detected 14 rearrangements in the remaining 51 patients, 6 of which were novel. Deletions and duplications accounted for 17% of unidentified alleles. A cross-sectional analysis of genotyping data from the CF Foundation Patient Registry was performed, comparing 3496 nonwhite patients with 22,206 white CF patients. Patients of Hispanic, black, or Asian ancestry were less likely to have two identified CFTR variants (P < 0.0001 for Hispanics and blacks, P = 0.003 for Asians), and more likely to carry no mutations on the commonly used 23 mutation carrier screening panel (P < 0.0001). We analyzed the mutations recorded for each ancestry and summarized the most frequent ones. This research could facilitate equity in mutation detection between white and nonwhite or mixed-ethnicity CF patients, enabling an earlier diagnosis improving their quality of life. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Needs of people with severe dementia at the end-of-life: a systematic review.

PubMed

Perrar, Klaus Maria; Schmidt, Holger; Eisenmann, Yvonne; Cremer, Bernadette; Voltz, Raymond

2015-01-01

Epidemiological data shows an increasing number of people affected by dementia. It is mentioned that people with severe dementia have special care needs which are intensified at the end-of-life. This paper offers a systematic analysis of the current status of research on the needs of people with severe dementia in the last phase of their lives. A systematic review of the MEDLINE, CINAHL, Cochrane Library, PsycINFO, and AMED databases performed up to April 2014 was further expanded by contacting experts, conducting internet searches, and screening relevant reference lists. Studies were screened according to defined criteria and appraised for methodological quality. Findings were then synthesized using a narrative thematic approach to identify and categorize relevant needs into thematic categories and subcategories. A total of ten studies published from 1993-2013 were identified, encompassing qualitative (n = 7), quantitative (n = 2), and a mixed-methods study (n = 1). Data synthesis yielded seven themes, with physical, social, and psychological needs the categories most frequently mentioned. Other categories were spiritual, supportive, and environmental needs and needs related to individuality. Needs were often named, but what they entailed operationally was not highlighted in detail. This systematic review shows the paucity of empirical findings on the needs of people with severe dementia. The structured presentation of thematic categories points to a clearer delineation of these needs. Thus, this overview emphasizes the topics for future research and can likewise serve as an orientation for care provision.

Comparison of characteristics between frequent participants and non-participants in screening program for stomach cancer.

PubMed

Fukao, A; Hisamichi, S; Komatsu, S; Shimizu, H; Satoh, H; Nakatsuka, H; Watanabe, T; Fujisaku, S; Ichinowatari, Y; Kuroda, S

1992-04-01

To clarify the differences in characteristics between participants and non-participants in the screening program for stomach cancer, life-style and medical histories were compared among 20, 169 subjects who lived in an urban area (Sendai) and a rural area (Wakuya and Tajiri) in Miyagi Prefecture, Japan. All subjects were classified into three groups according to the frequency of participation in the screening program during the last 5 years; i.e., frequent participating group (FPG) for 4 or 5 times, reference group (RG) for 1-3 times and non-participating group (NPG) for 0 times. Subjects in the FPG consumed more milk and green-yellow vegetable whereas those in the NPG consumed less these foods. The age-adjusted proportions of present smokers were higher in the NPG but lower in the FPG significantly. The proportions of subjects who had parental histories of all cancers and stomach cancer and past history of gastro-duodenal ulcer were higher in the FPG and lower in the NPG. To control influences among the variables a stepwise multiple regression analysis was done, and it revealed that smoking and parental history of cancers were strong predictors to explain the frequency of participation.

Foot-to-shoe mismatch and rates of referral in Special Olympics athletes.

PubMed

Jenkins, David W; Cooper, Kimbal; O'Connor, Rachel; Watanabe, Liane

2012-01-01

Improperly fitted shoes are frequently seen in athletes participating in Special Olympics competitions. This foot-to-shoe mismatch may result in deformities as well as discomfort and reduced performance or injuries in competitions. A primary purpose for providing medical screenings is to identify conditions unknown and to promptly refer to an appropriate provider for evaluation and care. This study attempts to determine the prevalence of improperly fitted shoes and the rate of referral for Special Olympics athletes screened at Fit Feet venues. To evaluate the foot-to-shoe mismatch and rate of referral, 4,094 Fit Feet screenings of Special Olympics athletes participating in US competitions in 2005 to 2009 were analyzed. The participants were 58.5% male and 41.5% female, with a median age of 25.6 years. A power analysis and the χ(2) test were used. The athletes voluntarily underwent a foot screening that followed the standardized Special Olympics Fit Feet protocol. The Brannock Device for measuring feet was used to assess proper fit. A proper fit was found in 58.56% of the athletes, with 28.60% wearing shoes too big and 12.84% wearing shoes too small. Unrelated to shoe fit, 20% of the athletes required referrals for professional follow-up based on abnormal clinical findings. There is a significant (41.44%) mismatch of foot to shoe in Special Olympics athletes. The most common mismatch is a shoe too big, with a much smaller number of athletes having shoes too small. Awareness of this foot-to-shoe incompatibility may be useful for the development of shoes better designed for athletes with a foot structure not consistent with conventional shoes. Because 20% of the athletes required a referral for professional follow-up, Fit Feet examinations are important for identifying athletes with conditions that can be more readily evaluated and treated, thus improving the athletes' comfort and performance. Beyond knowing the rate of referral, future studies can determine the conditions or findings that necessitate a referral and the ultimate outcome of that referral.

Nursing Minimum Data Sets for documenting nutritional care for adults in primary healthcare: a scoping review.

PubMed

Håkonsen, Sasja Jul; Pedersen, Preben Ulrich; Bjerrum, Merete; Bygholm, Ann; Peters, Micah D J

2018-01-01

To identify all published nutritional screening instruments that have been validated in the adult population in primary healthcare settings and to report on their psychometric validity. Within health care, there is an urgent need for the systematic collection of nursing care data in order to make visible what nurses do and to facilitate comparison, quality assurance, management, research and funding of nursing care. To be effective, nursing records should accurately and comprehensively document all required information to support safe and high quality care of patients. However, this process of documentation has been criticized from many perspectives as being highly inadequate. A Nursing Minimum Data Set within the nutritional area in primary health care could therefore be beneficial in order to support nurses in their daily documentation and observation of patients. The review considered studies that included adults aged over 18 years of any gender, culture, diagnosis and ethnicity, as well as nutritional experts, patients and their relatives. The concepts of interest were: the nature and content of any nutritional screening tools validated (regardless of the type of validation) in the adult population in primary healthcare; and the views and opinions of eligible participants regarding the appropriateness of nutritional assessment were the concept of interest. Studies included must have been conducted in primary healthcare settings, both within home care and nursing home facilities. This scoping review used a two-step approach as a preliminary step to the subsequent development of a Nursing Minimum Data Set within the nutritional area in primary healthcare: i) a systematic literature search of existing nutritional screening tools validated in primary health care; and ii) a systematic literature search on nutritional experts opinions on the assessment of nutritional nursing care of adults in primary healthcare as well as the views of patients and their relatives. Multiple databases (PubMed, CINAHL, Embase, Scopus, Swemed+, MedNar, CDC, MEDION, Health Technology Assessment Database, TRIP database, NTIS, ProQuest Dissertations and Theses, Google Scholar, Current Contents) were searched from their inception to September 2016. The results from the studies were extracted using pre-developed extraction tools to all three questions, and have been presented narratively and by using figures to support the text. Twenty-nine nutritional screening tools that were validated within a primary care setting, and two documents on consensus statements regarding expert opinion were identified. No studies on the patients or relatives views were identified. The nutritional screening instruments have solely been validated in an over-55 population. Construct validity was the type of validation most frequently used in the validation process covering a total of 25 of the 29 tools. Two studies were identified in relation to the third review question. These two documents are both consensus statement documents developed by experts within the geriatric and nutritional care field. Overall, experts find it appropriate to: i) conduct a comprehensive geriatric assessment, ii) use a validated nutritional screening instrument, and iii) conduct a history and clinical diagnosis, physical examination and dietary assessment when assessing primarily the elderly's nutritional status in primary health care.

Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

PubMed

Mainguy, Catherine; Bellon, Gabriel; Delaup, Véronique; Ginoux, Tiphanie; Kassai-Koupai, Behrouz; Mazur, Stéphane; Rabilloud, Muriel; Remontet, Laurent; Reix, Philippe

2017-01-01

Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF. Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of β-cell function (HOMA-%B) and glycated haemoglobin A1C. Patients were classified into three groups according to CGMS: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM). Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)]. OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.

Pre-screening method for somatic cell contamination in human sperm epigenetic studies.

PubMed

Jenkins, Timothy G; Liu, Lihua; Aston, Kenneth I; Carrell, Douglas T

2018-04-01

Sperm epigenetic profiles are frequently studied and are of great interest in many fields. One major technical concern when assessing these marks is the potential for somatic cell contamination. Because somatic cells have dramatically different epigenetic signatures, even small levels of contamination can result in significant problems in analysis and interpretation of data. In this study we evaluate an assay, which we designed to offer a reliable 'pre-screen' for somatic cell contamination that directly assesses the DNA being used in the study to determine tissue purity. In brief, we designed an inexpensive and simple assay that utilizes the strong differential methylation between sperm and somatic cells at four genomic loci to assess the general purity of samples prior to performing expensive and time intensive assays. The assay is able to reliably detect contamination qualitatively by running the sample on an agarose gel, or quantitatively with the use of a bioanalyzer. With this technique we have found that we can detect potentially contaminating signals in samples of many different types, including those from patients with poor sperm phenotypes (oligozoospermia, asthenozoospermia, and teratozoospermia). We also have found that the use of multiple sites to determine potential contamination is key, as some conditions (asthenozoospermia specifically) appear at one site to reflect a somatic-like profile, while at all other sites it appears to have very typical sperm DNA methylation signatures. Taken together, the use of the assay described herein was effective at identifying contamination and could be implemented in many labs to quickly and inexpensively pre-screen samples prior to performing far more expensive and labor intensive procedures. Additionally, the principles applied to the development of this assay could be easily adapted for the development of other assays to pre-screen different tissue/cell types or model organisms.

Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes.

PubMed

García-Castillo, Herbert; Vásquez-Velásquez, Ana Isabel; Rivera, Horacio; Barros-Núñez, Patricio

2008-07-01

Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive syndrome related to BUB1B gene mutations and characterized by multiple mosaic aneuploidies, cancer predisposition, and a distinct phenotype. We report on two mildly affected sibs with MVA syndrome but without BUB1B mutation. Both patients exhibited growth retardation, frontal bossing, triangular face and micrognathia but not microcephaly or cancer. Aneuploidies were assessed both in G-banded metaphases from lymphocyte cultures and in interphase nuclei from buccal cells by FISH. Screening of 23 exons and intron-exon boundaries of BUB1B was also carried out. These patients were then compared with other 19 MVA patients screened for BUB1B mutations. Around one half of the cultured lymphocytes from our patients had aneuploidies ranging from nullisomies to heptasomies; the most frequent abnormalities were trisomies (42%) and monosomies (28%). FISH results demonstrated more chromosomal losses than gains. Screening of BUB1B in our two patients failed to identify any mutation. A review of the 21/35 patients screened for BUB1B demonstrated three clinical pictures. Patients with monoallelic BUB1B mutations were severely affected with Dandy-Walker complex (7/8), cataracts (6/6), and Wilms' tumor (7/8); premature chromatid separation (PCS) was observed in 8/8 propositi and 7/7 carrier parents. Patients without BUB1B mutations were mildly affected with no evidence of cancer, Dandy-Walker malformation or cataract, and rarely (1/7) showed PCS. Finally, patients with biallelic BUB1B mutations showed a moderate phenotype. The distinct MVA clinical groups delineated here point to involvement of at least another mitotic spindle checkpoint gene in addition to the BUB1B gene. (c) 2008 Wiley-Liss, Inc.