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Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review  

PubMed Central

Background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. Methods: Systematic review of the literature and narrative synthesis. Results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. Conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers. PMID:25734382

Neal, R D; Tharmanathan, P; France, B; Din, N U; Cotton, S; Fallon-Ferguson, J; Hamilton, W; Hendry, A; Hendry, M; Lewis, R; Macleod, U; Mitchell, E D; Pickett, M; Rai, T; Shaw, K; Stuart, N; Tørring, M L; Wilkinson, C; Williams, B; Williams, N; Emery, J



Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression.  


Regions of the medial visceromotor network (MVN) participate in concurrently regulating shifts in both affective state and cardiac vagal control in the attentional background, and this regulatory ability may be impaired in depression. We examined whether the relationship between changes in BOLD within MVN regions and changes in cardiac vagal control (VC) during affective state shifting changed with depression treatment. Ten depressed and ten control subjects performed an emotional counting Stroop task designed to trigger affective change in the attentional background while undergoing functional magnetic resonance imaging and concurrent electrocardiography (ECG) on four occasions: week 0 (pre-treatment) and weeks 2, 6 and 12 of treatment on sertraline. We measured the absolute value of change between adjacent emotional and neutral conditions in both VC and the BOLD signal in specific regions of the MVN. Over time consistent increases were observed in BOLD-VC magnitude correlations in depressed subjects in subgenual ACC and left DLPFC, which strongly correlated with depressive symptom improvement. Symptom improvement over time was also associated with decreases in the magnitude of both BOLD shifts and VC shifts within-subjects. This suggests that as depressive symptoms improve on sertraline, subgenual ACC and DLPFC may more efficiently regulate visceral states during affective state shifting. PMID:25282511

Smith, Ryan; Allen, John J B; Thayer, Julian F; Fort, Carolyn; Lane, Richard D



Evaluation of the Implementation of a Rapid Response Treatment Protocol for Patients with Acute Onset Stroke: Can We Increase the Number of Patients Treated and Shorten the Time Needed?  

PubMed Central

Aims This study aims to evaluate the implementation of a rapid response treatment protocol for patients presenting with acute onset ischemic stroke. Improvements of routines surrounding the admission and treatment of patients with intravenous thrombolysis (IVT), such as door-to-needle (DTN) times, and increasing the numbers of patients treated are discussed. Methods We conducted a retrospective analysis of all patients (n = 320) treated with IVT for acute onset ischemic stroke at the Stavanger University Hospital, Norway, between 2003 and 2012. In 2009, a succession of changes to pre- and intra-hospital routines were made as well as an improvement in the education of primary health care physicians, nurses and paramedics involved in the treatment of acute onset stroke patients (rapid response treatment protocol). Analyses of DTN times, onset-to-needle times and the number of patients treated per year were carried out to ascertain the effect of the changes made. The primary aim was to analyze DTN times to look for any changes, and the secondary aim was to analyze changes in the number of patients treated per year. Results In the years after the implementation of the rapid treatment protocol, we saw an improvement in the median DTN time with a decrease from 73 to 50 min in the first year (p = 0.03), a decrease of 45 min in the second year (p = 0.01) and a decrease of 31 min in the third year (p < 0.001). Similarly, an improvement in the number of patients treated per year was seen after enhancements in the treatment chain were made. A significant, 27-fold increase was shown when the number of patients treated in 2012 was compared with all patients treated in all years prior to the implementation of the rapid treatment protocol. Conclusions The implementation of the rapid treatment protocol for acute onset ischemic stroke patients led to a significant decrease in the DTN time at our center. These improvements also produced an increase in the number of patients treated per year. The extension of the therapeutic window from 3 to 4.5 h for the use of intravenous recombinant tissue plasminogen activator also played a role in the increased treatment numbers. PMID:25076956

Advani, Rajiv; Naess, Halvor; Kurz, Martin W.



Improvement of grafted watermelon transplant survival as a result of size and starch increases over time caused by rootstock fatty alcohol treatment Part II  

Technology Transfer Automated Retrieval System (TEKTRAN)

Fatty alcohol treatments can be used to eliminate the meristem of cucurbit (Family Cucurbitaceae) rootstocks which prevents regrowth when grafting, but the effects of the treatment on the rootstock have not been documented. Two rootstock types, ‘Emphasis’ bottle gourd (Lagenaria siceraria) and ‘Car...


Circadian Timing in Cancer Treatments  

E-print Network

Circadian Timing in Cancer Treatments Francis L´evi,1,2,3 Alper Okyar,1,4 Sandrine Dulong,1, systems biology, personalized medicine Abstract The circadian timing system is composed of molecular repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous

Clairambault, Jean


Increasing transmission capacity by real time monitoring  

Microsoft Academic Search

Real time monitoring of the thermal capability of transmission lines can typically increase the line capability by 10-30%. This additional capability can be achieved with a typical cost of $80000-$120000 per circuit, which is generally a small fraction of a cost of a new line or a major physical upgrade. It thus appears clear that real time thermal rating could

Tapani O. Seppa



Burns treatment in ancient times.  


Discovery of fire at the dawn of prehistoric time brought not only the benefits to human beings offering the light and heat, but also misfortune due to burns; and that was the beginning of burns treatment. Egyptian doctors made medicines from plants, animal products and minerals, which they combined with magic and religious procedures. The earliest records described burns dressings with milk from mothers of male babies. Goddess Isis was called upon to help. Some remedies and procedures proved so successful that their application continued for centuries. The Edwin Smith papyrus (1500 BC) mentioned the treatment of burns with honey and grease. Ebers Papyrus (1500 BC) contains descriptions of application of mud, excrement, oil and plant extracts. They also used honey, Aloe and tannic acid to heal burns. Ancient Egyptians did not know about microorganisms but they knew that honey, moldy bread and copper salts could prevent infections from dirt in burns healing. Thyme, opium and belladona were used for pain relief. In the 4th century BC, Hippocrates recorded that Greek and Roman doctors used rendered pig fat, resin and bitumen to treat burns. Mixture of honey and bran, or lotion of wine and myrrh were used by Celsus. Honey was also known in Ayurveda (Indian medicine) time. Ayurvedic records Characa and Sushruta included honey in their dressing aids to purify sores and promote the healing. Burn treatment in Chinese medicine was traditional. It was a compilation of philosophy, knowledge and herbal medicine. The successful treatment of burns started in recent time and it has been made possible by better knowledge of the pathophysiology of thermal injuries and their consequences, medical technology advances and improved surgical techniques. PMID:23888738

Pe?anac, Marija; Janji?, Zlata; Komarcevi?, Aleksandar; Paji?, Milos; Dobanovacki, Dusanka; Miskovi?, Sanja Skeledzija



Can increasing adult vaccination rates reduce lost time and increase productivity?  


This article addresses limited vaccination coverage by providing an overview of the epidemiology of influenza, pertussis, and pneumonia, and the impact these diseases have on work attendance for the worker, the worker's family, and employer profit. Studies focused on the cost of vaccination programs, lost work time, lost employee productivity and acute disease treatment are discussed, as well as strategies for increasing vaccination coverage to reduce overall health care costs for employers. Communicating the benefits of universal vaccination for employees and their families and combating vaccine misinformation among employees are outlined. [Workplace Health Saf 2014;62(12):508-515.]. PMID:25216055

Rittle, Chad



An investigation of productivity increases from hydraulic fracturing treatments  

E-print Network

AN INVESTIGATION OF PRODUCTIVITY INCREASES FROM HYDRAULIC FRACTURING TREATMENTS A Thesis b7 Robert Joe Boriskie Submitted to the Graduate School of the Agricultural and Mechanical College of Texas in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August, 1963 Major Subject: Petroleum Engineering AN INVESTIGATION OF PRODUCTIVITY INCREASES FROM HYDRAULIC FRACTURING TREATMENTS A Thesis Robert Joe Boriskie Approved as to style and content by: Chairman of Committee...

Boriskie, Robert Joe



Time to Eat: Household Production under Increasing Income Inequality  

Microsoft Academic Search

Using time diaries and expenditure data for the United States for 1985 and 2003, I examine how income and time prices affect time and goods inputs into eating. Both inputs increase with income, and higher time prices reduce time inputs. Between 1985 and 2003 the goods intensity of eating increased, especially lower in the income distribution, and average time inputs

Daniel S. Hamermesh



Is the Timing of Treatment Critical?  

Microsoft Academic Search

The timing of treatment for any condition is dependent on the underlying pathophysiology. One of the issues to consider is whether decreasing the time to intervention can be translated into recognisable benefits. Key data have been generated over the last 10 years which are relevant to the treatment of acute myocardial infarction (MI), including results of the large-scale ‘mega-trials’ in

Gianni Tognoni



Elimination of African Onchocerciasis: Modeling the Impact of Increasing the Frequency of Ivermectin Mass Treatment  

PubMed Central

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently. PMID:25545677

Coffeng, Luc E.; Stolk, Wilma A.; Hoerauf, Achim; Habbema, Dik; Bakker, Roel; Hopkins, Adrian D.; de Vlas, Sake J.



Increases in body mass index following initiation of methadone treatment.  


Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ?6months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8±0.95years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (p<0.001). Mean BMIs increased from 27.2±6.8 to 30.1±7.7kg/m(2), translating to a 17.8-pound increase (10% increase in body weight) in the overall patient sample. Gender was the strongest predictor of BMI changes (p<0.001), with significantly greater BMI increases in females than males (5.2 vs. 1.7kg/m(2), respectively). This translates to a 28-pound (17.5%) increase in females vs. a 12-pound (6.4%) increase in males. In summary, methadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally. PMID:25441923

Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C



Long term myriocin treatment increases MRP1 transport activity.  


We investigated the effect of myriocin treatment, which extensively depletes sphingolipids from cells, on multidrug resistance-related protein 1 (MRP1) efflux activity in MRP1 expressing cells and isolated plasma membrane vesicles. Our data reveal that both short term (3 days) and long term (7 days) treatment effectively reduce the cellular sphingolipid content to the same level. Intriguingly, a two-fold increase in MRP1-mediated efflux activity was observed following long term treatment, while short term treatment had no impact. Very similar data were obtained with plasma membrane vesicles isolated from myriocin-treated cells. Exploiting the cell-free vesicle system, Michaelis-Menten analysis revealed that the intrinsic MRP1 activity remained unaltered; however, the fraction of active transporter molecules increased. We demonstrate that the latter effect is due to an enhanced recruitment of MRP1 into lipid raft fractions, thereby promoting MRP1 activity. PMID:23178537

Meszaros, Peter; Klappe, Karin; van Dam, Annie; Ivanova, Pavlina T; Milne, Stephen B; Myers, David S; Brown, H Alex; Permentier, Hjalmar; Hoekstra, Dick; Kok, Jan W



Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus  

Microsoft Academic Search

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number

Jessica E. Malberg; Amelia J. Eisch; Eric J. Nestler; Ronald S. Duman



Increased risk of suicide under intrathecal ziconotide treatment? - a warning.  


Despite some other known psychiatric adverse effects, ziconotide is recommended for intrathecal pain treatment with a good efficacy and safety. Although some hints in previous studies are apparent, a higher suicidality has not been accepted as a treatment risk of ziconotide treatment by the investigators in the former randomized controlled trials so far. We present two cases supporting the suspicion of ziconotide-induced suicidality. Both showed no depressive symptoms at the time of treatment initiation. One patient performed suicide under low-dose (cumulative dosage: 779?g) 4 weeks after the onset of intrathecal ziconotide treatment despite sufficient pain relief. Another female patient with a history of depression, but free of symptoms under antidepressive medication since more than 15 years, developed severe suicidal ideation 2 months after ziconotide treatment (cumulative dosage: about 2900?g) with rapid recovery after drug discontinuation. The patient, who has completed suicide, had earlier given rise to discuss a potential depressive disorder, however, this diagnosis was scrapped, but the second patient had a clear history of depression. These cases substantiate the suspicion of a causal relationship between ziconotide and suicidality even in symptom-free patients with a history of depression. Therefore, a comprehensive psychiatric evaluation is unavoidable before and during ziconotide treatment. PMID:21041028

Maier, Christoph; Gockel, Hans-Helmut; Gruhn, Kai; Krumova, Elena K; Edel, Marc-Andreas



Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods  


Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900 to 1,000 C for 20 minutes to six hours.

Verhoeven, J.D.; McMasters, O.D.



Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods  


Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their Magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from to C. for 20 minutes to six hours.

Verhoeven, John D. (Ames, IA); McMasters, O. D. (Ames, IA)



Reconsidering the Temporal Increase in Fathers’ Time with Children  

Microsoft Academic Search

Using the 1977 Quality of Employment Survey and the 1997 National Study of the Changing Workforce this study showed that the temporal increase in fathers’ time with children was three times larger on non-workdays than workdays.\\u000a Multivariate analyses revealed that both work (e.g., job autonomy) and family (presence of young children, dependence on wives’\\u000a earnings) factors increased men’s time with

David J. Maume



Increasing rates of surgical treatment and preventing comorbidities may increase breast cancer survival for Aboriginal women  

PubMed Central

Background Lower breast cancer survival has been reported for Australian Aboriginal women compared to non-Aboriginal women, however the reasons for this disparity have not been fully explored. We compared the surgical treatment and survival of Aboriginal and non-Aboriginal women diagnosed with breast cancer in New South Wales (NSW), Australia. Methods We analysed NSW cancer registry records of breast cancers diagnosed in 2001–2007, linked to hospital inpatient episodes and deaths. We used unconditional logistic regression to compare the odds of Aboriginal and non-Aboriginal women receiving surgical treatment. Breast cancer-specific survival was examined using cumulative mortality curves and Cox proportional hazards regression models. Results Of the 27 850 eligible women, 288 (1.03%) identified as Aboriginal. The Aboriginal women were younger and more likely to have advanced spread of disease when diagnosed than non-Aboriginal women. Aboriginal women were less likely than non-Aboriginal women to receive surgical treatment (odds ratio 0.59, 95% confidence interval (CI) 0.42-0.86). The five-year crude breast cancer-specific mortality was 6.1% higher for Aboriginal women (17.7%, 95% CI 12.9-23.2) compared with non-Aboriginal women (11.6%, 95% CI 11.2-12.0). After accounting for differences in age at diagnosis, year of diagnosis, spread of disease and surgical treatment received the risk of death from breast cancer was 39% higher in Aboriginal women (HR 1.39, 95% CI 1.01-1.86). Finally after also accounting for differences in comorbidities, socioeconomic disadvantage and place of residence the hazard ratio was reduced to 1.30 (95% CI 0.94-1.75). Conclusion Preventing comorbidities and increasing rates of surgical treatment may increase breast cancer survival for NSW Aboriginal women. PMID:24606675



Model Predictive Control of HIFU Treatments in 3D for Treatment Time Reduction  

NASA Astrophysics Data System (ADS)

A real time model predictive feedback controller has been integrated with a combined Magnetic Resonance (MR) scanner and 256-element ultrasound phased array system to improve High Intensity Focused Ultrasound (HIFU) treatments. The objective of this research is to use a model based feedback controller to improve the quality of HIFU treatments by adjusting the power, heating time and cooling time of each applied pulse based on the measured MR temperatures. A prototype controller has been evaluated in simulations and agar phantom experiments. The results demonstrate the feasibility of the proposed real time MR control, including a 65% reduction in treatment time, and increase dose uniformity in the treatment volume with all normal tissue safety constraints satisfied.

Blankespoor, A.; Payne, A.; Todd, N.; Skliar, M.; Roell, S.; Roland, J.; Parker, D.; Roemer, R.



Increased Breastfeeding Rates in Black Women After a Treatment Intervention  

PubMed Central

Abstract There has been a considerable increase in rates of breastfeeding in the United States. Despite these trends, black women continue to fall below medical recommendations. Impoverished and poorly educated women also have a comparatively lower rate of breastfeeding. Provider encouragement and supportive interventions increase breastfeeding initiation among women of all backgrounds. The data presented come from a three-site randomized controlled bilingual depression treatment trial from 2005 to 2011 that examined the comparative effectiveness of interpersonal psychotherapy and a parenting education program. Breastfeeding education and support were provided for the majority of participants in each intervention. Breastfeeding status was queried at postpartum week 4. We found higher rates of breastfeeding in black women compared with those reported in national surveys. The black breastfeeding rate did not significantly differ from that of white or Hispanic women. American-born black women were just as likely to breastfeed as American-born white women, both at significantly greater rates than American-born Hispanic women. We also found no differences in breastfeeding rate in poorly educated and impoverished women. These data must be seen against the backdrop of a significant intervention to treat depression. Because breastfeeding interventions have been shown to increase breastfeeding rates, the support provided in our study likely increased rates in groups that lag behind. PMID:23971683

Endicott, Jean; Goetz, Raymond R.



Sources of increased timing variability following TMS over motor cortex  

E-print Network

Sources of increased timing variability following TMS over motor cortex Talia Konkle, Tim Verstynen-random order t 14 pacer tones14 pacer tones 47 total keypresses, 33 unpaced 7-10 TMS pulses7-10 TMS pulses - TMS over M1 selectively increases peripheral noise estimates. - The response delays are correlated

Oliva, Aude


Combined ultrasonication and thermal pre-treatment of sewage sludge for increasing methane production.  


This article focuses on the combination of ultrasonic and thermal treatment of sewage sludge (SS). The combination involved ultrasonicating a fraction of the sludge and thermal treatment at various temperatures and this resulted in solubilization of proteins and carbohydrates, and so contributing to increased COD solubilization. During the treatment, SCOD, soluble proteins and carbohydrates increased from 760 mg L(-1) to 10,200 mg L(-1), 110 mg L(-1) to 2,900 mg L(-1) and 60 mg L(-1) to 630 mg L(-1), respectively. It was found ultrasonication of only a fraction of the sludge (>20%) followed by thermal treatment led to significant improvement compared to thermal and ULS treatments applied on their own. At 65°C, the kinetic of solubilization was improved and the hyper-thermophilic treatment time could be reduced to a few hours when ultrasonication was used first. A linear correlation (R(2) = 95%) was found between the SCOD obtained after ultrasonication pre-treatment and anaerobic biodegradability. The combined treatment resulted in 20% increase in biogas production during the anaerobic digestion of the pre-treated sludge. PMID:25560267

Trzcinski, Antoine Prandota; Tian, Xinbo; Wang, Chong; Lin, Li Leonard; Ng, Wun Jern



Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers  

PubMed Central

Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. PMID:25750528

Ishioka, Masamichi; Yasui-Furukori, Norio; Sugawara, Norio; Furukori, Hanako; Kudo, Shuhei; Nakamura, Kazuhiko



Mindfulness meditation and relaxation training increases time sensitivity.  


Two experiments examined the effect of mindfulness meditation and relaxation on time perception using a temporal bisection task. In Experiment 1, the participants performed a temporal task before and after exercises of mindfulness meditation or relaxation. In Experiment 2, the procedure was similar than that used in Experiment 1, except that the participants were trained to mediate or relax every day over a period of several weeks. The results showed that mindfulness meditation exercises increased sensitivity to time and lengthened perceived time. However, this temporal improvement with meditation exercises was primarily observed in the experienced meditators. Our results also showed the experienced meditators were less anxious than the novice participants, and that the sensitivity to time increased when the level of anxiety decreased. Our results were explained by the practice of mindfulness technique that had developed individuals' abilities in devoting more attention resources to temporal information processing. PMID:25460243

Droit-Volet, S; Fanget, M; Dambrun, M



Increased risk of suicide under intrathecal ziconotide treatment? – A warning  

Microsoft Academic Search

Despite some other known psychiatric adverse effects, ziconotide is recommended for intrathecal pain treatment with a good efficacy and safety. Although some hints in previous studies are apparent, a higher suicidality has not been accepted as a treatment risk of ziconotide treatment by the investigators in the former randomized controlled trials so far. We present two cases supporting the suspicion

Christoph Maier; Hans-Helmut Gockel; Kai Gruhn; Elena K. Krumova; Marc-Andreas Edel



Cigarette Smoking Increases the Risk of Root Canal Treatment  

Microsoft Academic Search

Few studies have investigated smoking as a risk factor for root canal treatment. We studied the effect of smoking on the incidence of root canal treatment, controlling for recognized risk factors, in 811 dentate male participants in the VA Dental Longitudinal Study. Participants were not VA patients. Follow-up ranged from 2 to 28 years. Root canal treatment was verified on

E. A. Krall; C. Abreu Sosa; C. Garcia; M. E. Nunn; D. J. Caplan; R. I. Garcia



Method for Predicting Which Customers' Time Deposit Balances Will Increase  

NASA Astrophysics Data System (ADS)

This paper proposes a method of predicting which customers' account balances will increase by using data mining to effectively and efficiently promote sales. Prediction by mining all the data in a business is difficult because of much time required to collect, process, and calculate it. The selection of which features are used for prediction is a critical issue. We propose a method of selecting features to improve the accuracy of prediction within practical time limits. It consists of three parts: (1) converting collected features into financial behavior features that reflect customer actions, (2) extracting features affecting increases in account balances from these collected and financial behavior features, and (3) predicting customers whose account balances will increase based on the extracted features. We found the accuracy of prediction in an experiment with our method to be higher than with other conventional methods.

Ono, Toshiyuki; Yoshikawa, Hiroshi; Morita, Masahiro; Komoda, Norihisa


Time Pressure Increases Cooperation in Competitively Framed Social Dilemmas  

PubMed Central

What makes people willing to pay costs to benefit others? Does such cooperation require effortful self-control, or do automatic, intuitive processes favor cooperation? Time pressure has been shown to increase cooperative behavior in Public Goods Games, implying a predisposition towards cooperation. Consistent with the hypothesis that this predisposition results from the fact that cooperation is typically advantageous outside the lab, it has further been shown that the time pressure effect is undermined by prior experience playing lab games (where selfishness is the more advantageous strategy). Furthermore, a recent study found that time pressure increases cooperation even in a game framed as a competition, suggesting that the time pressure effect is not the result of social norm compliance. Here, we successfully replicate these findings, again observing a positive effect of time pressure on cooperation in a competitively framed game, but not when using the standard cooperative framing. These results suggest that participants' intuitions favor cooperation rather than norm compliance, and also that simply changing the framing of the Public Goods Game is enough to make it appear novel to participants and thus to restore the time pressure effect. PMID:25551386

Cone, Jeremy; Rand, David G.



Treatment of chronic insomnia by restriction of time in bed.  


A treatment of chronic insomnia is described that is based on the recognition that excessive time spent in bed is one of the important factors that perpetuates insomnia. Thirty-five patients, with a mean age of 46 years and a mean history of insomnia of 15.4 years, were treated initially by marked restriction of time available for sleep, followed by an extension of time in bed contingent upon improved sleep efficiency. At the end of the 8-week treatment program, patients reported an increase in total sleep time (p less than 0.05) as well as improvement in sleep latency, total wake time, sleep efficiency, and subjective assessment of their insomnia (all p less than 0.0001). Improvement remained significant for all sleep parameters at a mean of 36 weeks after treatment in 23 subjects participating in a follow-up assessment. Although compliance with the restricted schedule is difficult for some patients, sleep restriction therapy is an effective treatment for common forms of chronic insomnia. PMID:3563247

Spielman, A J; Saskin, P; Thorpy, M J



Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments  

NASA Astrophysics Data System (ADS)

In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (? = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.

Herrmann, Katharina; Flöhr, Christian; Stalljohann, Jens; Apiou-Sbirlea, Gabriela; Kandulla, Jochen; Birngruber, Reginald; Brinkmann, Ralf



Using wastewater for cooling: Increasing water reuse poses treatment challenges  

SciTech Connect

Technologies for control of biofouling, scale, corrosion and microbiologically influenced corrosion (MIC) in cooling water systems are discussed. Techniques involving water reuse and using wastewater as makeup are emphasized, and associated problems are identified. Appropriate chemical treatments, including biocides and biostats, biodispersants, sludge dispersants, corrosion inhibitors, and supplementary chemical treatments, are outlined. New and developing technologies reviewed include microorganism control based on biodispersants and on enzymes.

Lutey, R.W. [Buckman Labs. International Inc., Memphis, TN (United States)



Phosphodiesterase type 5 inhibitor Tadalafil increases Rituximab treatment efficacy in a mouse brain lymphoma model.  


The treatment efficacy of Rituximab on lymphoma as an immunotherapeutic approach is confirmed, but this treatment has limited penetration through the brain micro vessels. Such limitation significantly attenuates the efficacy of systemic administration of this antibody on brain lymphomas. We aimed to confirm that Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, could increase microvascular permeability and Rituximab treatment efficacy in brain lymphomas. We established a mouse brain lymphoma model by planting human-derived lymphoma cell line Raji into brain parenchyma of mice using stereotaxic techniques. After 16 days, 7.0 T magnetic resonance imaging was performed to confirm the presence of the mass. The mice were observed under near-infrared fluorescence after intravenous injection of fluorescence-labeled Rituximab. Evans Blue was used as probe to detect the microvascular permeability of brain lymphomas after Tadalafil administration. Starting from 4 days after implantation, the mice were administered different treatments. Survival analysis of brain lymphoma-loaded mice was performed. Evans Blue detection showed that Tadalafil administration could increase brain vascular permeability in the tumor-bearing group compared with control mice. Rituximab treatment prolonged the survival time of mice compared with the untreated control group (mean 25.75 vs. 20.8 days, p < 0.05). Tadalafil with Rituximab treatment resulted in the longest survival time (29 days, p < 0.05). Rituximab may be a promising therapeutic agent for the treatment of brain lymphoma. Tadalafil can enhance Rituximab treatment efficacy by improving the microvascular permeability in mice brain lymphoma. PMID:25524816

Wang, Rong; Chen, Wenli; Zhang, Qiang; Liu, Yong; Qiao, Xiaoyun; Meng, Kui; Mao, Ying



This is an exciting time in the treatment of lymphoma.  


... Cover Story: Leukemia/Lymphoma "This is an exciting time in the treatment of lymphoma." Past Issues / Summer ... best medication for each patient, indicates the best time for treatments, and sheds light on the patient's ...


Focus on Increasing Treatment Self-Efficacy to Improve Human Immunodeficiency Virus Treatment Adherence  

PubMed Central

Purpose Human immunodeficiency virus (HIV) treatment self-efficacy is the confidence held by an individual in her or his ability to follow treatment recommendations, including specific HIV care such as initiating and adhering to antiretroviral therapy (ART). The purpose of this study was to explore the potential mediating role of treatment adherence self-efficacy in the relationships between Social Cognitive Theory constructs and self- reported ART adherence. Design Cross-sectional and descriptive. The study was conducted between 2009 and 2011 and included 1,414 participants who lived in the United States or Puerto Rico and were taking antiretroviral medications. Methods Social cognitive constructs were tested specifically: behaviors (three adherence measures each consisting of one item about adherence at 3-day and 30-day along with the adherence rating scale), cognitive or personal factors (the Center for Epidemiology Studies Depression Scale to assess for depressive symptoms, the 12-Item Short Form Health Survey (SF-12) to assess physical functioning, one item about physical condition, one item about comorbidity), environmental influences (the Social Capital Scale, one item about social support), and treatment self-efficacy (HIV Adherence Self-Efficacy Scale). Analysis included descriptive statistics and regression. Results The average participant was 47 years old, male, and a racial or ethnic minority, had an education of high school or less, had barely adequate or totally inadequate income, did not work, had health insurance, and was living with HIV/acquired immunodeficiency syndrome for 15 years. The model provided support for adherence self-efficacy as a robust predictor of ART adherence behavior, serving a partial mediating role between environmental influences and cognitive or personal factors. Conclusions Although other factors such as depressive symptoms and lack of social capital impact adherence to ART, nurses can focus on increasing treatment self-efficacy through diverse interactional strategies using principles of adult learning and strategies to improve health literacy. Clinical Relevance Adherence to ART reduces the viral load thereby decreasing morbidity and mortality and risk of transmission to uninfected persons. Nurses need to use a variety of strategies to increase treatment self-efficacy. PMID:23121723

Nokes, Kathleen; Johnson, Mallory O.; Webel, Allison; Rose, Carol Dawson; Phillips, J. Craig; Sullivan, Kathleen; Tyer-Viola, Lynda; Rivero-Méndez, Marta; Nicholas, Patrice; Kemppainen, Jeanne; Sefcik, Elizabeth; Chen, Wei-Ti; Brion, John; Eller, Lucille; Kirksey, Kenn; Wantland, Dean; Portillo, Carmen; Corless, Inge B.; Voss, Joachim; Iipinge, Scholastika; Spellmann, Mark; Holzemer, William L.



Spatial structure increases the waiting time for cancer  

NASA Astrophysics Data System (ADS)

Cancer results from a sequence of genetic and epigenetic changes that lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells and thus to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been attracting increasing interest in recent years. A great deal of effort has been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones and decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help us to predict the onset of cancers with pronounced spatial structure and to interpret spatially sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer and possibly other cancers where spatial structure matters.

Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar



Increased commuting to school time reduces sleep duration in adolescents.  


Active travel to school has been referred to as one way of increasing the level of daily physical exercise, but the actual impacts on student's general health are not clear. Recently, a possible association between active travel to school and the duration of sleep was suggested. Thus, the aim was of this study to investigate the associations between the type of transportation and travel time to school, the time in bed and sleepiness in the classroom of high school students. Information on sleeping habits and travel to school of 1126 high school students were analyzed, where 55.1% were girls with an average age of 16.24 (1.39) years old, in Santa Maria Municipality, Rio Grande do Sul, Brazil. Multiple linear regression and adjusted prevalence rates analyses were carried out. The frequency of active travel found was 61.8%. Associations between time in bed, sleepiness in the classroom and the type of transportation (active or passive) were not identified. Nevertheless, the time in bed was inversely associated with the travel time (p?=?0.036) and with a phase delay. In the adjusted analysis, active travel was more incident for the students of schools in the suburbs (PR: 1.68; CI: 1.40-2.01) in comparison with the students of schools in the center. Therefore, longer trips were associated with a reduction of sleep duration of morning and night groups. Interventions concerning active travel to school must be carried out cautiously in order not to cause a reduction of the sleeping time. PMID:24152062

Pereira, Erico Felden; Moreno, Claudia; Louzada, Fernando Mazzilli



Increasing reach of quitline services in a US state with comprehensive tobacco treatment  

PubMed Central

Objective The population reach of tobacco quitlines is an important measure of treatment seeking and penetration of services. Maine offers an opportunity to examine temporal changes in quitline reach and referral sources in the context of a comprehensive tobacco treatment programme. The impact of a $1.00 cigarette tax increase is also examined. Methods This is a descriptive analysis of Maine Tobacco Helpline call volume September 2001 to December 2006. Annual reach was estimated using a cross sectional state surveillance survey. Weekly call volume was examined during 2005, a year of marked changes in tobacco taxes and quitline resources. Referral patterns were analysed yearly. Results Maine's Tobacco Helpline observed more than a threefold increase in population reach during a four year interval, from 1.9% to over 6% per year. Calls increased substantially in 2005, concurrent with added hours of operation and a rise in the cigarette tax. Over time, callers increasingly reported hearing about the quitline from health professionals, from 10% in 2001 to 38% in 2006. Conclusions Tobacco treatment programmes offering free nicotine therapy and professional medical education can drive quitline utilisation over time. Call volume can also be affected by quitline operational and policy changes that promote the reduction of tobacco use. PMID:18048629

Woods, Susan Swartz; Haskins, Amy E



Real Time Search User Behavior Real time search is an increasingly important area of  

E-print Network

. The most frequently used terms accounted for only 0.03% of the total terms. Concerning search topics Web search. Searchers of real time content often repeat queries overtime, perhaps indicating long term content increasingly enters the main stream. Keywords Real time search, real time content, Collecta

Jansen, James


Acetate treatment increases fatty acid content in LPS-stimulated BV2 microglia.  


Acetate supplementation increases plasma acetate, brain acetyl-CoA, histone acetylation, phosphocreatine levels, and is anti-inflammatory in models of neuroinflammation and neuroborreliosis. Although radiolabeled acetate is incorporated into the cellular lipid pools, the effect that acetate supplementation has on lipid deposition has not been quantified. To determine the impact acetate-treatment has on cellular lipid content, we investigated the effect of acetate in the presence of bacterial lipopolysaccharide (LPS) on fatty acid, phospholipid, and cholesterol content in BV2 microglia. We found that 1, 5, and 10 mM of acetate in the presence of LPS increased the total fatty acid content in BV2 cells by 23, 34, and 14 % at 2 h, respectively. Significant increases in individual fatty acids were also observed with all acetate concentrations tested with the greatest increases occurring with 5 mM acetate in the presence of LPS. Treatment with 5 mM acetate in the absence of LPS increased total cholesterol levels by 11 %. However, neither treatment in the absence of LPS significantly altered the content of individual phospholipids or total phospholipid content. To determine the minimum effective concentration of acetate we measured the time- and concentration-dependent changes in histone acetylation using western blot analysis. These studies showed that 5 mM acetate was necessary to induce histone acetylation and at 10 mM acetate, the histone acetylation-state increased as early as 0.5 h following the start of treatment. These data suggest that acetate increases fatty acid content in LPS-stimulated BV2 microglia that is reflected by an increase in fatty acids esterified into membrane phospholipids. PMID:24852320

Bhatt, Dhaval P; Rosenberger, Thad A



Early postnatal dexamethasone treatment and increased incidence of cerebral palsy  

Microsoft Academic Search

OBJECTIVETo study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease.METHODSThe original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who

E S Shinwell; M Karplus; D Reich; Z Weintraub; S Blazer; D Bader; S Yurman; T Dolfin; A Kogan; S Dollberg; E Arbel; M Goldberg; I Gur; N Naor; L Sirota; S Mogilner; A Zaritsky; M Barak; E Gottfried



Timely diagnosis and treatment essential in glomerulonephritis.  


Glomerulonephritis is an important cause of kidney disease and, in the UK, the most common diagnosis in patients receiving chronic dialysis or waiting for kidney transplantation. A key feature is the presence of urinary abnormalities (proteinuria ± haematuria). Patients with nephrotic syndrome typically present with peripheral oedema, massive urinary protein loss and associated low serum albumin levels. Blood pressure and renal function, as measured by eGFR, are usually normal initially. Patients presenting with nephritic syndrome tend to be hypertensive with dipstick-positive or visible haematuria. There may be rapidly progressive renal dysfunction and fall in eGFR. Many patients will have a background genetic susceptibility to glomerulonephritis which may be triggered by environmental, infective or autoimmune factors. Autoimmunity, in combination with genetic factors, is responsible for a significant proportion of cases of glomerulonephritis. Infective agents such as viruses can precipitate minimal change disease. NSAIDs, lithium, penicillamine and heroin can cause nephrotic syndrome. Timely diagnosis and treatment of glomerulonephritis can help to minimise both the occurrence and severity of complications. All patients with glomerulonephritis should be managed according to CKD guidelines with CKD stage-appropriate measurement of renal function, blood pressure, and proteinuria. PMID:25816500

Lewis, Gareth; Maxwell, Alexander P



ANOXIA, Treatment by Oxygen Deprivation, Optimizing Treatment Time of Museum Objects  

E-print Network

ANOXIA, treatment by oxygen deprivation is largely used for decontamination and disinfestation of cellulose and protein-based organic materials. More specifically this method is applied to more than one hundred thousand of objects destinated for a new museum in Paris, "Musee du Quai Branly". We describe the anoxia installation in this museum and report the result of a study regarding the efficiency of this method and the optimum treatment time, crucial for treating a large collection. We show that the standard 21 days of exposure is not always the optimal choice. Temperature plays a crucial role for hastening the death of insects found within objects. At a temperature of 25C, it is entirely possible to reduce exposure times to 10 or 15 days for the insect species commonly found in museums. The oxygen drop times is between 1 and 2 days for most objects, depending on type and porosity of materials. This corresponds to a treatment time between 15 and 16 days. The effect of humidity is less clear. It can increase the necessary treatment time both for larvae and for adult insects.

Michele Gunn; Houri Ziaeepour; Fabrice Merizzi; Christitiane Naffah



Smoking increases the risk of relapse after successful tuberculosis treatment  

PubMed Central

Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729

d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha



Timing of Curative Treatment for Prostate Cancer: A Systematic Review  

PubMed Central

Context Delaying definitive therapy unfavourably affects outcomes in many malignancies. Diagnostic, psychological, and logistical reasons but also active surveillance (AS) strategies can lead to treatment delay, an increase in the interval between the diagnosis and treatment of prostate cancer (PCa). Objective To review and summarise the current literature on the impact of treatment delay on PCa oncologic outcomes. Evidence acquisition A comprehensive search of PubMed and Embase databases until 30 September 2012 was performed. Studies comparing pathologic, biochemical recurrence (BCR), and mortality outcomes between patients receiving direct and delayed curative treatment were included. Studies presenting single-arm results following AS were excluded. Evidence synthesis Seventeen studies were included: 13 on radical prostatectomy, 3 on radiation therapy, and 1 combined both. A total of 34 517 PCa patients receiving radical local therapy between 1981 and 2009 were described. Some studies included low-risk PCa only; others included a wider spectrum of disease. Four studies found a significant effect of treatment delay on outcomes in multivariate analysis. Two included low-risk patients only, but it was unknown whether AS was applied or repeat biopsy triggered active therapy during AS. The two other studies found a negative effect on BCR rates of 2.5–9 mo delay in higher risk patients (respectively defined as any with T ?2b, prostate-specific antigen >10, Gleason score >6, >34–50% positive cores; or D’Amico intermediate risk-group). All studies were retrospective and nonrandomised. Reasons for delay were not always clear, and time-to-event analyses may be subject to bias. Conclusions Treatment delay of several months or even years does not appear to affect outcomes of men with low-risk PCa. Limited data suggest treatment delay may have an impact on men with non–low-risk PCa. Most AS protocols suggest a confirmatory biopsy to avoid delaying treatment in those who harbour higher risk disease that was initially misclassified. PMID:23453419

van den Bergh, Roderick C.N.; Albertse, Peter C.; Bangma, Chris H.; Freedlan, Stephen J.; Graefen, Markus; Vickers, Andrew; van der Poel, Henk G.



A Role for Cognitive Rehabilitation in Increasing the Effectiveness of Treatment for Alcohol Use Disorders  

PubMed Central

Neurocognitive impairments are prevalent in persons seeking treatment for alcohol use disorders (AUDs). These impairments and their physical, social, psychological and occupational consequences vary in severity across persons, much like those resulting from traumatic brain injury; however, due to their slower course of onset, alcohol-related cognitive impairments are often overlooked both within and outside of the treatment setting. Evidence suggests that cognitive impairments can impede treatment goals through their effects on treatment processes. Although some recovery of alcohol-related cognitive impairments often occurs after cessation of drinking (time-dependent recovery), the rate and extent of recovery is variable across cognitive domains and individuals. Following a long hiatus in scientific interest, a new generation of research aims to facilitate treatment process and improve AUD treatment outcomes by directly promoting cognitive recovery (experience-dependent recovery). This review updates knowledge about the nature and course of cognitive and brain impairments associated with AUD, including cognitive effects of adolescent AUD. We summarize current evidence for indirect and moderating relationships of cognitive impairment to treatment outcome, and discuss how advances in conceptual frameworks of brain-behavior relationships are fueling the development of novel AUD interventions that include techniques for cognitive remediation. Emerging evidence suggests that such interventions can be effective in promoting cognitive recovery in persons with AUD and other substance use disorders, and potentially increasing the efficacy of AUD treatments. Finally, translational approaches based on cognitive science, neurophysiology, and neuroscience research are considered as promising future directions for effective treatment development that includes cognitive rehabilitation. PMID:23412885

Bates, Marsha E.; Buckman, Jennifer F.; Nguyen, Tam T.



Reducing time limits: a means to increase behavior of retardates.  


A common assumption in special education is that temporal limits for a task should be expanded so that ample time is provided for completing the work. This study describes the opposite strategy of restricting temporal limits to augment academic performance. Three educable retarded children received token reinforcement contingent on the number of correct math problems answered during daily sessions. A reversal design was used to assess the effects of an abrupt reduction in time limits (20-5-20 min) and a graduated sequence of reductions (20-15-10-5-20 min). The graduated sequence resulted in rate increases of correct responding ranging from 125% to 266% and these gains endured when temporal limits were again expanded. In contrast, the abrupt shift produced interfering emotional behaviors and rate decreases in academic performance of 25% to 80%. The findings indicate that systematically restricting temporal limits for an academic task can further enhance the performance of slow learners already maintained by a token system. PMID:977515

Ayllon, T; Garber, S; Pisor, K



Reducing video frame rate increases remote optimal focus time  

NASA Technical Reports Server (NTRS)

Twelve observers made best optical focus adjustments to a microscope whose high-resolution pattern was video monitored and displayed first on a National Television System Committee (NTSC) analog color monitor and second on a digitally compressed computer monitor screen at frame rates ranging (in six steps) from 1.5 to 30 frames per second (fps). This was done to determine whether reducing the frame rate affects the image focus. Reducing frame rate has been shown to be an effective and acceptable means of reducing transmission bandwidth of dynamic video imagery sent from Space Station Freedom (SSF) to ground scientists. Three responses were recorded per trial: time to complete the focus adjustment, number of changes of focus direction, and subjective rating of final image quality. It was found that: the average time to complete the focus setting increases from 4.5 sec at 30 fps to 7.9 sec at 1.5 fps (statistical probability = 1.2 x 10(exp -7)); there is no significant difference in the number of changes in the direction of focus adjustment across these frame rates; and there is no significant change in subjectively determined final image quality across these frame rates. These data can be used to help pre-plan future remote optical-focus operations on SSF.

Haines, Richard F.



Treatments to Increase Social Awareness and Social Skills  

Microsoft Academic Search

\\u000a There is an extensive literature on methods for increasing the social awareness and social skills of people with autism spectrum\\u000a disorders (ASDs) of every diagnostic category and every age. This work varies in research quality from the mediocre to the\\u000a exemplary, although the exemplary are outnumbered by the less rigorous. One reason for the focus on treating social behaviors\\u000a is

Suzannah J. Ferraioli; Sandra L. Harris


Surimi wash water treatment for protein recovery: effect of chitosan–alginate complex concentration and treatment time on protein adsorption  

Microsoft Academic Search

Chitosan (Chi), a protein recovery agent for the treatment of aqueous food processing streams, appears to work by mechanical entrapment and electrostatic interaction of chitosan amino groups with anionic groups on proteins. Chitosan effectiveness for recovering soluble proteins from surimi wash water (SWW) is increased by complexation with alginate (Alg) and by adjusting complex concentration and treatment time. Flocculation at

Singgih Wibowo; Gonzalo Velazquez; Vivek Savant; J. Antonio Torres



Real-time fault detection and isolation in biological wastewater treatment plants  

E-print Network

Real-time fault detection and isolation in biological wastewater treatment plants F. Baggiani and S aspect in the domain of advanced control of Waste Water Treatment Plants (WWTP) (Olsson & Newell Automatic fault detection is becoming increasingly important in wastewater treatment plant operation, given


Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.  


Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life. PMID:24945924

Ko, Meng-Chang; Hung, Yu-Hui; Ho, Pei-Yin; Yang, Yi-Ling; Lu, Kwok-Tung




SciTech Connect

Gelled polymer treatments are applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report describes the results of a three-year research program aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production. The work focused on the gel system composed of polyacrylamide and chromium acetate. The molar mass of the polymer was about six million. Chromium(III) acetate reacted and formed crosslinks between polymer molecules. The crosslinked polymer molecules, or pre-gel aggregates, combine and grow to eventually form a 3-dimensional gel. A fundamental study to characterize the formation and growth of pre-gel aggregates was conducted. Two methods, flow field-flow fractionation (FFFF) and multi-angle laser light scattering (MALLS) were used. Studies using FFFF were inconclusive. Data taken using MALLS showed that at the gel time the average molar mass of gel aggregates increased by a factor of about three while the average size increase was approximately 50%. Increased acetate concentration in the gelant increases the gel time. The in situ performance of an added-acetate system was investigated to determine the applicability for in-depth treatments. Increased acetate concentrations delayed the development of increased flow resistance during gelant injection in short sandpacks. The development of increased flow resistance (in situ gelation) was extended from 2 to 34 days by increasing the acetate-to-chromium ratio from 38 to 153. In situ gelation occurred at a time that was approximately 22% of the bulk gelation time. When carbonate rocks are treated with gel, chromium retention in the rock may limit in-depth treatment. Chromium retention due to precipitation was investigated by flowing chromium acetate solutions through carbonate rock. Chromium precipitated faster in the rocks than in beaker experiments at similar conditions. A mathematical model previously developed fit the precipitation data reasonably well. The stability of gels when subjected to stress was investigated by experiments with gels placed in tubes and in laboratory-scale fractures. Rupture pressures for gels placed in small diameter tubes were correlated with the ratio of tube length to tube ID. In fractures, fluid leakoff from the fracture to adjacent matrix rock affected gel formation and gel stability in a positive way. Disproportionate permeability reduction (DPR) was studied in unconsolidated sandpacks and in Berea sandstone cores. A conceptual model was developed to explain the presence of DPR. The effect of a pressure gradient, imposed by injection of oil or brine, on the permeability of gel-treated cores was investigated. DPR increased significantly as the pressure gradient was decreased. The magnitude of the pressure gradient had a much larger effect on water permeability than on oil permeability.

G.P. Willhite; D.W. Green; C.S. McCool



Time is up: increasing shadow price of time in primary-care office visits.  


A physician's own time is a scarce resource in primary care, and the physician must constantly evaluate the gain from spending more time with the current patient against moving to address the health-care needs of the next. We formulate and test two alternative hypotheses. The first hypothesis is based on the premise that with time so scarce, physicians equalize the marginal value of time across patients. The second, alternative hypothesis states that physicians allocate the same time to each patient, regardless of how much the patient benefits from the time at the margin. For our empirical work, we examine the presence of a sharply increasing subjective shadow price of time around the 'target' time using video recordings of 385 visits by elderly patients to their primary care physician. We structure the data at the 'topic' level and find evidence consistent with the alternative hypothesis. Specifically, time elapsed within a visit is a very strong determinant of the current topic being the 'last topic'. This finding implies the physician's shadow price of time is rising during the course of a visit. We consider whether dislodging a target-time mentality from physicians (and patients) might contribute to more productive primary care practice. PMID:21442688

Tai-Seale, Ming; McGuire, Thomas



Does Integrated Trauma-Informed Substance Abuse Treatment Increase Treatment Retention?  

ERIC Educational Resources Information Center

This article presents findings from a quasi-experimental, nonrandomized group design study that explored whether trauma-enhanced substance abuse treatment results in longer residential treatment stays and improved outcomes compared with treatment-as-usual. We used a subsample (N = 461) of participants in the Women, Co-Occurring Disorders and…

Amaro, Hortensia; Chernoff, Miriam; Brown, Vivian; Arevalo, Sandra; Gatz, Margaret



Evaluation of medical treatments to increase survival of ebullism in guinea pigs  

NASA Technical Reports Server (NTRS)

Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.



Surface Treatments to Increase the Perceived Vibration of a Piezoelectric foil Tuyet-Trinh T. Phan  

E-print Network

Surface Treatments to Increase the Perceived Vibration of a Piezoelectric foil by Tuyet-Trinh T Professor of Mechanical Engineering Chairman of the Undergraduate Thesis Committee #12;2 Surface Treatments by 10-12 dB. All the successful surface treatments incorporated a stiff mylar lamination that converted

Srinivasan, Mandayam A.


Potential Increase in Fruit Fly (Diptera: Tephritidae) Interceptions Using Ionizing Irradiation Phytosanitary Treatments  

Technology Transfer Automated Retrieval System (TEKTRAN)

Ionizing irradiation is a postharvest phytosanitary treatment that is used increasingly in the world and shows further promise with some advantages compared to other treatments. Its chief disadvantage is that, unlike all other commercially used treatments, it does not provide acute mortality but pr...


Increase in Indoleacetic Acid Oxidase Activity of Winter Wheat by Cold Treatment and Gibberellic Acid 1  

PubMed Central

The activity of indoleacetic acid oxidase increased 10-fold during 40 days of cold treatment of winter wheat seedlings. Puromycin and 6-methyl purine inhibited indoleacetic acid oxidase development in the cold. Addition of gibberellic acid stimulated indoleacetic acid oxidase development during germination at room temperature and during cold treatment. Amo-1618 inhibited indoleacetic acid oxidase development before and during cold treatment. Indoleacetic acid treatment increased indoleacetic acid oxidase activity during germination at room temperature while no significant effect on activity was observed during cold treatment. PMID:16657327

Bolduc, Reginald J.; Cherry, Joe H.; Blair, Byron O.



Influence of electrolytic treatment time on the corrosion resistance of Ni-Ti orthodontic wire.  


The purpose of this study was to examine the use of electrolytic treatment, which can improve the corrosion resistance of Ni-Ti orthodontic wires, to minimize adverse effects. Electrolytic treatment of Ni-Ti wires was performed in a solution composed of glycerol and lactic acid for 5, 15, or 30 min. The anodic polarization test, three-point bending test, and X-ray photoelectron spectroscopic analysis of the wire surface were performed to explore an optimal treatment condition. Breakdown potentials of treated wires increased with increasing treatment time and higher corrosion resistance was obtained by performing the electrolytic treatment for more than 5 min. The relative concentration of nickel in the layer was decreased in inverse proportion to the treatment time. The results suggest that the commercial Ni-Ti wire with low corrosion resistance can be improved by the electrolytic treatment for more than 5 min. PMID:23538767

Kaneto, Maki; Namura, Yasuhiro; Tamura, Takahiko; Shimizu, Noriyoshi; Tsutsumi, Yusuke; Hanawa, Takao; Yoneyama, Takayuki



Olanzapine, but Not Fluoxetine, Treatment Increases Survival in Activity-Based Anorexia in Mice  

PubMed Central

Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates. The activity-based anorexia (ABA) phenomenon models aspects of AN in rodents, including progressive weight loss, reduced food intake, and hyperactivity. First, we optimized the ABA paradigm for mice. We compared mouse strains (Balb/cJ, A/J) for susceptibility with ABA, and evaluated the effects of different food access durations (2, 4, 6, 8, and 10?h) on ABA parameters. Balb/cJ mice exhibited significantly shorter survival time (days until 25% bodyweight loss) in the ABA paradigm compared with A/J mice. Furthermore, 6?h of food access reduced survival in mice housed with wheels without reducing survival in mice housed without wheels. We then evaluated the effects of chronic treatment with fluoxetine (4 weeks) or subchronic treatment with olanzapine (OLZ) (1 week) on ABA in BALB/cJ mice. OLZ (12?mg/kg/day) significantly increased survival and reduced food anticipatory activity (FAA). However, OLZ did not alter food intake or running wheel activity during ad-lib feeding (baseline) or restriction conditions, or in mice housed without wheels. Fluoxetine (18?mg/kg/day) increased food intake and reduced FAA, but did not alter survival. Here, we report for the first time that OLZ, but not fluoxetine, reduces ABA in mice. Our findings indicate further need for clinical investigations into the effects of OLZ, but not selective serotonin reuptake inhibitors, on core features of AN. PMID:22395732

Klenotich, Stephanie J; Seiglie, Mariel P; McMurray, Matthew S; Roitman, Jamie D; Le Grange, Daniel; Dugad, Priya; Dulawa, Stephanie C



Response Time Analysis in Cognitive Tasks with Increasing Difficulty  

ERIC Educational Resources Information Center

In the present study, speeded tasks with differing assumed difficulties of the trials are regarded as a special class of simple cognitive tasks. Exploratory latent growth modeling with data-driven shape of a growth curve and nonlinear structured latent curve modeling with predetermined monotonically increasing functions were used to analyze…

Dodonov, Yury S.; Dodonova, Yulia A.



On-Line Scheduling Policies for a Class of IRIS (Increasing Reward with Increasing Service) Real-Time Tasks  

Microsoft Academic Search

We consider a real time task model where a task receives a “reward” that depends on the amount of service received prior to its deadline. The reward of the task is assumed to be an increasing function of the amount of service that it receives, i.e., the task has the property that it receives increasing reward with increasing service (IRIS).

Jayanta K. Dey; James F. Kurose; Donald F. Towsley



Increasing LARC utilization: any woman, any place, any time.  


Intrauterine contraceptive devices and the progestin implant are the most effective long-acting reversible contraception (LARC) methods available for preventing unintended pregnancy. LARC devices are safe, non-user-dependent methods that have the highest rates of continuation and satisfaction of all reversible contraceptives. Use of these contraceptives remains low in the United States due to several barriers including: misperceptions among both providers and patients; cost barriers; and patient access to the devices. Increasing the opportunities for women to access LARC methods in the primary care, postabortion, and postpartum setting can be achieved by addressing the system, provider, and patient barriers that exist. PMID:25314089

Hathaway, Mark; Torres, Leah; Vollett-Krech, Jennifer; Wohltjen, Hannah



Increases in Levels of Collagen Types I and IV Messenger Ribonucleic Acid in Murine Kidneys after Treatment with Ciclosporin  

Microsoft Academic Search

We investigated changes in the levels of mRNA transcripts encoding types I and IV collagen in the kidney following the administration of ciclosporin (CS) in mice. Daily doses of CS increased the levels of mRNAs encoding collagen types I and IV in whole kidneys harvested 4 weeks after treatment. At this time point, neither a reduction of renal function detected

Gunter Wolf; Eric G. Neilson



Warming rather than increased precipitation increases soil recalcitrant organic carbon in a semiarid grassland after 6 years of treatments.  


Improved understanding of changes in soil recalcitrant organic carbon (C) in response to global warming is critical for predicting changes in soil organic C (SOC) storage. Here, we took advantage of a long-term field experiment with increased temperature and precipitation to investigate the effects of warming, increased precipitation and their interactions on SOC fraction in a semiarid Inner Mongolian grassland of northern China since April 2005. We quantified labile SOC, recalcitrant SOC and stable SOC at 0-10 and 10-20 cm depths. Results showed that neither warming nor increased precipitation affected total SOC and stable SOC at either depth. Increased precipitation significantly increased labile SOC at the 0-10 cm depth. Warming decreased labile SOC (P?=?0.038) and marginally but significantly increased recalcitrant SOC at the 10-20 cm depth (P?=?0.082). In addition, there were significant interactive effects of warming and increased precipitation on labile SOC and recalcitrant SOC at the 0-10 cm depth (both P<0.05), indicating that that results from single factor experiments should be treated with caution because of multi-factor interactions. Given that the absolute increase of SOC in the recalcitrant SOC pool was much greater than the decrease in labile SOC, and that the mean residence time of recalcitrant SOC is much greater, our results suggest that soil C storage at 10-20 cm depth may increase with increasing temperature in this semiarid grassland. PMID:23341995

Zhou, Xiaoqi; Chen, Chengrong; Wang, Yanfen; Smaill, Simeon; Clinton, Peter



Warming Rather Than Increased Precipitation Increases Soil Recalcitrant Organic Carbon in a Semiarid Grassland after 6 Years of Treatments  

PubMed Central

Improved understanding of changes in soil recalcitrant organic carbon (C) in response to global warming is critical for predicting changes in soil organic C (SOC) storage. Here, we took advantage of a long-term field experiment with increased temperature and precipitation to investigate the effects of warming, increased precipitation and their interactions on SOC fraction in a semiarid Inner Mongolian grassland of northern China since April 2005. We quantified labile SOC, recalcitrant SOC and stable SOC at 0–10 and 10–20 cm depths. Results showed that neither warming nor increased precipitation affected total SOC and stable SOC at either depth. Increased precipitation significantly increased labile SOC at the 0–10 cm depth. Warming decreased labile SOC (P?=?0.038) and marginally but significantly increased recalcitrant SOC at the 10–20 cm depth (P?=?0.082). In addition, there were significant interactive effects of warming and increased precipitation on labile SOC and recalcitrant SOC at the 0–10 cm depth (both P<0.05), indicating that that results from single factor experiments should be treated with caution because of multi-factor interactions. Given that the absolute increase of SOC in the recalcitrant SOC pool was much greater than the decrease in labile SOC, and that the mean residence time of recalcitrant SOC is much greater, our results suggest that soil C storage at 10–20 cm depth may increase with increasing temperature in this semiarid grassland. PMID:23341995

Zhou, Xiaoqi; Chen, Chengrong; Wang, Yanfen; Smaill, Simeon; Clinton, Peter



Increasing substance abuse treatment compliance for persons with traumatic brain injury.  


This study compared 3 methods of increasing participation in substance abuse treatment for clients with traumatic brain injury. Participants (N = 195) were randomly assigned to 4 conditions: (a) motivational interview, (b) reduction of logistical barriers to attendance, (c) financial incentive, and (d) attention control. Four interviewers conducted structured, brief telephone interventions targeting the timeliness of signing an individualized service plan. Participants assigned to the barrier reduction (74%) and financial incentive (83%) groups were more likely to sign within 30 days compared with the motivational interview (45%) and attention control (45%) groups. Similar results were observed for time to signing, perfect attendance at appointments, and premature termination during the following 6 months. Extent of psychiatric symptoms was the only significant covariate. PMID:16011383

Corrigan, John D; Bogner, Jennifer; Lamb-Hart, Gary; Heinemann, Allen W; Moore, Dennis



Increasing preoperative dislocations and total time of dislocation affect surgical management of anterior shoulder instability  

PubMed Central

Purpose: Our purpose was to determine the relationship between number of preoperative shoulder dislocations and total dislocation time and the need to perform bone deficiency procedures at the time of primary anterior instability surgery. Our hypothesis was that need for bone deficiency procedures would increase with the total number and hours of dislocation. Materials and Methods: A retrospective review was performed of primary instability surgeries performed by a single surgeon. Patients with <25% glenoid bone loss were treated with an isolated arthroscopic Bankart repair. Those who also had an engaging Hill-Sachs lesion underwent arthroscopic Bankart repair with remplissage. Patients with >25% glenoid bone loss were treated with Latarjet reconstruction. Number of dislocations and total dislocation time were examined for their relationship with the treatment method. Results: Ten arthroscopic Bankart repairs, 13 arthroscopic Bankart plus remplissage procedures, and 9 Latarjet reconstructions were available for review. Total dislocations (P = 0.012) and total hours of dislocation (P = 0.019) increased from the Bankart, to the remplissage, to the Latarjet groups. Patients with a total dislocation time of 5 h or more were more likely to require a Latarjet reconstruction (P = 0.039). Patients with only 1 preoperative dislocation were treated with an isolated Bankart repair in 64% (7 of 11) of cases, whereas those with 2 or more dislocations required a bone loss procedure in 86% (18 of 21) of cases (P = 0.013). Conclusion: Increasing number of dislocations and total dislocation time are associated with the development of glenoid and humeral head bony lesions that alter surgical management of anterior shoulder instability. The necessity for the addition of a remplissage to an arthroscopic Bankart repair or the use of a Latarjet reconstruction increases with only 1 recurrent dislocation. Level of evidence: Level III, retrospective comparative study. PMID:25709237

Denard, Patrick J.; Dai, Xuesong; Burkhart, Stephen S.



Pancreatic cancer Increased organ sparing using shape-based treatment plan optimization for  

E-print Network

Pancreatic cancer Increased organ sparing using shape-based treatment plan optimization Available online 15 June 2011 Keywords: Pancreatic cancer Intensity modulated radiotherapy (IMRT) Treatment with pancreatic cancer was queried to find patients with less favorable PTV-OAR configuration than a new case

Kazhdan, Michael


Treating stuttering in young children: predicting treatment time in the Lidcombe Program.  


It is known that children may recover from stuttering without formal treatment during the first years after onset. Consequently, the timing of professional, early stuttering intervention is a pressing issue in speech-language pathology. This report presents data pertinent to this issue for 261 preschool-age children who received the Lidcombe Program of early stuttering intervention. Of these children, 250 completed the program and were considered by their clinicians to have been treated successfully. For the children who were treated successfully, logistical regression analyses were used to determine whether age, gender, period from onset to treatment, and stuttering severity related systematically to the time required for treatment. The present data confirmed previous reports that a median of 11 clinic visits was required to achieve zero or near-zero stuttering with the Lidcombe Program. Results were also consistent with a preliminary report of 14 children (C. W. Starkweather & S. R. Gottwald, 1993) showing a significant relation between stuttering severity and the time needed for treatment, with children with more severe stuttering requiring longer treatment times than children with less severe stuttering. However, results did not associate either increasing age or increased onset-to-treatment intervals with longer treatment times. This finding is not consistent with the Starkweather and Gottwald report, which linked advancing age with longer treatment time. In fact, the present data suggest that, for a short period after stuttering onset in the preschool years, a short delay in treatment does not appear to increase treatment time. An important caveat to these data is that they cannot be generalized to late childhood or early adolescence. The present findings are discussed in relation to natural recovery from stuttering. PMID:11193964

Jones, M; Onslow, M; Harrison, E; Packman, A



On Optimal Treatment Regimes Selection for Mean Survival Time  

PubMed Central

In clinical studies with time-to-event as a primary endpoint, one main interest is to find the best treatment strategy to maximize patients’ mean survival time. Due to patient’s heterogeneity in response to treatments, great efforts have been devoted to developing optimal treatment regimes by integrating individuals’ clinical and genetic information. A main challenge arises in the selection of important variables that can help to build reliable and interpretable optimal treatment regimes since the dimension of predictors may be high. In this paper, we propose a robust loss-based estimation framework that can be easily coupled with shrinkage penalties for both estimation of optimal treatment regimes and variable selection. The asymptotic properties of the proposed estimators are studied. Moreover, a model-free estimator of restricted mean survival time under the derived optimal treatment regime is developed and its asymptotic property is studied. Simulations are conducted to assess the empirical performance of the proposed method for parameter estimation, variable selection, and optimal treatment decision. An application to an AIDS clinical trial data set is given to illustrate the method. PMID:25515005

Geng, Yuan; Zhang, Hao Helen; Lu, Wenbin



On optimal treatment regimes selection for mean survival time.  


In clinical studies with time-to-event as a primary endpoint, one main interest is to find the best treatment strategy to maximize patients' mean survival time. Due to patient's heterogeneity in response to treatments, great efforts have been devoted to developing optimal treatment regimes by integrating individuals' clinical and genetic information. A main challenge arises in the selection of important variables that can help to build reliable and interpretable optimal treatment regimes as the dimension of predictors may be high. In this paper, we propose a robust loss-based estimation framework that can be easily coupled with shrinkage penalties for both estimation of optimal treatment regimes and variable selection. The asymptotic properties of the proposed estimators are studied. Moreover, a model-free estimator of restricted mean survival time under the derived optimal treatment regime is developed, and its asymptotic property is studied. Simulations are conducted to assess the empirical performance of the proposed method for parameter estimation, variable selection, and optimal treatment decision. An application to an AIDS clinical trial data set is given to illustrate the method. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25515005

Geng, Yuan; Zhang, Hao Helen; Lu, Wenbin



Neoadjuvant-intensified treatment for rectal cancer: Time to change?  

PubMed Central

AIM: To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer. METHODS: Between January 2007 and December 2011, 80 patients with histologically confirmed rectal adenocarcinoma were enrolled. Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes. Patients received intensified combined modality treatment, consisting of neoadjuvant radiation therapy (50.4-54.0 Gy) and infusional chemotherapy (oxaliplatin 50 mg/m2) on the first day of each week, plus five daily continuous infusions of fluorouracil (200 mg/m2 per die) from the first day of radiation therapy until radiotherapy completion. Patients received five or six cycles of oxaliplatin based on performance status, clinical lymph node involvement, and potential risk of a non-sphincter-conserving surgical procedure. Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment; adjuvant chemotherapy treatment was left to the oncologist’s discretion and was recommended in patients with positive lymph nodes. After treatment, all patients were monitored every three months for the first year and every six months for the subsequent years. RESULTS: Of the 80 patients enrolled, 75 patients completed the programmed neoadjuvant radiochemotherapy treatment. All patients received the radiotherapy prescribed total dose; five patients suspended chemotherapy indefinitely because of chemotherapy-related toxicity. At least five cycles of oxaliplatin were administered to 73 patients. Treatment was well tolerated with high compliance and a good level of toxicity. Most of the acute toxic effects observed were classified as grades 1-2. Proctitis grade 2 was the most common symptom (63.75%) and the earliest manifestation of acute toxicity. Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients (3.75%). Seventy-seven patients underwent surgery; low anterior resection was performed in 52 patients, Miles’ surgery in 11 patients and total mesorectal excision in nine patients. Fifty patients showed tumor downsizing ? 50% pathological downstaging in 88.00% of tumors. Out of 75 patients surviving surgery, 67 patients (89.33%) had some form of downstaging after preoperative treatment. A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response (stage ypT1ypN0) in six patients. An involvement of the radial margin was never present. During surgery, intra-abdominal metastases were found in only one patient (1.25%). Initially, 45 patients required an abdominoperineal resection due to a tumor distal margin ? 5 cm from the anal verge. Of these patients, only seven of them underwent Miles’ surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup. Fourteen patients received postoperative chemotherapy. In the full analysis of enrolled cohort, eight of the 80 patients died, with seven deaths related to rectal cancer and one to unrelated causes. Local recurrences were observed in seven patients (8.75%) and distant metastases in 17 cases (21.25%). The five-year rate of overall survival rate was 90.91%. Using a median follow-up time of 28.5 mo, the cumulative incidence of local recurrences was 8.75%, and the overall survival and disease-free survival rates were 90.00% and 70.00%, respectively. CONCLUSION: The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival, likely due to an increase in local tumor control. PMID:23716984

Musio, Daniela; De Felice, Francesca; Bulzonetti, Nadia; Guarnaccia, Roberta; Caiazzo, Rossella; Bangrazi, Caterina; Raffetto, Nicola; Tombolini, Vincenzo



L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice  

E-print Network

and the associated insu- lin resistance and changes in serum levels of adiponectin, suggesting that increases in ROS.001). L-4F treatment increased serum adiponectin levels (P , 0.037) and de- creased adipogenesis in mouse oxidation, liver insulin action, and glucose uptake and positively affect serum triglyceride levels (12

Abraham, Nader G.


Amphetamine Treatment Increases Corticotropin-Releasing Factor Receptors in the Dorsal Raphe Nucleus  

PubMed Central

Psychostimulant use increases anxious behavior, likely through interactions between central corticotropin-releasing factor (CRF) and serotonergic systems. The current study examined whether chronic amphetamine treatment (2.5 mg/kg, 14 days) or withdrawal altered CRF receptor densities in the serotonergic dorsal raphe nucleus (dRN). Amphetamine treatment increased CRF2 receptor densities in most subregions of the dRN, and CRF2 receptors were still elevated following 6 weeks of withdrawal. No changes in CRF1 receptor densities were observed following amphetamine treatment or during withdrawal. Selective increases in dRN CRF2 receptors may be related to increased anxiety-like behaviors following psychostimulant use. PMID:18585412

Pringle, Ronald B.; Mouw, Nicholas J.; Lukkes, Jodi L.; Forster, Gina L.



NIH study finds increases in risk of certain leukemias related to treatment

A new study describes the pattern of risk for chemotherapy-related acute myeloid leukemia among adult cancer survivors over the past three decades who have previously been treated with chemotherapy for other cancers. These patterns coincide with major shifts in treatment practices. In particular, the study found that the risk of treatment-related AML among patients treated for non-Hodgkin lymphoma has increased steadily during the last few decades.


Subchronic milnacipran treatment increases basal extracellular noradrenaline concentrations in the medial prefrontal cortex of rats.  


In this study, we investigated the acute effects of milnacipran, a serotonin-noradrenaline reuptake inhibitor, following subchronic treatment with milnacipran (30 mg/kg periorally for 7 days) on extracellular noradrenaline, dopamine and serotonin concentrations in the medial prefrontal cortex. Subchronic administration of milnacipran produced significantly higher basal levels of extracellular noradrenaline. Acute milnacipran administration following subchronic milnacipran treatment for 7 days produced a greater increase in extracellular noradrenaline than a single dose of milnacipran alone. The present results suggest that subchronic milnacipran treatment enhances noradrenergic neural transmission beyond that achieved with acute administration of milnacipran alone, but has no effect on serotonergic or dopaminergic neural transmission. PMID:16153636

Kitaichi, Yuji; Inoue, Takeshi; Izumi, Takeshi; Nakagawa, Shin; Kato, Akiko; Koyama, Tsukasa



It's time to change the default for tobacco treatment.  


The World Health Organization estimates that 1 billion people will die from tobacco-related illnesses this century. Most health-care providers, however, fail to treat tobacco dependence. This may be due in part to the treatment 'default'. Guidelines in many countries recommend that health-care providers: (i) ask patients if they are 'ready' to quit using tobacco; and (ii) provide treatment only to those who state they are ready to quit. For other health conditions-diabetes, hypertension, asthma and even substance abuse-treatment guidelines direct health-care providers to identify the health condition and initiate evidence-based treatment. As with any medical care, patients are free to decline-they can 'opt out' from care. If patients do nothing, they will receive care. For tobacco users, however, the treatment default is often that they have to 'opt in' to treatment. This drastically limits the reach of tobacco treatment because, at any given encounter, a minority of tobacco users will say they are ready to quit. As a result, few are offered treatment. It is time to change the treatment default for tobacco dependence. All tobacco users should be offered evidence-based care, without being screened for readiness as a precondition for receiving treatment. Opt-out care for tobacco dependence is warranted because changing defaults has been shown to change choices and outcomes for numerous health behaviors, and most tobacco users want to quit; there is little to no evidence supporting the utility of assessing readiness to quit, and an opt-out default is more ethical. PMID:25323093

Richter, Kimber P; Ellerbeck, Edward F



Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury.  


Treatment of renal ischemia-reperfusion (IR) injury with recombinant human erythropoietin (rhEPO) reduces acute kidney injury and improves function. We aimed to investigate whether progression to chronic kidney disease associated with acute injury was also reduced by rhEPO treatment, using in vivo and in vitro models. Rats were subjected to bilateral 40-min renal ischemia, and kidneys were studied at 4, 7, and 28 days postreperfusion for renal function, tubular injury and repair, inflammation, and fibrosis. Acute injury was modulated using rhEPO (1,000 or 5,000 IU/kg, intraperitoneally) at the time of reperfusion. Renal tubular epithelial cells or fibroblasts in culture were subjected to hypoxia or oxidative stress, with or without rhEPO (200 IU/ml), and fibrogenesis was studied. The results of the in vivo model confirmed functional and structural improvement with rhEPO at 4 days post-IR (P < 0.05). At 7 days post-IR, fibrosis and myofibroblast stimulation were increased with IR with and without rhEPO (P < 0.01). However, at 28 days post-IR, renal fibrosis and myofibroblast numbers were significantly greater with IR plus rhEPO (P < 0.01) compared with IR only. Mechanistically, rhEPO stimulated profibrotic transforming growth factor-?, oxidative stress (marker 8-hydroxy-deoxyguanosine), and phosphorylation of the signal transduction protein extracellular signal-regulated kinase. In vitro, rhEPO protected tubular epithelium from apoptosis but stimulated epithelial-to-mesenchymal transition and also protected and activated fibroblasts, particularly with oxidative stress. In summary, although rhEPO was protective of renal function and structure in acute kidney injury, the supraphysiological dose needed for renoprotection contributed to fibrogenesis and stimulated chronic kidney disease in the long term. PMID:24402097

Gobe, Glenda C; Bennett, Nigel C; West, Malcolm; Colditz, Paul; Brown, Lindsay; Vesey, David A; Johnson, David W



Physical therapy treatment time during inpatient spinal cord injury rehabilitation  

PubMed Central

Background/objective To describe the nature and distribution of activities during physical therapy (PT) delivered in inpatient spinal cord injury (SCI) rehabilitation and discuss predictors (patient and injury characteristics) of the amount of time spent in PT for specific treatment activities. Methods Six hundred patients from six inpatient SCI centers were enrolled in the SCIRehab study. Physical therapists documented details, including time spent, of treatment provided during 37 306 PT sessions that occurred during inpatient SCI rehabilitation. Ordinary least squares regression models associated patient and injury characteristics with time spent in specific PT activities. Results SCIRehab patients received a mean total of 55.3 hours of PT over the course of their rehabilitation stay. Significant differences among four neurologic groups were seen in the amount of time spent on most activities, including the most common PT activities of strengthening exercises, stretching, transfer training, wheelchair mobility training, and gait training. Most PT work (77%) was provided in individual therapy sessions; the remaining 23% was done in group settings. Patient and injury characteristics explained only some of the variations seen in time spent on wheelchair mobility, transfer and bed mobility training, and range of motion/stretching. Conclusion Analysis yielded both expected and unexpected trends in SCI rehabilitation. Significant variation was seen in time spent on PT activities within and among injury groups. Providing therapeutic strengthening treatments consumed the greatest proportion of PT time. About one-quarter of all PT services were provided in group settings. Details about services provided, including time spent, will serve as a starting point in detailing the optimal treatment delivery for maximal outcomes. PMID:21675354

Taylor-Schroeder, Sally; LaBarbera, Jacqueline; McDowell, Shari; Zanca, Jeanne M.; Natale, Audrey; Mumma, Sherry; Gassaway, Julie; Backus, Deborah



Causal Inference for Time-Varying Instructional Treatments  

ERIC Educational Resources Information Center

The authors propose a strategy for studying the effects of time-varying instructional treatments on repeatedly observed student achievement. This approach responds to three challenges: (a) The yearly reallocation of students to classrooms and teachers creates a complex structure of dependence among responses; (b) a child's learning outcome under a…

Hong, Guanglei; Raudenbush, Stephen W.



Increased Use of Antipsychotic Long-Acting Injections with Community Treatment Orders  

PubMed Central

Background: Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. Aims: The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. Method: A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. Results: A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (?2 = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. Conclusions: There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle. PMID:23983926

Patel, Maxine X.; Matonhodze, Jane; Baig, Mirza K.; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S.



NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use.  


Studies in animals and humans show that blockade of nerve growth factor (NGF) attenuates both malignant and nonmalignant skeletal pain. While reduction of pain is important, a largely unanswered question is what other benefits NGF blockade might confer in patients with bone cancer. Using a mouse graft model of bone sarcoma, we demonstrate that early treatment with an NGF antibody reduced tumor-induced bone destruction, delayed time to bone fracture, and increased the use of the tumor-bearing limb. Consistent with animal studies in osteoarthritis and head and neck cancer, early blockade of NGF reduced weight loss in mice with bone sarcoma. In terms of the extent and time course of pain relief, NGF blockade also reduced pain 40% to 70%, depending on the metric assessed. Importantly, this analgesic effect was maintained even in animals with late-stage disease. Our results suggest that NGF blockade immediately upon detection of tumor metastasis to bone may help preserve the integrity and use, delay the time to tumor-induced bone fracture, and maintain body weight. PMID:25287160

McCaffrey, Gwen; Thompson, Michelle L; Majuta, Lisa; Fealk, Michelle N; Chartier, Stephane; Longo, Geraldine; Mantyh, Patrick W



Correcting radiation survey data to account for increased leakage during intensity modulated radiotherapy treatments  

SciTech Connect

Purpose: Intensity modulated radiotherapy (IMRT) treatments require more beam-on time and produce more linac head leakage to deliver similar doses to conventional, unmodulated, radiotherapy treatments. It is necessary to take this increased leakage into account when evaluating the results of radiation surveys around bunkers that are, or will be, used for IMRT. The recommended procedure of applying a monitor-unit based workload correction factor to secondary barrier survey measurements, to account for this increased leakage when evaluating radiation survey measurements around IMRT bunkers, can lead to potentially costly overestimation of the required barrier thickness. This study aims to provide initial guidance on the validity of reducing the value of the correction factor when applied to different radiation barriers (primary barriers, doors, maze walls, and other walls) by evaluating three different bunker designs.Methods: Radiation survey measurements of primary, scattered, and leakage radiation were obtained at each of five survey points around each of three different radiotherapy bunkers and the contribution of leakage to the total measured radiation dose at each point was evaluated. Measurements at each survey point were made with the linac gantry set to 12 equidistant positions from 0° to 330°, to assess the effects of radiation beam direction on the results.Results: For all three bunker designs, less than 0.5% of dose measured at and alongside the primary barriers, less than 25% of the dose measured outside the bunker doors and up to 100% of the dose measured outside other secondary barriers was found to be caused by linac head leakage.Conclusions: Results of this study suggest that IMRT workload corrections are unnecessary, for survey measurements made at and alongside primary barriers. Use of reduced IMRT workload correction factors is recommended when evaluating survey measurements around a bunker door, provided that a subset of the measurements used in this study are repeated for the bunker in question. Reduction of the correction factor for other secondary barrier survey measurements is not recommended unless the contribution from leakage is separately evaluated.

Kairn, T. [Premion Cancer Care, Wesley Medical Centre, Suite 1, 40 Chasely St, Auchenflower Qld 4066, Australia and Science and Engineering Faculty, Queensland University of Technology, G.P.O. Box 2434, Brisbane Qld 4000 (Australia)] [Premion Cancer Care, Wesley Medical Centre, Suite 1, 40 Chasely St, Auchenflower Qld 4066, Australia and Science and Engineering Faculty, Queensland University of Technology, G.P.O. Box 2434, Brisbane Qld 4000 (Australia); Crowe, S. B.; Trapp, J. V. [Science and Engineering Faculty, Queensland University of Technology, G.P.O. Box 2434, Brisbane Qld 4000 (Australia)] [Science and Engineering Faculty, Queensland University of Technology, G.P.O. Box 2434, Brisbane Qld 4000 (Australia)



Animal Study on Primary Dysmenorrhoea Treatment at Different Administration Times  

PubMed Central

The new methods of different administration times for the treatment of primary dysmenorrhea are more widely used clinically; however, no obvious mechanism has been reported. Therefore, an animal model which is closer to clinical evaluation is indispensable. A novel animal experiment with different administration times, based on the mice oestrous cycle, for primary dysmenorrhoea treatment was explored in this study. Mice were randomly divided into two parts (one-cycle and three-cycle part) and each part includes five groups (12 mice per group), namely, Jingqian Zhitong Fang (JQF) 6-day group, JQF last 3-day group, Yuanhu Zhitong tablet group, model control group, and normal control group. According to the one-way ANOVAs, results (writhing reaction, and PGF2?, PGE2, NO, and calcium ions analysis by ELISA) of the JQF cycle group were in accordance with those of JQF last 3-day group. Similarly, results of three-cycle continuous administration were consistent with those of one-cycle treatment. In conclusion, the consistency of the experimental results illustrated that the novel animal model based on mice oestrous cycle with different administration times is more reasonable and feasible and can be used to explore in-depth mechanism of drugs for the treatment of primary dysmenorrhoea in future. PMID:25705236

Pu, Bao-Chan; Fang, Ling; Gao, Li-Na; Liu, Rui; Li, Ai-zhu



Occupational therapy treatment time during inpatient spinal cord injury rehabilitation  

PubMed Central

Background Occupational therapy (OT) is a critical component of the rehabilitation process after spinal cord injury (SCI), the constitution of which has not been studied or documented in full detail previously. Objective To describe the type and distribution of SCI rehabilitation OT activities, including the amount of time spent on evaluation and treatment, and to discuss predictors (patient and injury characteristics) of the amount of time dedicated to OT treatment activities. Methods Six inpatient rehabilitation centers enrolled 600 patients with traumatic SCI in the first year of the SCIRehab. Occupational therapists documented 32 512 therapy sessions including time spent and specifics of each therapeutic activity. Analysis of variance and contingency tables/chi-square tests were used to test differences across neurologic injury groups for continuous and categorical variables. Results SCIRehab patients received a mean total of 52 hours of OT over the course of their rehabilitation stay. Statistically significant differences among four neurologic injury groups were seen in time spent on each OT activity. The activities that consumed the most OT time (individual and group sessions combined) were strengthening/endurance exercises, activities of daily living (ADLs), range of motion (ROM)/stretching, education, and a grouping of ‘therapeutic activities’ that included tenodesis training, fine motor activities, manual therapy, vestibular training, edema management, breathing exercise, cognitive retraining, visual/perceptual training desensitization, and don/doff adaptive equipment. Seventy-seven percent of OT work occurred in individual treatment sessions, with the most frequent OT activity involving ADLs. The variation in time (mean minutes per week) spent on OT ROM/stretching, ADLs, transfer training, assessment, and therapeutic activities can be explained in part by patient and injury characteristics, such as admission Functional Independence Measure (FIM) score, neurologic injury group, and the medical severity of illness score. Conclusion OT treatment patterns for patients with traumatic SCI show much variation in activity selection and time spent on activities, within and among neurologic level of injury groups. Some of the variation can be explained by patient and injury characteristics. Almost all patients with SCI participated in strengthening/endurance and ROM/stretching exercises during OT treatment and these two activities are where the most time was spent when therapy provided in individual and group settings was combined. ADL work consumed the most time in individual therapy sessions. PMID:21675355

Foy, Teresa; Perritt, Ginger; Thimmaiah, Deepa; Heisler, Lauren; Offutt, Jennifer Lookingbill; Cantoni, Kara; Hseih, Ching-Hui; Gassaway, Julie; Ozelie, Rebecca; Backus, Deborah



Behavioral procedures to increase cooperation of developmentally disabled children with dental treatment  

Microsoft Academic Search

This study evaluated the effectiveness of reinforcement procedures in increasing cooperation and reducing disruptive behavior during restorative dental treatment. Four mentally retarded children received praise and tokens for cooperating with direct requests From the dentist and for sitting quietly in the chair; tokens could later be exchanged for toys. A multiple-baseline, across-subjects design was used to assess levels of cooperation

Bruce J. Masek; Seth B. Canion; Michael F. Cataldo; Mary M. Riordan; B. Boe



Effect of heat treatment time on microstructure and electrical conductivity in LATP glass ceramics  

SciTech Connect

Glass-ceramic is prepared by heat treatment of melt quenched 14Li{sub 2}O?9Al{sub 2}O{sub 3}?38TiO{sub 2}?39P{sub 2}O{sub 5} glass in the vicinity of crystallization temperature. Growth of ceramic phase is controlled by tuning heat treatment time at fixed temperature. Ceramic phase was identified to be LiTi{sub 2}(PO{sub 4}){sub 3} from X Ray Diffraction analysis. Microstructural evolution of this phase with hold time was observed under high resolution Scanning Electron Microscope. DC conductivity is observed to increase by 4-5 orders of magnitude in this glass-ceramic compared to parent glass. However, formation of pores and cracks with very large heat treatment time seem to hinder further increase of conductivity.

Sonigra, Dhiren, E-mail:, E-mail:; Soman, Swati, E-mail:, E-mail:; Kulkarni, Ajit R., E-mail:, E-mail: [Dept. of Metallurgical Engineering and Materials Science, IIT Bombay, Mumbai-400076 (India)



Timing of Class III treatment with unfavorable growth pattern.  


When treating youngpatients with Class III malocclusion, factors such as timing and an accurate prediction of growth of the mandible are very important. Even though early interceptive treatment of Class III might often be successful, clinicians should be careful to not initiate early treatment with premolar extractions which will compromise the success of orthognathic surgery later due to mandibular prognathism. This case report presents an adolescent female patient who developed a severe Class III skeletal discrepancy during growth and was treated with surgery after her growth had finished. PMID:25571692

Tai, Kiyoshi; Park, Jae Hyun; Ohmura, Syuhei; Okadakage-Hayashi, Sakiko



Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity  

PubMed Central

Background The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment-based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases. Objective We measured the impact of 15–17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school-age children. Methods The prevalence of allergen skin test reactivity, exercise-induced bronchospasm and allergic symptoms was compared between school-age children living in communities that had received community-based treatments with ivermectin (for onchocerciasis control) for a period of 15–17 years with those living in geographically adjacent communities that had received no ivermectin. Results The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50–2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05–4.78, P=0.04) but not symptoms of asthma or rhino-conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections. Conclusion Long-term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino-conjunctivitis. Cite this as: P. Endara, M. Vaca, M. E. Chico, S. Erazo, G. Oviedo, I. Quinzo, A. Rodriguez R. Lovato, A.-L. Moncayo, M. L. Barreto, L. C. Rodrigues and P. J. Cooper, Clinical & Experimental Allergy, 2010 (40) 1669–1677. PMID:21039971

Endara, P; Vaca, M; Chico, M E; Erazo, S; Oviedo, G; Quinzo, I; Rodriguez, A; Lovato, R; Moncayo, A-L; Barreto, M L; Rodrigues, L C; Cooper, P J



Increased bcl-2 Protein Levels in Rat Primary Astrocyte Culture Following Chronic Lithium Treatment  

PubMed Central

Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium’s neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures. Methods: Rat primary astrocyte, neuronal, and mixed neuron-astrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively. Results: Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. Conclusion: Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium’s action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium’s action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder. PMID:24174697

Keshavarz, Mojtaba; Emamghoreishi, Masoumeh; Nekooeian, Ali Akbar; J. Warsh, Jerry; Zare, Hamid Reza



Rhein lysinate increases the median survival time of SAMP10 mice: protective role in the kidney  

PubMed Central

Aim: To investigate the protective effects of rhein lysinate (RHL), a major bioactive constituent of the rhizome of rhubarb (Rheum palmatum Linn or Rheum tanguticum Maxim), against kidney impairment in senescence-prone inbred strain 10 (SAMP10) mice. Methods: SAMP10 mice were orally administered RHL (25 or 50 mg/kg) daily until 50% of the mice died. Senescence-resistant inbred strain 1 (SAMR1) mice administered no drug were taken as control. The kidneys were harvested after animal death, and examined morphologically and with immunochemical assays. The levels of MAD, SOD and GSH-px in the kidneys were measured with a photometric method. The expression of inflammatory factors and related proteins in the kidneys was analyzed using Western blotting. Results: Treatment of SAMP10 mice with RHL had no effect on the body weight or phenotype. However, RHL significantly prolonged the median survival time of SAMP10 mice by approximately 25%, as compared to untreated SAMP10 mice. Compared SAMR1 mice, SAMP10 mice had a significantly lower level of SOD in the kidneys, but had no significant difference in the MDA or GSH-px levels. Treatment of SAMP10 mice with RHL significantly reduced the MAD level, and increased the SOD and GSH-px levels in the kidneys. Glomerulonephritis was observed in SAMP10 mice but not in SAMR1 mice. RHL decreased the incidence of glomerulonephritis, and significantly decreased the levels of TNF-?, IL-6, NF-?B, collagen types I and III in the kidneys. Conclusion: Accelerated senescence is associated with glomerulonephritis in SAMP10 mice, and RHL prolongs their median survival time by reducing the severity of glomerulonephritis. PMID:23474705

Hu, Gang; Liu, Jiang; Zhen, Yong-zhan; Xu, Rong; Qiao, Yu; Wei, Jie; Tu, Ping; Lin, Ya-jun



Increasing dependency of older people in nursing homes is associated with need for dental treatments  

PubMed Central

To determine relationships between the need for dental treatments of institutionalized elderly people and cognitive impairment and the general level of care needed. Two hundred and sixty-eight residents of long-term care facilities in Germany were included in this study. Age, sex, diseases, number of frequently taken drugs, and location of the long-term care facility of the participants were recorded. For each participant, the need for care was assessed by use of the Barthel index (BI). Cognitive impairment was evaluated by use of the mini-mental state examination (MMSE). To assess dental treatment needs, the revised oral assessment guide (ROAG) was applied for different oral health conditions, which were rated “healthy” or “treatment needed”. Spearman correlations were performed to evaluate associations between BI and MMSE and dental treatment needs. Statistical analysis revealed significant associations of BI (P<0.001) and MMSE (P=0.015) with the ROAG score. Increasing dependency and decreasing cognitive ability worsen oral health and increase the need for dental treatment. PMID:25506220

Zenthöfer, Andreas; Rammelsberg, Peter; Cabrera, Tomas; Hassel, Alexander Jochen



Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats  

PubMed Central

The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating. PMID:25610366

Dardou, David; Chassain, Carine; Durif, Franck



SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects.  


Clinical lore and a small number of published studies report that the selective serotonin reuptake inhibitors (SSRIs) intensify dreaming. This study examines the dream effects of paroxetine and fluvoxamine in order to both increase clinical knowledge of these agents and to test an important potential method for probing the relationship between REM sleep neurobiology and dreaming in humans. Fourteen normal, paid volunteers (4 males, 10 females; mean age 27.4 year, range 22--39) free of medical or neuropsychiatric symptoms as well as of psychotropic or sleep affecting drugs completed a 31-day home-based study consisting of: 7 days drug-free baseline; 19 days on either 100 mg fluvoxamine (7 Ss) or 20 mg paroxetine (7 Ss) in divided morning and evening doses; and 5 days acute discontinuation. Upon awakening, subjects wrote dream reports, self-scored specific emotions in their reports and rated seven general dream characteristics using 5-point Likert scales. Dream reports were independently scored for bizarreness, movement and number of visual nouns by three judges. REM sleep-related measures were obtained using the Nightcap ambulatory sleep monitor. Mean dream recall frequency decreased during treatment compared with baseline. Dream report length and judge-rated bizarreness were greater during acute discontinuation compared with both baseline and treatment and this effect was a result of the fluvoxamine-treated subjects. The subjective intensity of dreaming increased during both treatment and acute discontinuation compared with baseline. Propensity to enter REM sleep was decreased during treatment compared with baseline and acute discontinuation and the intensity of REM sleep increased during acute discontinuation compared with baseline and treatment. The decrease in dream frequency during SSRI treatment may reflect serotonergic REM suppression while the augmented report length and bizarreness during acute SSRI discontinuation may reflect cholinergic rebound from serotonergic suppression. PMID:11422727

Pace-Schott, E F; Gersh, T; Silvestri, R; Stickgold, R; Salzman, C; Hobson, J A




Technology Transfer Automated Retrieval System (TEKTRAN)

Recent data indicate that dietary modification may increase potential phosphorus (P) losses when manure is applied to pastures. This study was conducted to determine the effects of feed and manure treatments on P in soil with time. Manure was collected from studies of swine and poultry fed modified ...


Treatment options for symptomatic carotid stenosis: timing and approach.  


Stroke is a major cause of morbidity and mortality and up to 15-20% of ischemic strokes can be attributed to atherosclerotic internal carotid artery disease. The treatment of carotid artery disease has been the subject of a wealth of literature in the past twenty years since the publication of the landmark randomized controlled trials, the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial, in the early 1990s. Although these landmark trials have helped establish the current guidelines for treatment of patients with symptomatic carotid artery disease, there have since been major advancements in the medical treatment of cardiovascular disease and there still remains a great deal of controversy regarding the timing and technical approach to carotid revascularization. In particular, there has been a wealth of literature to determine whether carotid endarterectomy or carotid stenting should be used for revascularization and when this revascularization should occur following onset of symptoms. This update offers an overview of the standards for diagnosis and medical treatment of patients with symptomatic carotid artery disease, the indications for surgical revascularization and a review of the most pertinent literature as it pertains to the more controversial issues of technical approach and timing of surgical revascularization following onset of symptoms in patients with carotid artery disease. PMID:25439169

Vavra, Ashley K; Eskandari, Mark K



Tick bites and Lyme disease: the need for timely treatment.  


In the United States, 30,158 people were reported as having contracted Lyme disease during 2010; 96% of the cases in 2011 were reported from 13 northeast and north-central states. Time of tick attachment is a critical factor. Prolonged attachment allows time for a bacterium to move from tick to human. Patient history and meticulous skin inspection are the most important elements used in diagnosis of Lyme disease. The most common drug for treatment is doxycycline. Ticks find their hosts by several senses: odor, moisture, heat, and vibration. Avoidance of tick-infested areas, such as wooded areas and leaf piles, is paramount in preventing Lyme disease. PMID:23692936

Overstreet, Maria L



Overestimation of the second time interval replaces time-shrinking when the difference between two adjacent time intervals increases  

PubMed Central

When the onsets of three successive sound bursts mark two adjacent time intervals, the second time interval can be underestimated when it is physically longer than the first time interval by up to 100 ms. This illusion, time-shrinking, is very stable when the first time interval is 200 ms or shorter (Nakajima et al., 2004, Perception, 33). Time-shrinking had been considered a kind of perceptual assimilation to make the first and the second time interval more similar to each other. Here we investigated whether the underestimation of the second time interval was replaced by an overestimation if the physical difference between the neighboring time intervals was too large for the assimilation to take place; this was a typical situation in which a perceptual contrast could be expected. Three experiments to measure the overestimation/underestimation of the second time interval by the method of adjustment were conducted. The first time interval was varied from 40 to 280 ms, and such overestimations indeed took place when the first time interval was 80–280 ms. The overestimations were robust when the second time interval was longer than the first time interval by 240 ms or more, and the magnitude of the overestimation was larger than 100 ms in some conditions. Thus, a perceptual contrast to replace time-shrinking was established. An additional experiment indicated that this contrast did not affect the perception of the first time interval substantially: The contrast in the present conditions seemed unilateral. PMID:24860471

Nakajima, Yoshitaka; Hasuo, Emi; Yamashita, Miki; Haraguchi, Yuki



Photodynamic treatment of pooled coumarin plasma for external quality assessment of the prothrombin time  

PubMed Central

Aims—To determine the conditions of photodynamic inactivation of vesicular stomatitis virus (VSV) added to pooled coumarin plasma and the effects of the photodynamic treatment on the prothrombin times and international normalised ratio (INR) in a Netherlands national external quality assessment scheme. Methods—Pooled coumarin plasma samples were illuminated with visible light in the presence of 1 µM methylene blue. Inactivation conditions for VSV in pooled coumarin plasma were determined using an end point dilution assay. Plasma illuminated for 20 minutes was mixed with red blood cells and mailed to participants of the Netherlands external quality assessment (EQA) scheme. Prothrombin times and INRs were determined with various thromboplastin reagents. Results—Photodynamic treatment using 1 µM methylene blue and 700 W/m2 caused 4.7 log inactivation of VSV in pooled coumarin plasma. Fibrinogen and coagulation factors II, V, VII, and X were decreased slightly by the treatment. These conditions caused prolongation of the prothrombin time in EQA surveys. The magnitude of the effect was different for various thromboplastin reagents. The increase of the INR was negligible when measured with the Thrombotest reagent. With other reagents, an approximately 5–16% increase of the INR was observed. Interlaboratory variation of the INR was not affected by photodynamic treatment. Conclusions—Photodynamic treatment of pooled coumarin plasma is very effective for the inactivation of some enveloped viruses such as VSV, but has only a limited effect on the prothrombin time and INR. Photodynamic treatment can be used to improve the viral safety of coumarin plasma for EQA of the prothrombin time and INR. Key Words: prothrombin time • international normalised ratio • external quality assessment • photodynamic treatment PMID:10911807

van den Besselaar, A M H P; Moor, A



Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids  

PubMed Central

The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. The DOPAC+HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. PMID:10217522

Thiblin, Ingemar; Finn, Anja; Ross, Svante B; Stenfors, Carina



Adolescent silymarin treatment increases anxiety-like behaviors in adult mice.  


Adolescence is one of the most important periods of brain development in mammals. There is increasing evidence that some medicines during this period can affect brain and behavioral functions in adulthood. Silymarin (SM), a mixture of flavonolignans extracted from the milk thistle Silybum marianum, is known as a hepatoprotective, anti-inflammatory, and neuroprotective drug. Although researchers have extensively studied the effects of SM during adulthood, to date there is no information on the effects of this drug during the stages of brain development on behavioral functions in adulthood. In the current study, we investigated the effects of adolescent SM treatment on body weight and anxiety-like behaviors in adult male and female mice. Adolescent NMRI mice (postnatal day 30-50) were treated orally with water or SM (50 and 100 mg/kg). Animals were weighed during drug treatment and were then subjected to open field, elevated plus maze, and light-dark box tests from postnatal day 70. The results indicated that adolescent SM treatment increased anxiety-like behaviors in open field, elevated plus maze, and light-dark box in adult mice, while not altering body weight. Collectively, these findings suggest that adolescent SM treatment may have profound effects on the development of brain and behavior in adulthood. PMID:24978280

Kosari-Nasab, Morteza; Rabiei, Afshin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar



UV/ozone surface treatment increases hydrophilicity and enhances functionality of SU-8 photoresist polymer  

NASA Astrophysics Data System (ADS)

SU-8 photoresist polymer is widely used in the fabrication of microdevices. However, for biological applications, the problem of efficiently modifying SU-8 surfaces without perturbing roughness has not been successfully resolved. We present UV/ozone (UVO) surface pre-treatment as an effective method to increase the hydrophilicity of SU-8 films without affecting surface roughness, thus improving specific covalent binding of bio-molecules. We demonstrate that 30 s UVO treatment suffices to create carboxyl groups at the surface that can then be used for high density binding of molecules via amide bond formation. We further demonstrate that a two-step surface modification where the surface is first protected with an ethylene glycol monolayer leads to an increase in binding specificity. Finally, to illustrate the controlled binding and accessibility of immobilized molecules, we show three cycles of reversible interactions between anti-tamra antibody and tamra-cadaverine immobilized on the surface of SU-8.

Delplanque, Aleksandra; Henry, Etienne; Lautru, Joseph; Leh, Hervé; Buckle, Malcolm; Nogues, Claude



Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.  


Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A



Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue  

PubMed Central

Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r?=?0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.



Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project.  


Suicidal thoughts during antidepressant treatment have been the focus of several candidate gene association studies. The aim of the present genome-wide association study was to identify additional genetic variants involved in increasing suicidal ideation during escitalopram and nortriptyline treatment. A total of 706 adult participants of European ancestry, treated for major depression with escitalopram or nortriptyline over 12 weeks in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study were genotyped with Illumina Human 610-Quad Beadchips (Illumina, San Diego, CA, USA). A total of 244 subjects experienced an increase in suicidal ideation during follow-up. The genetic marker most significantly associated with increasing suicidality (8.28 × 10(-7)) was a single-nucleotide polymorphism (SNP; rs11143230) located 30?kb downstream of a gene encoding guanine deaminase (GDA) on chromosome 9q21.13. Two suggestive drug-specific associations within KCNIP4 (Kv channel-interacting protein 4; chromosome 4p15.31) and near ELP3 (elongation protein 3 homolog; chromosome 8p21.1) were found in subjects treated with escitalopram. Suggestive drug by gene interactions for two SNPs near structural variants on chromosome 4q12, one SNP in the apolipoprotein O (APOO) gene on chromosome Xp22.11 and one on chromosome 11q24.3 were found. The most significant association within a set of 33 candidate genes was in the neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene. Finally, we also found trend for an association within genes previously associated with psychiatric phenotypes indirectly linked to suicidal behavior, that is, GRIP1, NXPH1 and ANK3. The results suggest novel pathways involved in increasing suicidal ideation during antidepressant treatment and should help to target treatment to reduce the risk of this dramatic adverse event. Limited power precludes definitive conclusions and replication in larger sample is warranted. PMID:20877300

Perroud, N; Uher, R; Ng, M Y M; Guipponi, M; Hauser, J; Henigsberg, N; Maier, W; Mors, O; Gennarelli, M; Rietschel, M; Souery, D; Dernovsek, M Z; Stamp, A S; Lathrop, M; Farmer, A; Breen, G; Aitchison, K J; Lewis, C M; Craig, I W; McGuffin, P



Treatment with Insulin Analog X10 and IGF-1 Increases Growth of Colon Cancer Allografts  

PubMed Central

Obesity and type 2 diabetes are associated with an increased risk for development of certain forms of cancer, including colon cancer. The publication of highly controversial epidemiological studies in 2009 raised the possibility that use of the insulin analog glargine increases this risk further. However, it is not clear how mitogenic effects of insulin and insulin analogs measured in vitro correlate with tumor growth-promoting effects in vivo. The aim of this study was to examine possible growth-promoting effects of native human insulin, insulin X10 and IGF-1, which are considered positive controls in vitro, in a short-term animal model of an obesity- and diabetes-relevant cancer. We characterized insulin and IGF-1 receptor expression and the response to treatment with insulin, X10 and IGF-1 in the murine colon cancer cell line (MC38 cells) in vitro and in vivo. Furthermore, we examined pharmacokinetics and pharmacodynamics and monitored growth of MC38 cell allografts in mice with diet-induced obesity treated with human insulin, X10 and IGF-1. Treatment with X10 and IGF-1 significantly increased growth of MC38 cell allografts in mice with diet-induced obesity and we can therefore conclude that supra-pharmacological doses of the insulin analog X10, which is super-mitogenic in vitro and increased the incidence of mammary tumors in female rats in a 12-month toxicity study, also increase growth of tumor allografts in a short-term animal model. PMID:24260289

Hvid, Henning; Blouin, Marie-José; Birman, Elena; Damgaard, Jesper; Poulsen, Fritz; Fels, Johannes Josef; Fledelius, Christian; Hansen, Bo Falck; Pollak, Michael



Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women.  


Strenuously exercising young women with hypothalamic amenorrhea are hypoleptinemic and have low bone mineral density (BMD) and content (BMC), which predispose them to increased fracture risk. Short-term leptin replacement in these women corrects many neuroendocrine abnormalities and increases circulating levels of bone formation markers. Whether treatment with recombinant methionyl human leptin (metreleptin) for a long period improves BMD and BMC remains unknown. We studied 20 strenuously exercising young women with hypoleptinemia (leptin concentration <5 ng/mL) and hypothalamic amenorrhea of at least 6 months' duration. Eleven were randomized to metreleptin (initial dose, 0.08 mg/[kg·d] for 3 months; altered thereafter to 0.12 mg/kg for lack of efficacy or 0.04 mg/[kg d] for more than 5% weight loss) and 9 were randomized to placebo for 9 months. After a 3-month washout period, subjects were reexamined at the 1-year time point. Six subjects elected to continue on open-label metreleptin treatment for another 12 months. Two subjects dropped out after 18 months, and 4 completed the entire 2-year study. The BMD and BMC of the total body, lumbar spine (L1-L4), hip, and radius were assessed by using dual-energy x-ray absorptiometry at baseline and at 3, 6, 9, 12, 18, and 24 months of treatment. Metabolic and hormonal parameters and bone markers were measured in blood and urine. Metreleptin significantly increased BMC (P = .034) and tended to increase BMD (P = .069) at the lumbar spine at 9 months in the entire study group (intention-to-treat analysis). In subjects who completed the entire 2-year study (n = 4), metreleptin significantly increased BMD (P = .024) and BMC (P = .049) at the lumbar spine by 4% to 6%. Changes were not significant at the whole body, hip, and radius. Changes in hormonal and metabolic parameters and bone markers were moderate during the first year of treatment, but metreleptin further increased insulin-like growth factor 1 and decreased cortisol and cross-linked C-terminal telopeptide of type 1 collagen concentrations in serum during the second year of treatment (P < .05). The incremental area under the estradiol concentration curve over the 2-year course of the study correlated positively with the corresponding increase in lumbar spine BMD (? = 0.42, P = .039). Long-term metreleptin administration in strenuously exercising young women with hypothalamic amenorrhea and hypoleptinemia increases lumbar spine BMD and BMC and alters bone remodeling milieu to favor bone accretion. Results from this pilot study should be confirmed by future, larger clinical trials and need to be extended by studying bone microarchitecture and fracture risk. PMID:21741057

Sienkiewicz, Elizabeth; Magkos, Faidon; Aronis, Konstantinos N; Brinkoetter, Mary; Chamberland, John P; Chou, Sharon; Arampatzi, Kalliopi M; Gao, Chuanyun; Koniaris, Anastasia; Mantzoros, Christos S



Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression  

PubMed Central

Abnormal serotonin type 1A (5-HT1A) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([18F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action. PMID:23926239

Nugent, Allison C; Carlson, Paul J; Bain, Earle E; Eckelman, William; Herscovitch, Peter; Manji, Husseini; Zarate, Carlos A; Drevets, Wayne C



Real-time treatment feedback guidance of Pleural PDT  

NASA Astrophysics Data System (ADS)

Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma with remarkable results. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have improved the GUI of the light dose calculation engine to provide real-time light fluence distribution suitable for guiding the surgery to delivery light more uniformly. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings using both direct and scatter light models. An improved measurement device is developed to automatically acquire laser position for the point source. Comparison of the effects of the guidance is presented in phantom study.

Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Liu, Baochang; Meo, Julia L.; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Cengel, Keith; Friedberg, Joseph



Increase in oxidative stress as measured by cerebrospinal fluid lipid peroxidation during treatment for childhood acute lymphoblastic leukemia.  


Five-year survival from childhood acute lymphoblastic leukemia (ALL) approaches 90%, but 40% of survivors experience central nervous system (CNS) treatment-related cognitive problems. Despite considerable evidence for cognitive problems, less is known about mechanisms of neurological injury. Our purpose was to investigate oxidative stress, measured by lipid peroxidation, as a mechanism of CNS treatment-related neurological injury. The sample included 55 children (mean age at diagnosis=6.84 y, SD=3.40) who received intrathecal and intravenous chemotherapy for CNS-directed treatment according to Children's Oncology Group protocols. Glycerophospholipids were extracted from cerebrospinal fluid samples obtained at diagnosis and during intrathecal chemotherapy administration. Unoxidized and oxidized phosphatidylcholine (PC) and phosphatidylinositol (PI) were measured by normal phase high-performance liquid chromatography with diode array detection, and analyzed with a general linear model for repeated measures analysis of variance. Compared with the diagnostic cerebrospinal fluid sample, unoxidized and oxidized PC and PI increased significantly across treatment phases. Amount of intravenous methotrexate received was significantly correlated with oxidized PI, and age at time of ALL diagnosis was significantly associated with oxidized PC. These findings support our hypothesis that oxidative stress is a mechanism of neurological injury associated with CNS-directed treatment for ALL. PMID:25222054

Ki Moore, Ida M; Gundy, Patricia; Pasvogel, Alice; Montgomery, David W; Taylor, Olga A; Koerner, Kari M; McCarthy, Kathy; Hockenberry, Marilyn J



MD Anderson study shows new approach connecting smokers to quit lines increases smoking cessation treatment enrollment

Self-identified smokers directly connected to a tobacco cessation quit line are 13 times more likely to enroll in a treatment program as compared to smokers who are handed a quit line referral card and encouraged to call on their own, according to a new study led by researchers at the University of Texas MD Anderson Cancer Center and published online in JAMA Internal Medicine.


[Delays and treatment interruptions: difficulties in administering radiotherapy in an ideal time-period].  


Prescribed total radiation dose should be administered within in a specific time-frame and delays in commencing treatment and/or unplanned interruptions in radiation delivery are unacceptable because, in certain cancer sites, treatment-time prolongation can have a deleterious effect on local tumour control, and on patient outcomes. The present review evaluated the causes of initial treatment delays as well as interruptions in the scheduled radiotherapy. The literature search highlighted a significant concern in avoiding treatment-time prolongation in head and neck, cervix, breast and lung cancer. Among the causes involved in delay in radiotherapy commencement factors such as waiting lists, lack of material and human resources, and an increase complexity in planning, simulation and verification are highlighted. Most authors recommend radiotherapy commencement as soon as possible in radical (exclusive irradiation with active tumour present) and palliative situations with a maximum delay of no more than 6 to 8 weeks in the case of adjuvant radiotherapy (post-resection) programs. Interruptions during the course of treatment include: planned unit maintenance and servicing, acute patient toxicity or unexpected malfunction of linear accelerators; this last feature has the most deleterious effect on patients as well as radiotherapy practitioners. Interruptions that impact on the programmed time-course for radiotherapy needs to be compensated-for so as assure the biological equivalence in treatment efficacy with respect to cancer site and stage. PMID:15899208

González San Segundo, Carmen; Calvo Manuel, Felipe A; Santos Miranda, Juan Antonio



Teriparatide (PTH 1-34) treatment increases peripheral hematopoietic stem cells in postmenopausal women.  


Cells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B-cell development in animal models, perhaps via parathyroid hormone (PTH)-dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women. Twenty-three postmenopausal women at high risk of fracture received teriparatide 20 mcg sc daily for 24 months as part of a prospective longitudinal trial. Whole blood measurements were obtained at baseline, 3, 6, 12, and 18 months. Flow cytometry was performed to identify hematopoietic subpopulations, including HSCs (CD34+/CD45(moderate); ISHAGE protocol) and early transitional B cells (CD19+, CD27-, IgD+, CD24[hi], CD38[hi]). Serial measurements of spine and hip bone mineral density (BMD) as well as serum P1NP, osteocalcin, and CTX were also performed. The average age of study subjects was 64?±?5 years. We found that teriparatide treatment led to an early increase in circulating HSC number of 40%?±?14% (p?=?0.004) by month 3, which persisted to month 18 before returning to near baseline by 24 months. There were no significant changes in transitional B cells or total B cells over the course of the study period. In addition, there were no differences in complete blood count profiles as quantified by standard automated flow cytometry. Interestingly, the peak increase in HSC number was inversely associated with increases in bone markers and spine BMD. Daily teriparatide treatment for osteoporosis increases circulating HSCs by 3 to 6 months in postmenopausal women. This may represent a proliferation of marrow HSCs or increased peripheral HSC mobilization. This clinical study establishes the importance of PTH in the regulation of the HSC niche within humans. © 2014 American Society for Bone and Mineral Research. PMID:24420643

Yu, Elaine W; Kumbhani, Ruchit; Siwila-Sackman, Erica; DeLelys, Michelle; Preffer, Frederic I; Leder, Benjamin Z; Wu, Joy Y



A method to increase optical timing spectra measurement rates using a multi-hit TDC  

Microsoft Academic Search

A method is presented for using a modern time to digital converter (TDC) to increase the data collection rate for optical timing measurements such as scintillator decay times. It extends the conventional delayed coincidence method, where a synchronization signal ``starts'' a TDC and a photomultiplier tube (PMT) sampling the optical signal ``stops'' the TDC. Data acquisition rates are low with

W. W. Moses



Sexual risk behaviors increasing among adolescents over time: comparison of two cohorts in Spain.  


Despite advances in treatment and prevention, HIV/AIDS remains a serious health and social problem. This study's objective is to examine sexual behavior, levels of knowledge, and attitudes toward HIV/AIDS between two cohorts in Spanish adolescents, and to analyze gender differences in these cohorts. Participants were 2132 adolescents between 15 and 18 years of age: 1222 in 2006 (43.2% boys) and 910 in 2012 (54.1% boys). The results indicate lower HIV knowledge and less favorable attitudes about HIV/AIDS in the 2012 cohort. In addition, adolescents from the 2012 cohort had their first sexual intercourse at an earlier age and have more sexual partners than those from the 2006 cohort. Compared to boys, girls engage in fewer risky behaviors, although they did not use condoms with their stable partner; girls tended to use condom less when they were in a stable relationship than boys. This study confirms the insufficiency of prevention campaigns as well as the need to improve the impact from programs that promote healthy sexual habits. Assuming comparability of cohorts, this study suggests increased risk of HIV/AIDS over time. PMID:25587688

Espada, José P; Escribano, Silvia; Orgilés, Mireia; Morales, Alexandra; Guillén-Riquelme, Alejandro



Post-Injury Treatment with Rolipram Increases Hemorrhage After Traumatic Brain Injury  

PubMed Central

The pathology caused by traumatic brain injury (TBI) is exacerbated by the inflammatory response of the injured brain. Two pro-inflammatory cytokines that contribute to inflammation after TBI are tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). In previous studies using the parasagittal fluid-percussion brain injury model, we reported that the anti-inflammatory drug rolipram, a phosphodiesterase 4 inhibitor, reduced TNF-? and IL-1? levels and improved histopathological outcome when administered 30 min prior to injury. We now report that treatment with (±)-rolipram given 30 min after injury significantly reduced TNF-? levels in the cortex and hippocampus. However, post-injury administration of (±)-rolipram significantly increased cortical contusion volume and increased atrophy of the cortex as compared to vehicle-treated animals at 10 days post-injury. Thus, despite the reduction in pro-inflammatory cytokine levels, histopathological outcome was worsened with post-TBI (±)-rolipram treatment. Further histological analysis of (±)-rolipram-treated TBI animals revealed significant hemorrhage in the contused brain. Given the well known role of (±)-rolipram to increase vasodilation, it is likely that (±)-rolipram worsened outcome after fluid-percussion brain injury by causing increased bleeding. PMID:22535545

Atkins, C.M.; Kang, Y.; Furones, C.; Truettner, J.S.; Alonso, O.F.; Dietrich, W.D.



FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment  

PubMed Central

Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced ?2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes. PMID:25299696

Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E.



Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?  

PubMed Central

Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP) and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost savings due to high adherence. PMID:24711696

Kaiser, Edelgard Anna; Lotze, Ulrich; Schäfer, Hans Hendrik



PTH(1-34) Treatment Increases Bisphosphonate Turnover in Fracture Repair in Rats.  


Bisphosphonates (BP) are a class of anti-resorptive drugs with a high affinity for bone. Despite the therapeutic success in treating osteoporosis and metabolic bone diseases, chronic BP usage has been associated with reduced repair of micro-damage and atypical femoral fracture (AFF). The latter has a poor prognosis and while anabolic interventions such as Teriparatide (PTH (1-34) ) have been suggested as treatment options there is a limited evidence base in support of their efficacy. As PTH (1-34) acts to increase bone turnover, we hypothesized that it may be able to increase BP in turnover in the skeleton, which in turn may improve bone healing. To test this we employed a mixture of fluorescent Alexa647 labelled Pamidronate (Pam) and radiolabelled (14) C-ZA (zoledronic acid). These traceable BPs were dosed to Wistar rats in models of normal growth and closed fracture repair. Rats were co-treated with saline or 25?g/kg/d PTH(1-34) and the effects on BP liberation and bone healing, bones were examined by X-ray, microCT, autoradiography, and fluorescent confocal microscopy. Consistent with increased BP remobilization with PTH(1-34) there was a significant decrease in fluorescence in both the long bones and in the fracture callus in treated animals compared to controls. This was further confirmed by autoradiography for (14) C-ZA. In this model of acute BP treatment, callus bone volume (BV) was significantly increased in fractured limbs, and although we noted significant decreases in callus-bound BP with PTH(1-34) , these were not sufficient to alter this BV. However, increased intracellular BP was noted in resorbing osteoclasts confirming that, in principle, PTH(1-34) increases bone turnover as well as BP turnover. This article is protected by copyright. All rights reserved. PMID:25484198

Murphy, Ciara M; Schindeler, Aaron; Cantrill, Laurence C; Mikulec, Kathy; Peacock, Lauren; Little, David G



Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy  

PubMed Central

Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315



Increase in platelet immunoglobulin in Alzheimer's disease is normalised following cholinesterase inhibitor treatment: preliminary results.  


We report a 16.5% increase in platelet immunoglobulin (Ig) content in subjects with Alzheimer's disease (AD) in relation to cognitively intact individuals (p = 0.021), whereas the plasma Ig levels were unaltered (p = 0.428). The upregulation of platelet Ig was not explained by age, duration of dementia, or degree of cognitive impairment. However, AD subjects treated with cholinesterase inhibitors (n = 21) had lower levels of platelet Ig (p = 0.009) than AD subjects not treated with anti-dementia drugs (n = 4) and similar to those of control subjects (n = 24; p = 0.069). The anti-dementia treatment did not influence the plasma Ig levels (p = 0.177). These preliminary findings require further confirmation in studies on larger number of AD subjects with various stages of cognitive impairment, and who would be assessed prior to initiation of and during cholinesterase inhibitor treatment. PMID:22810090

Mukaetova-Ladinska, Elizabeta B; Abdel-All, Zeinab; Andrade, Joana; McNally, Richard J Q; James, Peter W; Kalaria, Raj N; O'Brien, John T



An investigation on sol-gel treatment to aramid yarn to increase inter-yarn friction  

NASA Astrophysics Data System (ADS)

Inter-yarn friction helps to increase energy absorption in ballistic fabrics. This paper reports on the results of sol-gel treatment on aramid yarns to increase the inter-yarn friction. Two types of TiO2/ZnO hydrosols (submicro-sized and nano-sized) prepared using hydrolysis and peptization methods were used to treat aramid yarns with and without curing. SEM was used to characterize the change in morphology. FTIR and EDX analyses were applied to identify the coating substance. The inter-yarn friction was tested using Capstan method. Images from SEM showed that the surface of the yarn treated with TiO2/ZnO submicro-sized hydrosol was covered with lump-like coating whilst in the case of TiO2/ZnO nano-sized sol treatment, the coating on the fibres was more film-like. The substance in the coating was confirmed as titanium dioxide and zinc oxide by FTIR and EDX analyses. The test results for coefficient of friction revealed that the coefficient of friction between the yarns treated by submicro-sized hydrosol was 54% higher than the non-treated, and the nano-sized hydrosol was associated to a 10% increase. However, the curing process had little effect on the coefficient of friction between yarns. The study also showed that the tensile properties of the treated yarns and the weight add-on were not significantly affected.

Chu, Yanyan; Chen, Xiaogang; Wang, Qing; Cui, Shizhong



Increased vertical dimension of occlusion: signs, symptoms, diagnosis, treatment and options.  


During the planning of oral rehabilitation, the vertical dimension of occlusion (VDO) is one of the first parameters to be measured since its improper restoration can lead to the failure of any prosthetic rehabilitation. A decreased VDO can lead to the appearance of lesions, such as angular cheilitis, facial disharmony, and temporomandibular disorders; meanwhile, an increased VDO may lead to the onset of joint and muscle pain, tension in functional speech, difficulty in swallowing, impaired chewing, tooth sensitivity due to traumatogenic forces, pathologic bone resorption, abnormal wearing of teeth, the appearance of an elongated face, and a facial expression of fatigue. Most scientific articles deal with methods and techniques for re-establishing VDO in edentulous patients or those who have lost their tooth reference due to prosthetic preparations. However, patients with increased VDO are also found in everyday practice. One treatment option for these patients is occlusal adjustment by selective tooth wear; it is still possible to perform orthodontic intrusion and/or orthognathic surgery in severe cases. The aim of this study was to discuss signs, symptoms, diagnosis, and treatment, and to report a clinical case of a patient with increased VDO. PMID:23579908

Discacciati, José Augusto César; Lemos de Souza, Eduardo; Vasconcellos, Walison Arthuso; Costa, Sérgio Carvalho; Barros, Vinícius de Magalhães



Increasing Physicians' and Nurses' Compliance with Treatment Guidelines in Cancer Care Program.  

ERIC Educational Resources Information Center

The effect of the use of guidelines on the care of patients with breast, colon, and non-small-cell lung cancers is reported. Audits of patient records revealed an increase over time in the percentage of recommended cancer care procedures that were complied with. (Author/MLW)

Slenker, Suzanne E.; And Others



Quiet-time electron increases, a measure of conditions in the outer solar system  

NASA Technical Reports Server (NTRS)

One possible explanation for quiet-time electron increases, increases in the intensity of 3-12 MeV interplanetary electrons that have been reported by McDonald, Cline and Simnett, is discussed. It is argued that the electrons in quiet-time increases are galactic in origin, but that the observed increases are not the result of any variation in the modulation of these particles in the inner solar system. It is suggested instead that quiet-time increases may occur when more electrons than normal penetrate a modulating region that lies far beyond the orbit of earth. The number of electrons penetrating this region may increase when field lines that have experienced an unusually large random walk in the photosphere are carried by the solar wind out to the region. As evidence for this increased random walk, it is shown that five solar rotations before most of the quiet-time increases there is an extended period when the amplitude of the diurnal anisotropy, as is measured by the Deep River neutron monitor, is relatively low. Five rotations delay time implies that the proposed modulating region lies at approximately 30 AU from the Sun, assuming that the average solar wind speed is constant over this distance at approximately 400 km/sec.

Fisk, L. A.; Vanhollebeke, M.



Efficient scheduling to reduce setup times and increase utilization in a multiple-part manufacturing system  

E-print Network

Two scheduling procedures were developed to reduce the total setup time and increase utilization in a multiple-part-type manufacturing system with sequence-dependent setups. These scheduling systems focus on reducing setup ...

Puszko, Gregory D



Combined Treatment with Interleukin-12 and Indomethacin Promotes Increased Resistance in BALB/c Mice with Established Leishmania major Infections  

PubMed Central

Following infection of susceptible BALB/c mice with Leishmania major, early production of interleukin-4 (IL-4) is associated with the development of a nonprotective Th2 response and the development of progressive disease. Treatment of mice with IL-12 at the time of infection can promote the activation of a protective Th1 response; however, IL-12 treatment of mice with established infections has little effect on the progress of lesion development. This may be due to a down-regulation of the IL-12 receptor ?2 chain (IL-12R?2) that accompanies the expansion of IL-4-producing Th2 cells. We have examined whether prostaglandins function to regulate in vivo responsiveness to IL-12. Mice treated with indomethacin are responsive to treatment with exogenous IL-12 through at least the first 2 weeks of infection and, unlike control mice treated with IL-12, develop an enhanced Th1-type response associated with increased enhanced resistance to infection. Cells from indomethacin-treated mice also exhibit enhanced production of gamma interferon (IFN-?) following in vitro stimulation with IL-12. Although in vivo indomethacin treatment did not appear to influence IL-12 production in infected mice, cells from indomethacin-treated mice did express higher levels of IL-12R?2, suggesting that prostaglandins may play a role in the loss of IL-12 responsiveness observed during nonhealing L. major infections. PMID:12228301

Li, Jian; Padigel, Udaikumar M.; Scott, Phillip; Farrell, Jay P.



Increasing the creation yield of shallow single defects in diamond by surface plasma treatment  

NASA Astrophysics Data System (ADS)

Single Nitrogen-Vacancy (NV) centers in diamond close to the crystal surface are very promising magnetic field sensors with very high sensitivity. Here, we report the enhanced creation of very shallow (less than 3 nm below the diamond surface) NV centers by using fluorine and oxygen plasma treatment. We observe a four fold increase—from 0.11% to about 0.45% in the production yield when the sample surface is terminated with fluorine or oxygen atoms. This effect is explained by the stabilization of the NV's negative charge state which is influenced by the various defects present on the diamond surface.

Osterkamp, Christian; Scharpf, Jochen; Pezzagna, Sebastien; Meijer, Jan; Diemant, Thomas; Jürgen Behm, Rolf; Naydenov, Boris; Jelezko, Fedor



Increased serum hepcidin levels during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndrome.  


Hepcidin is a major regulator of iron metabolism. We evaluated changes in serum hepcidin during 3 months of therapy with the iron-chelator deferasirox in patients with low-risk myelodysplastic syndrome and iron overload. Serum hepcidin was found to be high in these patients, correlated with their iron and oxidative status, and further increased by treatment with deferasirox. These findings support the concept that the hepcidin level represents a balance between the stimulating effect of iron overload and the inhibitory effects of erythropoietic activity and oxidative stress. These preliminary findings favour the rationale for iron chelation therapy in such patients. PMID:21332711

Ghoti, Hussam; Fibach, Eitan; Westerman, Mark; Gordana, Olbina; Ganz, Tomas; Rachmilewitz, Eliezer A



Increasing the creation yield of shallow single defects in diamond by surface plasma treatment  

SciTech Connect

Single Nitrogen-Vacancy (NV) centers in diamond close to the crystal surface are very promising magnetic field sensors with very high sensitivity. Here, we report the enhanced creation of very shallow (less than 3 nm below the diamond surface) NV centers by using fluorine and oxygen plasma treatment. We observe a four fold increase—from 0.11% to about 0.45% in the production yield when the sample surface is terminated with fluorine or oxygen atoms. This effect is explained by the stabilization of the NV's negative charge state which is influenced by the various defects present on the diamond surface.

Osterkamp, Christian; Scharpf, Jochen; Naydenov, Boris; Jelezko, Fedor [Institut für Quantenoptik, Ulm University, Albert Einstein Allee 11, Ulm 89081 (Germany)] [Institut für Quantenoptik, Ulm University, Albert Einstein Allee 11, Ulm 89081 (Germany); Pezzagna, Sebastien; Meijer, Jan [Institut für Experimentelle Physik II, Abteilung Nukleare Festkörperphysik, Universität Leipzig, Linnestraße 5, Leipzig 04103 (Germany)] [Institut für Experimentelle Physik II, Abteilung Nukleare Festkörperphysik, Universität Leipzig, Linnestraße 5, Leipzig 04103 (Germany); Diemant, Thomas; Jürgen Behm, Rolf [Institut für Oberflächenchemie und Katalyse, Ulm University, Albert-Einstein-Allee 47, Ulm 89081 (Germany)] [Institut für Oberflächenchemie und Katalyse, Ulm University, Albert-Einstein-Allee 47, Ulm 89081 (Germany)



Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.  


Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

Hove, Michael J; Keller, Peter E



Do increasing rates of loss to follow-up in antiretroviral treatment programs imply deteriorating patient retention?  


In several studies of antiretroviral treatment (ART) programs for persons with human immunodeficiency virus infection, investigators have reported that there has been a higher rate of loss to follow-up (LTFU) among patients initiating ART in recent years than among patients who initiated ART during earlier time periods. This finding is frequently interpreted as reflecting deterioration of patient retention in the face of increasing patient loads. However, in this paper we demonstrate by simulation that transient gaps in follow-up could lead to bias when standard survival analysis techniques are applied. We created a simulated cohort of patients with different dates of ART initiation. Rates of ART interruption, ART resumption, and mortality were assumed to remain constant over time, but when we applied a standard definition of LTFU, the simulated probability of being classified LTFU at a particular ART duration was substantially higher in recently enrolled cohorts. This suggests that much of the apparent trend towards increased LTFU may be attributed to bias caused by transient interruptions in care. Alternative statistical techniques need to be used when analyzing predictors of LTFU--for example, using "prospective" definitions of LTFU in place of "retrospective" definitions. Similar considerations may apply when analyzing predictors of LTFU from treatment programs for other chronic diseases. PMID:25399412

Johnson, Leigh F; Estill, Janne; Keiser, Olivia; Cornell, Morna; Moolla, Haroon; Schomaker, Michael; Grimsrud, Anna; Davies, Mary-Ann; Boulle, Andrew



Covariate Adjustment Strategy Increases Power in the Randomized Controlled Trial With Discrete-Time Survival Endpoints  

ERIC Educational Resources Information Center

In a randomized controlled trial, a decision needs to be made about the total number of subjects for adequate statistical power. One way to increase the power of a trial is by including a predictive covariate in the model. In this article, the effects of various covariate adjustment strategies on increasing the power is studied for discrete-time

Safarkhani, Maryam; Moerbeek, Mirjam



Short-term nutritional treatments grazing legumes or feeding concentrates increase prolificacy in Corriedale ewes.  


We tested whether short periods of increased nutrition will improve ovulation rate and prolificacy, irrespective of the method used to synchronise the cycles of the ewes. In Experiment 1, we used 138 Corriedale ewes to evaluate two factors: synchronization treatment (sponges versus a single injection of prostaglandin) and type of pasture (native versus improved with Lotus corniculatus). Ewes were mated at the end of the grazing period and prolificacy was evaluated at lambing. Grazing Lotus corniculatus for 12 days tended to increase the number of twin lambs born (P=0.09). The percentage of ewes showing oestrus during a 9-day period was similar among synchronization treatments. Animals in Experiments 2 (n=282) and 3 (n=288) were allocated to a control group or a group fed a supplement of corn grain and soybean meal for 7 days. Ewes received 2 prostaglandin injections and the supplement was fed from Days 11 to 17 after the second prostaglandin. Ovulation rate was measured in 65 (Experiment 2) and 61 (Experiment 3) ewes that were confirmed to have consumed the supplement and showed oestrus in a 4-day period. The supplement increased ovulation rate by 14% in both experiments (P<0.05). We conclude that Corriedale ewes can respond with increases in prolificacy to a 12-day period grazing Lotus corniculatus and in ovulation rate to 7 days feeding with a supplement rich in energy and protein. Moreover, in these studies, prostaglandin was as effective as sponges for synchronising oestrus, an important factor in future decisions about hormonal management of fertility. PMID:18639397

Viñoles, C; Meikle, A; Martin, G B



Application of time transfer function to McVittie spacetime: gravitational time delay and secular increase in astronomical unit  

NASA Astrophysics Data System (ADS)

We attempt to calculate the gravitational time delay in a time-dependent gravitational field, especially in McVittie spacetime, which can be considered as the spacetime around a gravitating body such as the Sun, embedded in the FLRW (Friedmann-Lemaître-Robertson-Walker) cosmological background metric. To this end, we adopt the time transfer function method proposed by Le Poncin-Lafitte et al. (Class Quantum Gravity 21:4463, 2004) and Teyssandier and Le Poncin-Lafitte (Class Quantum Gravity 25:145020, 2008), which is originally related to Synge's world function ?( x A , x B ) and enables to circumvent the integration of the null geodesic equation. We re-examine the global cosmological effect on light propagation in the solar system. The round-trip time of a light ray/signal is given by the functions of not only the spacial coordinates but also the emission time or reception time of light ray/signal, which characterize the time-dependency of solutions. We also apply the obtained results to the secular increase in the astronomical unit, reported by Krasinsky and Brumberg (Celest Mech Dyn Astron 90:267, 2004), and we show that the leading order terms of the time-dependent component due to cosmological expansion is 9 orders of magnitude smaller than the observed value of dAU/ dt, i.e., 15 ± 4 (m/century). Therefore, it is not possible to explain the secular increase in the astronomical unit in terms of cosmological expansion.

Arakida, Hideyoshi



Increasing the Amount of Time on Task for Kindergarten Students through the Use of Learning Styles.  

ERIC Educational Resources Information Center

This report describes a 12-week program designed to increase time on task for kindergarten students. Members of a targeted group of kindergarten students were identified as being off task an average of 1.9 times more than the rest of the class. A program that incorporated the dominant learning styles of students in the target group with…

Vallarta, Carolyn R.


Increasing On-Task Behavior Using Teacher Attention Delivered on a Fixed-Time Schedule  

ERIC Educational Resources Information Center

The effectiveness of fixed-time delivery of attention to increase the on-task behavior of 2 students in general education was examined. The teacher in this study provided attention to students on a 5-min fixed-time schedule and responded to students in her typical manner between cued intervals. An ABAB withdrawal design was used to test the…

Riley, Jessica L.; McKevitt, Brian C.; Shriver, Mark D.; Allen, Keith D.



Timing and decision-making in the treatment of congenital upper extremity deformities.  


With growth and development, the hand undergoes profound structural and functional changes. Congenital anomalies lead to development of aberrant functional patterns. Appropriate timing of surgical correction is essential to minimize deformity and prevent development of aberrant function before set patterns of cortical control have occurred. By the same token, certain anomalies should not be treated surgically since such treatment may interfere with function. A clearer understanding of pathologic anatomy of deformities such as radial club hand, hypoplastic thumb, and thumb duplication has enabled a more rational surgical approach. Microsurgery has an increasing role to play in the treatment of these deformities. PMID:2406090

Netscher, D T; Scheker, L R



Development of equations to determine the increase in pavement condition due to treatment and the rate of decrease in condition after treatment for a local agency pavement network.  

E-print Network


Deshmukh, Maithilee Mukund.



Increased pond depth improves algal productivity and nutrient removal in wastewater treatment high rate algal ponds.  


Depth has been widely recognised as a crucial operational feature of a high rate algal pond (HRAP) as it modifies the amount of light and frequency at which microalgal cells are exposed to optimal light. To date, there has been little focus on the optimisation of microalgal performance in wastewater treatment HRAPs with respect to depth, with advice ranging from as shallow as possible to 100 cm deep. This paper investigates the seasonal performance of microalgae in wastewater treatment HRAPs operated at three different depths (200, 300 and 400 mm). Microalgal performance was measured in terms of biomass production and areal productivity, nutrient removal efficiency and photosynthetic performance. The overall areal productivity significantly increased with increasing depth. Areal productivity ranged from 134 to 200% higher in the 400 mm deep HRAP compared to the 200 mm deep HRAP. Microalgae in the 400 mm deep HRAP were more efficient at NH4-N uptake and were photosynthetically more efficient compared to microalgae in the 200 mm deep HRAP. A higher chlorophyll-a concentration in the 200 mm deep HRAP resulted in a decrease in photosynthetic performance, due to insufficient carbon supply, over the course of the day in summer (as indicated by lower ?, Pmax and oxygen production) compared to the 300 and 400 mm deep HRAPs. Based on these results, improved areal productivity and more wastewater can be treated per land area in the 400 mm deep HRAPs compared to 200 mm deep HRAPs without compromising wastewater treatment quality, while lowering capital and operational costs. PMID:24530547

Sutherland, Donna L; Turnbull, Matthew H; Craggs, Rupert J



The role of temperature increase rate in combinational hyperthermia chemotherapy treatment  

NASA Astrophysics Data System (ADS)

Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

Tang, Yuan; McGoron, Anthony J.



Effect of enzyme concentration, addition of water and incubation time on increase in yield of starch from potato.  


Enzymatic treatment process for starch extraction from potato was investigated using cellulase enzyme and compared with conventional process. The effects of three parameters, cellulase enzyme concentration, incubation time and addition of water were evaluated for increase in starch yield as compared to the conventional process i.e., without using enzyme. A two-level full factorial design was used to study the process. The results indicated that all the main parameters and their interactions are statistically significant. Enzyme concentration and incubation time had a positive effect on the increase in starch yield while addition of water had a negative effect. The increase in starch yield ranged from 1.9% at low enzyme concentration and incubation time and high addition of water to a maximum of 70% increase from conventional process in starch yield was achieved when enzyme concentration and incubation time were high and addition of water was low suggesting water present in the ground potato meal is sufficient for access to the enzyme with in the slurry ensuring adequate contact with the substrate. PMID:24803713

Sit, Nandan; Agrawal, U S; Deka, Sankar C



A system for EPID-based real-time treatment delivery verification during dynamic IMRT treatment  

SciTech Connect

Purpose: To design and develop a real-time electronic portal imaging device (EPID)-based delivery verification system for dynamic intensity modulated radiation therapy (IMRT) which enables detection of gross treatment delivery errors before delivery of substantial radiation to the patient.Methods: The system utilizes a comprehensive physics-based model to generate a series of predicted transit EPID image frames as a reference dataset and compares these to measured EPID frames acquired during treatment. The two datasets are using MLC aperture comparison and cumulative signal checking techniques. The system operation in real-time was simulated offline using previously acquired images for 19 IMRT patient deliveries with both frame-by-frame comparison and cumulative frame comparison. Simulated error case studies were used to demonstrate the system sensitivity and performance.Results: The accuracy of the synchronization method was shown to agree within two control points which corresponds to approximately ?1% of the total MU to be delivered for dynamic IMRT. The system achieved mean real-time gamma results for frame-by-frame analysis of 86.6% and 89.0% for 3%, 3 mm and 4%, 4 mm criteria, respectively, and 97.9% and 98.6% for cumulative gamma analysis. The system can detect a 10% MU error using 3%, 3 mm criteria within approximately 10 s. The EPID-based real-time delivery verification system successfully detected simulated gross errors introduced into patient plan deliveries in near real-time (within 0.1 s).Conclusions: A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

Fuangrod, Todsaporn [Faculty of Engineering and Built Environment, School of Electrical Engineering and Computer Science, the University of Newcastle, NSW 2308 (Australia)] [Faculty of Engineering and Built Environment, School of Electrical Engineering and Computer Science, the University of Newcastle, NSW 2308 (Australia); Woodruff, Henry C.; O’Connor, Daryl J. [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308 (Australia)] [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308 (Australia); Uytven, Eric van; McCurdy, Boyd M. C. [Division of Medical Physics, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9 (Canada) [Division of Medical Physics, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9 (Canada); Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Department of Radiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Kuncic, Zdenka [School of Physics, University of Sydney, Sydney, NSW 2006 (Australia)] [School of Physics, University of Sydney, Sydney, NSW 2006 (Australia); Greer, Peter B. [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308, Australia and Department of Radiation Oncology, Calvary Mater Newcastle Hospital, Locked Bag 7, Hunter region Mail Centre, Newcastle, NSW 2310 (Australia)] [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308, Australia and Department of Radiation Oncology, Calvary Mater Newcastle Hospital, Locked Bag 7, Hunter region Mail Centre, Newcastle, NSW 2310 (Australia)



Predicting posttreatment cocaine abstinence for first-time admissions and treatment repeaters.  

PubMed Central

OBJECTIVES: This study examined client and program characteristics that predict posttreatment cocaine abstinence among cocaine abusers with different treatment histories. METHODS: Cocaine abusers (n = 507) treated in 18 residential programs were interviewed at intake and 1-year follow-up as part of the nationwide Drug Abuse Treatment Outcome Study (DATOS). Program directors provided the program-level data in a mail survey. We applied the hierarchical linear modeling approach for the analysis. RESULTS: No prior treatment and longer retention in DATOS programs were positive predictors of posttreatment abstinence. The interactive effect of these 2 variables was also significantly positive. Program that offered legal services and included recovering staff increased their clients' likelihood of cocaine abstinence. Crack use at both the client and program level predicted negative impact. None of the program variables assessed differentially affected the outcomes of first-timers and repeaters. CONCLUSIONS: Although treatment repeaters were relatively difficult to treat, their likelihood of achieving abstinence was similar to that of first-timers if they were retained in treatment for a sufficient time. First-timers and repeaters responded similarly to the treatment program characteristics examined. The treatment and policy implications of these findings are discussed. PMID:10224976

Hser, Y I; Joshi, V; Anglin, M D; Fletcher, B



Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment  

PubMed Central

Background: The benefit of adjuvant therapy in curatively resected lymph node-positive colon cancer was established using 5-fluorouracil (5-FU) and levamisole (LEV) for 12 months. 5-FU cytotoxicity can be modulated by folinic acid (FA) or interferon-? (INF-?). The aim of this study was to investigate the efficacy of modulating 5-FU+ LEV by either FA or IFN-? in the adjuvant treatment of high-risk colon cancer. Methods: Patients with curatively resected colon cancer (stages UICC IIb and III) were stratified according to T, N, and participating center and randomized to receive a 12-month treatment using 5-FU + LEV alone or in combination with FA or IFN-?. Results: A total of 855 of 904 entered patients (94.6%) were eligible. The median follow-up of all eligible patients was 4.6 years. Addition of FA to 5-FU + LEV improved recurrence-free and overall survival in comparison with 5-FU + LEV alone (P = 0.007 and P = 0.004, respectively, 1-sided). The 5-year overall survival rates were 60.5% (95% confidence interval, 54.3–66.7) and 72.0% (95% confidence interval, 66.5–77.5) for 5-FU + LEV and 5-FU + LEV + FA, respectively. Addition of INF-? showed a tendency to improve recurrence-free survival, however, without altering overall survival. Toxicities (WHO III + IV) were generally tolerable except one toxic death in the control arm and were observed in 9.9% of the patients receiving 5-FU + LEV alone and in 13.3% and in 30.7% of patients receiving additional FA and IFN-?, respectively. Conclusions: Addition of IFN-? was associated with increased toxicity without markedly influencing the outcome and should therefore not be recommended for adjuvant treatment. Addition of FA increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points, respectively. 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer. PMID:16041207

Link, Karl-Heinz; Kornmann, Marko; Staib, Ludger; Redenbacher, Martin; Kron, Martina; Beger, Hans Günter



Evaluation of pre-treatment processes for increasing biodegradability of agro-food wastes.  


Anaerobic digestion (AD) technology can be employed for treating sewage sludge, livestock waste or food waste. Generally, the hydrolysis stage is the rate-limiting step of the AD processes for solid waste degradation. Therefore, physical, chemical and biological pre-treatment methods or their combination are required, in order to reduce the rate of such a limiting step. In this study, four methods (mechanical shredding, acid hydrolysis, alkaline hydrolysis and sonication) were tested to improve methane production and anaerobic biodegradability of different agro-food wastes and their mixtures. The kinetics of anaerobic degradation and methane production ofpre-treated individual wastes and selected mixtures were investigated with batch tests. Sonication at lower frequencies (37 kHz) proved to give the best results with methane productivity enhancements of over 100% in the case of pig manure and in the range of 10-47% for the other wastes assayed. Furthermore, the ultimate methane production was proportional, in all the cases, to the specific energy input applied (Es). Sonication can, thus, enhance waste digestion and the rate and quantity of biogas generated. The behaviour of the other pre-treatments under the conditions assayed is not significant. Only a slight enhancement of biogas production (around 10%) was detected for whey and waste activated sludge (WAS) after mechanical shredding. The lack of effectiveness of chemical pre-treatments (acid and alkaline hydrolysis) can be justified by the inhibition of the methanogenic process due to the presence of high concentrations of sodium (up to 8 g l(-1) in some tests). Only in the case of WAS did the acid hydrolysis considerably increase the biodegradability of the sample (79%), because in this case no inhibition by sodium took place. Some hints of a synergistic effect have been observed when co-digestion of the mixtures was performed. PMID:22988607

Hidalgo, D; Sastre, E; Gómez, M; Nieto, P



Increase in plasma phylloquinone concentrations following acupoint injection for the treatment of primary dysmenorrhea.  


The therapeutic benefits of acupoint injection of vitamin K in spleen-6 (SP6) for the treatment of primary dysmenorrhea have been observed in limited clinical settings. However, menadione, the form of vitamin K most studied for treating dysmenorrhea, is not routinely used in clinical practice in North America. As part of a larger clinical trial among women aged 18-25 years with primary dysmenorrhea, we conducted a substudy to test the plasma concentration of phylloquinone (vitamin K1). We collected blood samples from four women before and 24-48 hours after an acupoint injection of phylloquinone in SP6. Despite the rapid turnover of phylloquinone observed in previous studies, we found that the plasma phylloquinone concentrations increased significantly from preinjection to 1-2 days after the injection. Interestingly, higher phylloquinone concentrations were correlated with less pain intensity among women with dysmenorrhea. Additional research is needed to understand the association between vitamin K and menstrual pain, including the role of vitamin K deficiency in inflammation and pain, and on the possible mechanisms of acupoint injection of vitamin K for the treatment of primary dysmenorrhea. PMID:24929459

Chao, Maria T; Wade, Christine M; Booth, Sarah L



Permeability Enhancers Dramatically Increase Zanamivir Absolute Bioavailability in Rats: Implications for an Orally Bioavailable Influenza Treatment  

PubMed Central

We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS) permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol) was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (tmax of 5 min) and a Cmax of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted Cmax for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results are being utilized to design prototype dosage forms for initial human pharmacokinetic studies. PMID:23613954

Holmes, Eric H.; Devalapally, Harikrishna; Li, Libin; Perdue, Michael L.; Ostrander, Gary K.



Shortening treatment time in robotic radiosurgery using a novel node reduction technique  

SciTech Connect

Purpose: The fraction duration of robotic radiosurgery treatments can be reduced by generating more time-efficient treatment plans with a reduced number of node positions, beams, and monitor units (MUs). Node positions are preprogramed locations where the robot can position the focal spot of the x-ray beam. As the time needed for the robot to travel between node positions takes up a large part of the treatment time, the aim of this study was to develop and evaluate a node reduction technique in order to reduce the treatment time per fraction for robotic radiosurgery. Methods: Node reduction was integrated into the inverse planning algorithm, developed in-house for the robotic radiosurgery modality. It involved repeated inverse optimization, each iteration excluding low-contribution node positions from the planning and resampling new candidate beams from the remaining node positions. Node reduction was performed until the exclusion of a single node position caused a constraint violation, after which the shortest treatment plan was selected retrospectively. Treatment plans were generated with and without node reduction for two lung cases of different complexity, one oropharyngeal case and one prostate case. Plan quality was assessed using the number of node positions, beams and MUs, and the estimated treatment time per fraction. All treatment plans had to fulfill all clinical dose constraints. Extra constraints were added to maintain the low-dose conformality and restrict skin doses during node reduction. Results: Node reduction resulted in 12 residual node positions, on average (reduction by 77%), at the cost of an increase in the number of beams and total MUs of 28% and 9%, respectively. Overall fraction durations (excluding patient setup) were shortened by 25% (range of 18%-40%), on average. Dose distributions changed only little and dose in low-dose regions was effectively restricted by the additional constraints. Conclusions: The fraction duration of robotic radiosurgery treatments can be reduced considerably by node reduction with minimal changes in dosimetrical plan quality. Additional constraints are required to guarantee low-dose conformality and to avoid unacceptable skin dose.

Water, Steven van de; Hoogeman, Mischa S.; Breedveld, Sebastiaan; Heijmen, Ben J. M. [Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands)



Elevation of night-time temperature increases terpenoid emissions from Betula pendula and Populus tremula  

PubMed Central

Volatile organic compounds (VOCs) are expected to have an important role in plant adaptation to high temperatures. The impacts of increasing night-time temperature on daytime terpenoid emissions and related gene expression in silver birch (Betula pendula) and European aspen (Populus tremula) clones were studied. The plants were grown under five different night-time temperatures (6, 10, 14, 18, and 22?°C) while daytime temperature was kept at a constant 22?°C. VOC emissions were collected during the daytime and analysed by gas chromatography–mass spectrometry (GC-MS). In birch, emissions per leaf area of the C11 homoterpene 4,8-dimethy1-nona-1,3,7-triene (DMNT) and several sesquiterpenes were consistently increased with increasing night-time temperature. Total sesquiterpene (SQT) emissions showed an increase at higher temperatures. In aspen, emissions of DMNT and ?-ocimene increased from 6?°C to 14?°C, while several other monoterpenes and the SQTs (Z,E)-?-farnesene and (E,E)-?-farnesene increased up to 18?°C. Total monoterpene and sesquiterpene emission peaked at 18?°C, whereas isoprene emissions decreased at 22?°C. Leaf area increased across the temperature range of 6–22?°C by 32% in birch and by 59% in aspen. Specific leaf area (SLA) was also increased in both species. The genetic regulation of VOC emissions seems to be very complex, as indicated by several inverse relationships between emission profiles and expression of several regulatory genes (DXR, DXS, and IPP). The study indicates that increasing night temperature may strongly affect the quantity and quality of daytime VOC emissions of northern deciduous trees. PMID:20181662

Ibrahim, Mohamed A.; Mäenpää, Maarit; Hassinen, Viivi; Kontunen-Soppela, Sari; Malec, Lukáš; Rousi, Matti; Pietikäinen, Liisa; Tervahauta, Arja; Kärenlampi, Sirpa; Holopainen, Jarmo K.; Oksanen, Elina J.



Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease  

PubMed Central

In conjunction with the rise in rates of obesity, there has been an increase in the rate of nonalcoholic fatty liver disease (NAFLD). While NAFLD at least partially originates from poor diet, there is a lack of nutritional recommendations for patients with suspected or confirmed diagnosis of NAFLD, beyond eating a healthy diet, increasing physical activity, and emphasising weight loss. The limited current literature suggests that there may be opportunities to provide more tailored dietary advice for people diagnosed with or at risk of NAFLD. Epidemiological studies consistently find associations between whole grain intake and a reduced risk of obesity and related diseases, yet no work has been done on the potential of whole grains to prevent and/or be a part of the treatment for fatty liver diseases. In this review, we examine the potential and the current evidence for whole grains having an impact on NAFLD. Due to their nutrient and phytochemical composition, switching from consuming mainly refined grains to whole grains should be considered as part of the nutritional guidelines for patients diagnosed with or at risk for fatty liver disease. PMID:23762052

Ross, Alastair B.; Godin, Jean-Philippe; Minehira, Kaori; Kirwan, John P.



Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal  

PubMed Central

Introduction Current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, there is a clear need to develop novel antismoking medications. Nicotine withdrawal is associated with cognitive impairments that predict smoking relapse. It has been proposed that these cognitive deficits are a hallmark of nicotine withdrawal that could be targeted in order to prevent smoking relapse. Thus, pharmacotherapies that increase cognitive performance during nicotine withdrawal may represent potential smoking cessation agents. Areas covered The authors review the clinical literature demonstrating that nicotine withdrawal is associated with deficits in working memory, attention and response inhibition. They then briefly summarize different classes of compounds and strategies to increase cognitive performance during nicotine withdrawal. Particular emphasis has been placed on translational research in order to highlight areas for which there is strong rationale for pilot clinical trials of potential smoking cessation medications. Expert opinion There is emerging evidence that supports deficits in cognitive function as a plausible nicotine withdrawal phenotype. The authors furthermore believe that the translational paradigms presented here may represent efficient and valid means for the evaluation of cognitive-enhancing medications as possible treatments for nicotine dependence. PMID:24707983

Ashare, Rebecca L; Schmidt, Heath D



Surgical Operative Time Increases the Risk of Deep Venous Thrombosis and Pulmonary Embolism in Robotic Prostatectomy  

PubMed Central

Background and Objectives: To evaluate the effect of operative time on the risk of symptomatic venous thromboembolic events (VTEs) in patients undergoing robot-assisted radical prostatectomy (RARP). Methods: We reviewed the records of all patients at our institution who underwent RARP by a single surgeon from January 2007 until April 2011. Clinical and pathologic information and VTE incidence were recorded for each patient and analyzed by use of logistic regression to evaluate for association with VTE risk. All patients had mechanical prophylaxis, and beginning in February 2008, a single dose of unfractionated heparin, 5000 U, was administered before surgery. Results: A total of 549 consecutive patients were identified, with a median follow-up period of 8 months. During the initial 30 days postoperatively, 10 patients (1.8%) had a VTE (deep venous thrombosis in 7 and pulmonary embolism in 3). The median operative time was 177 minutes (range, 121–360 minutes). An increase in operative time of 30 or 60 minutes was associated with 1.6 and 2.8 times increased VTE risks. A 5-point increase in body mass index and need for blood transfusion were also associated with increased risk of VTEs (odds ratios of 2.0 and 11.8, respectively). Heparin prophylaxis was not associated with a significant VTE risk reduction but also was not associated with a significant increase in estimated blood loss (P = .23) or transfusion rate (P = .37). Conclusion: A prolonged operative time increases the risk of symptomatic VTEs after RARP. Future studies are needed to evaluate the best VTE prophylactic approach in patients at risk. PMID:24960494

Wong, Kelvin; Sado, Martins; Leverson, Glen E.; Patel, Sutchin R.; Downs, Tracy M.; Jarrard, David F.



Increase in tumour permeability following TGF-? type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI  

PubMed Central

Background: To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent. Methods: To apply transforming growth factor (TGF)-? type I receptor (T?R-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium (Gd)-DTPA and for its liposomal formulation to evaluate changes in tumour microvasculature following A-83-01. Tumour vascular parameters from DCE-MRI were compared with histological assessment and apparent diffusion coefficient of water in tumour generated by diffusion-weighted MRI. Results: Contrary to evaluations reported for anti-angiogenic agents, A-83-01 treatment increased the initial area under the Gd concentration–time curve (IAUGC60), volume transfer constant (Ktrans) and fractional plasma volume (vp) significantly within 24?h, that was positively related to ?-smooth muscle actin-positive pericyte coverage and tumour cell proliferation, and was correlated inversely with the apparent diffusion coefficient. The vascular function of the tumour improved by A-83-01 treatment was well assessed on post-liposomal Gd-DTPA-enhanced MR images, which predicted delivery of a liposomal drug to the tumour. Conclusion: These findings suggest that DCE-MRI and, in particular, Ktrans and vp quantitation, provide important additional information about tumour vasculature by A-83-01 treatment. PMID:19888220

Minowa, T; Kawano, K; Kuribayashi, H; Shiraishi, K; Sugino, T; Hattori, Y; Yokoyama, M; Maitani, Y



Organizing "Play Streets" during school vacations can increase physical activity and decrease sedentary time in children.  


A Play Street is a street that is reserved for children's safe play for a specific period during school vacations. It was hypothesized that a Play Street near children's home can increase their moderate- to vigorous-intensity physical activity (MVPA) and decrease their sedentary time. Therefore, the aim of this study was to investigate the effect of Play Streets on children's MVPA and sedentary time.A nonequivalent control group pretest-posttest design was used to determine the effects of Play Streets on children's MVPA and sedentary time. Data were collected in Ghent during July and August 2013. The study sample consisted of 126 children (54 from Play streets, 72 from control streets). Children wore an accelerometer for 8 consecutive days and their parents fill out a questionnaire before and after the measurement period. During the intervention, streets were enclosed and reserved for children's play. Four-level (neighborhood - household - child - time of measurement (no intervention or during intervention)) linear regression models were conducted in MLwiN to determine intervention effects.Positive intervention effects were found for sedentary time (??=?-0.76?±?0.39; ?(2)?=?3.9; p?=?0.05) and MVPA (??=?0.82?±?0.43; ?(2)?=?3.6; p?=?0.06). Between 14h00 and 19h00, MVPA from children living in Play Streets increased from 27 minutes during normal conditions to 36 minutes during the Play Street intervention, whereas control children's MVPA decreased from 27 to 24 minutes. Sedentary time from children living in the Play Street decreased from 146 minutes during normal conditions to 138 minutes during the Play Street intervention, whereas control children's sedentary time increased from 156 minutes to 165 minutes. The intervention effects on MVPA (??=?-0.62?±?0.25; ?(2)?=?6.3; p?=?0.01) and sedentary time (??=?0.85?±?0.0.33; ?(2)?=?6.6; p?=?0.01) remained significant when the effects were investigated during the entire day, indicating that children did not compensate for their increased MVPA and decreased sedentary time, during the rest of the day.Creating a safe play space near urban children's home by the Play Street intervention is effective in increasing children's MVPA and decreasing their sedentary time. PMID:25778957

D'Haese, Sara; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Cardon, Greet



Increased incidence of another cancer in myeloproliferative neoplasms patients at the time of diagnosis.  


Several studies have reported an increased incidence of coexistent cancer in patients with myeloproliferative neoplasms (MPN), and myelosuppressive treatment has been speculated to be one of the causes. In this study, we have concentrated on malignancies diagnosed before the MPN diagnosis to eliminate the possible influence of MPN treatment. The patients were recruited from the Swedish and Norwegian cancer registries. One thousand seven hundred and 45 patients from the Swedish MPN Quality Registry and 468 patients from the Norwegian National Cancer Registry were included in this study covering a 3-yr period. The results show that primary concurrent cancer is higher among patients with MPN compared to the general population. When pooled together, the Swedish and the Norwegian cohort showed increased prevalence of all types of cancer in general compared with the general population, standard prevalence ratio (SPR) of 1.20 (95% CI 1.07-1.34). Significantly high SPRs were reached for skin malignant melanoma [1.89 (95% CI 1.33-2.62)], prostate cancer [1.39 (95% CI 1.11-1.71)], and hematologic cancer [1.49 (95% CI 1.00-2.12)]. In the polycythemia vera group, the risk of having prior malignant melanoma of the skin was significant, with an SPR of 2.20 (95% CI 1.17-3.77). For patients with essential thrombocythemia and primary myelofibrosis, no significant risks were found. Coexisting cancers have a high impact on the treatment strategies of MPN, as it narrows down the treatment options. Chronic inflammation, as a common denominator of MPN with other cancers, can catalyze each other's existence and progression. PMID:25039361

Pettersson, Helna; Knutsen, Håvar; Holmberg, Erik; Andréasson, Björn



Improving Reading Achievement Through Increased Motivation, Specific Skill Enhancement, and Practice Time for Elementary Students  

ERIC Educational Resources Information Center

The action research project report began when the teacher researchers determined that students at Sites A and B struggled with reading achievement. The purpose of the project was to improve students' reading achievement through increased motivation, specific skill instruction, and additional practice time. The project involved 26 students: 17…

Ecklund, Britt K.; Lamon, Kathryn M.



Federal Rule Yields Hope for Science: Testing Mandate Is Expected to Increase Time for Subject  

ERIC Educational Resources Information Center

Some proponents of science education say they have faced no greater foe over the past few years than federally mandated tests in reading and mathematics, which have forced teachers to devote increasingly bigger chunks of class time to building students' skills in those two subjects. But if testing has squeezed science out, can testing also bring…

Cavanagh, Sean



Improving Student Attitudes and Writing Abilities through Increased Writing Time and Opportunities.  

ERIC Educational Resources Information Center

This report describes a program for improving student abilities and attitudes toward writing through increased writing time and opportunities. The targeted population consists of second, third, fourth, and fifth grade students at the elementary level in a growing middle class community located in the northwest suburban area of Chicago, Illinois.…

Gau, Elisabeth; Hermanson, Jennifer; Logar, Michele; Smerek, Christine


Static Fatigue, Time Effects, and Delayed Increase in Penetration Resistance after  

E-print Network

Static Fatigue, Time Effects, and Delayed Increase in Penetration Resistance after Dynamic for the latter is found in the micromechanics process of static fatigue (or stress corrosion cracking stress under one-dimensional strain conditions. This process is a consequence of static fatigue

Michalowski, Radoslaw L.


Sequential Treatment with Basic Fibroblast Growth Factor and PTH Is More Efficacious than Treatment with PTH Alone for Increasing Vertebral Bone Mass and Strength in Osteopenic Ovariectomized Rats  

Microsoft Academic Search

The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microar- chitecture in osteopenic ovariectomized rats, and 2) to assess whether prior and concurrent administration of the antire- sorptive agents estrogen and risedronate suppresses the bone




Increasing temperature forcing reduces the Greenland Ice Sheet's response time scale  

NASA Astrophysics Data System (ADS)

Damages from sea level rise, as well as strategies to manage the associated risk, hinge critically on the time scale and eventual magnitude of sea level rise. Satellite observations and paleo-data suggest that the Greenland Ice Sheet (GIS) loses mass in response to increased temperatures, and may thus contribute substantially to sea level rise as anthropogenic climate change progresses. The time scale of GIS mass loss and sea level rise are deeply uncertain, and are often assumed to be constant. However, previous ice sheet modeling studies have shown that the time scale of GIS response likely decreases strongly with increasing temperature anomaly. Here, we map the relationship between temperature anomaly and the time scale of GIS response, by perturbing a calibrated, three-dimensional model of GIS behavior. Additional simulations with a profile, higher-order, ice sheet model yield time scales that are broadly consistent with those obtained using the three-dimensional model, and shed light on the feedbacks in the ice sheet system that cause the time scale shortening. Semi-empirical modeling studies that assume a constant time scale of sea level adjustment, and are calibrated to small preanthropogenic temperature and sea level changes, may underestimate future sea level rise. Our analysis suggests that the benefits of reducing greenhouse gas emissions, in terms of avoided sea level rise from the GIS, may be greatest if emissions reductions begin before large temperature increases have been realized. Reducing anthropogenic climate change may also allow more time for design and deployment of risk management strategies by slowing sea level contributions from the GIS.

Applegate, Patrick J.; Parizek, Byron R.; Nicholas, Robert E.; Alley, Richard B.; Keller, Klaus



DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from db/db mice {beta} cells  

SciTech Connect

Highlights: {yields} Anti-diabetic new drug, DPP-4 inhibitor, can affect the insulin exocytosis. {yields} DPP-4 inhibitor treatment altered syntaxin 1 expression. {yields} Treatment of db/db mice with DPP-4 inhibitor increased insulin release. -- Abstract: Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4 inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used as therapeutics for type 2 diabetes. However, the effects of sitagliptin-treatment on insulin exocytosis from single {beta}-cells are yet unknown. We therefore investigated how sitagliptin-treatment in db/db mice affects insulin exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion. We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF imaging system. TIRF imaging of insulin exocytosis showed the increased number of docked insulin granules and increased fusion events from them during first-phase release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion events of insulin granules, probably via increased number of docked insulin granules and that of syntaxin 1 clusters.

Nagamatsu, Shinya, E-mail: [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan)] [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan); Ohara-Imaizumi, Mica; Nakamichi, Yoko; Aoyagi, Kyota; Nishiwaki, Chiyono [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan)] [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan)



Pluronic modified leptin with increased systemic circulation, brain uptake and efficacy for treatment of obesity.  


Modification of hydrophilic proteins with amphiphilic block copolymers capable of crossing cell membranes is a new strategy to improve protein delivery to the brain. Leptin, a candidate for the treatment of epidemic obesity, has failed in part because of impairment in its transport across the blood-brain barrier (BBB) that develops with obesity. We posit that modification of leptin with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Pluronic P85 (P85) might permit this protein to penetrate the BBB independently of its transporter, thereby overcoming peripheral leptin resistance. Here we report that peripherally administered leptin-P85 conjugates exhibit biological activity by reducing food intake in mouse models of obesity (ob/ob, and diet-induced obese mouse). We further generated two new leptin-P85 conjugates: one, Lep(ss)-P85(L), containing one P85 chain and another, Lep(ss)-P85(H), containing multiple P85 chains. We report data on their purification, analytical characterization, peripheral and brain pharmacokinetics (PK). Lep(ss)-P85(L) crosses the BBB using the leptin transporter, and exhibits improved peripheral PK along with increased accumulation in the brain compared to unmodified leptin. Lep(ss)-P85(H) also has improved peripheral PK but in a striking difference to the first conjugate penetrates the BBB independently of the leptin transporter via a non-saturable mechanism. The results demonstrate that leptin analogs can be developed through chemical modification of the native leptin with P85 to overcome leptin resistance at the level of the BBB, thus improving the potential for the treatment of obesity. PMID:24881856

Yi, Xiang; Yuan, Dongfen; Farr, Susan A; Banks, William A; Poon, Chi-Duen; Kabanov, Alexander V



Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia  

PubMed Central

Background Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations The main limitation of this study is its cross-sectional design. Conclusion To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. PMID:25268790

Schirmbeck, Frederike; Mier, Daniela; Esslinger, Christine; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias



Implementation of a patient selection protocol for intra-arterial therapy increases treatment rates in patients with acute ischemic stroke  

PubMed Central

Background Strategies for patient selection for intra-arterial therapy (IAT) in acute ischemic stroke (AIS) are highly variable. The degree of protocol adoption and treatment rates associated with implementation of a service-wide patient selection IAT protocol were assessed. Methods All patients with AIS prospectively recorded in our stroke database from January 2007 to June 2009 were reviewed. The IAT patient selection protocol was implemented in March 2008. Patients were defined as likely to benefit (LTB) from IAT if they had brain imaging completed within 6 h from last known well time, NIH Stroke Scale score ?8, infarct volume ?100 ml and evidence of proximal artery occlusion. Results Of 1348 subjects identified, 118 (8.7%) met the criteria for LTB and 62 (52%) underwent IAT. There was a significant increase in rates of IAT among LTB patients after protocol implementation (61% vs 40%, p<0.02). In LTB patients, factors associated with IAT were stroke duration (OR 0.78, 95% CI 0.6 to 0.9 per hour), arrival within later calendar months during study period (OR 1.1, 95% CI 1.02 to 1.2 per month), intravenous tissue plasminogen activator (OR 0.6, 95% CI 0.4 to 0.9) and age (OR 0.98, 95% CI 0.95 to 1.02 per year). After multivariable adjustment, only stroke duration (OR 0.65, 95% CI 0.5 to 0.8 per hour) remained an independent predictor of IAT. Conclusions Most patients with AIS did not meet our criteria for LTB and only 52% of those defined as LTB received IAT. Protocol adoption increased the use of IAT over time; however, further exploration of factors associated with the reasons for non-treatment and the impact of IAT on outcomes is necessary. PMID:22611045

Rost, Natalia S; Smith, Eric E; Nogueira, Raul G; Fitzpatrick, Kaitlin M; Yoo, Albert J; Hirsch, Joshua A; Schwamm, Lee H



Robust discretizations versus increase of the time step for the Lorenz system  

NASA Astrophysics Data System (ADS)

When continuous systems are discretized, their solutions depend on the time step chosen a priori. Such solutions are not necessarily spurious in the sense that they can still correspond to a solution of the differential equations but with a displacement in the parameter space. Consequently, it is of great interest to obtain discrete equations which are robust even when the discretization time step is large. In this paper, different discretizations of the Lorenz system are discussed versus the values of the discretization time step. It is shown that the sets of difference equations proposed are more robust versus increases of the time step than conventional discretizations built with standard schemes such as the forward Euler, backward Euler, or centered finite difference schemes. The nonstandard schemes used here are Mickens' scheme and Monaco and Normand-Cyrot's scheme.

Letellier, Christophe; Mendes, Eduardo M. A. M.



Analysis of an Anomaly: The Increase in Time Float following Consumption  

PubMed Central

One fundamental axiom for project plan and schedule relates to the notion that time float will be reduced following its consumption. However, an anomalous scenario can emerge in which an activity's time float increases following its consumption. By exploring the associations between time float and paths in activity networks, we (a) reveal the conditions under which the anomaly occurs and (b) summarize laws related to total float. An activity's total float increases in parallel with its duration prolongation within a given boundary but remains constant or decreases in parallel with a prolongation outside the boundary. Furthermore, whereas a prolongation of an activity's duration in excess of classic total float does not delay project completion time, a lag of its start time to a degree slightly greater than the total float does. This analysis reveals different types of total float that correspond to different ways of usage. From this, we offer definitions for translation total float and prolongation total float that deviate from traditional conventions regarding the uniqueness of total float. PMID:25250376

Qi, Jianxun; Su, Zhixiong



Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer  

SciTech Connect

Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived {>=} 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

Wang Li [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI (United States); Department of Radiation Oncology, Cancer Center, Fudan University, Shanghai (China); Correa, Candace R.; Hayman, James A.; Zhao Lujun [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI (United States); Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P. [Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI (United States); Kong, F.-M. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI (United States); Department of Radiation Oncology, Veterans Administration Health Center, Ann Arbor, MI (United States)], E-mail:



Treatment of PC12 cells with nerve growth factor increases iron uptake.  

PubMed Central

Phaeochromocytoma PC12 cells treated with nerve growth factor (NGF) differentiate into a neuronal phenotype. Here we compare the uptake of transferrin-bound and non-transferrin-bound iron in NGF-treated (neuronal phenotype) and control (proliferating) PC12 cells. The non-transferrin-bound iron uptake was greater in the NGF-treated cells than in the control, independently of the uptake time, the iron-chelating agents used, the oxidation state of iron (Fe(2+) or Fe(3+)) and the iron concentration tested. The NGF-treated cells expressed L-type and N-type voltage-operated Ca(2+) channels. Nitrendipine (an L-type inhibitor) and possibly omega-conotoxin (an N-type inhibitor) inhibited the iron uptake by 20%. Thapsigargin inhibits the endoplasmic reticulum Ca(2+) pump and allowed Mn(2+) entry into cells. Preincubating PC12 cells with thapsigargin increased the iron uptake. The rate of transferrin-bound iron uptake was less than 1% of the non-transferrin-bound iron uptake and the maximum transferrin-bound iron uptake was also very low. We conclude that an increase in the iron uptake by multiple pathways accompanies the transition of PC12 cells from the proliferating to the neuronal phenotype. PMID:11463361

Mwanjewe, J; Hui, B K; Coughlin, M D; Grover, A K



Visualisation of blood and lymphatic vessels with increasing exposure time of the detector  

NASA Astrophysics Data System (ADS)

We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions.

Kalchenko, V. V.; Kuznetsov, Yu L.; Meglinski, I. V.



Visualisation of blood and lymphatic vessels with increasing exposure time of the detector  

SciTech Connect

We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions. (laser applications in biology and medicine)

Kalchenko, V V; Kuznetsov, Yu L; Meglinski, I V



Effect of increased noise levels by supersonic aircraft on annoyance levels and time estimations.  


Several tests designed to assess the effects of increased noise levels created by the Concorde supersonic aircraft were administered to 48 residents living around Dulles International Airport and 31 persons not living near an airport. Results of a pretest questionnaire and lack of significant changes in annoyance levels and time estimations indicate that, while airport-area residents may be more conscious of aircraft noise, changes in the perceived intensities of sounds may not occur. PMID:7375309

Allen, J A



Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules  

E-print Network

Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules Samuel the best timing of treatments. However, the influence of variations in tumor kinetics has not been kinetics of the tumor. Then, we developed a theoretical analysis of treatment outcome (TATO) to relate

Paris-Sud XI, Université de


The Timing of Exposure in Clinic-Based Treatment for Childhood Anxiety Disorders  

ERIC Educational Resources Information Center

The present study examines treatment length and timing of exposure from two child anxiety disorders clinics. Data regarding symptoms and treatment characteristics for 28 youth were prospectively obtained through self, parent, and therapist report at each session. Information regarding length of treatment, timing of exposure initiation, and…

Gryczkowski, Michelle R.; Tiede, Michael S.; Dammann, Julie E.; Jacobsen, Amy Brown; Hale, Lisa R.; Whiteside, Stephen P. H.



The effects of time and money prices on treatment attendance for methadone maintenance clients.  


Many methadone maintenance clients are required to visit a clinic daily, so treatment attendance is essential for clients' compliance and treatment effectiveness. Using data derived from a unique survey, this study provides evidence of economic barriers to regular treatment attendance. Hypotheses tested are (1) higher personal costs reduce treatment attendance, and (2) willingness to pay (WTP) provides better time price estimates than wage rates. The findings suggest that both time and money function as rationing devices for methadone maintenance clients. The study finds WTP preferable to wage rate in measuring time price as evaluated by the effects of time price on treatment attendance. PMID:14698798

Borisova, Natalia N; Goodman, Allen C



Increased physical activity not decreased energy intake is associated with inpatient medical treatment for anorexia nervosa in adolescent females.  


There is a dearth of data regarding changes in dietary intake and physical activity over time that lead to inpatient medical treatment for anorexia nervosa (AN). Without such data, more effective nutritional therapies for patients cannot be devised. This study was undertaken to describe changes in diet and physical activity that precede inpatient medical hospitalization for AN in female adolescents. This data can be used to understand factors contributing to medical instability in AN, and may advance rodent models of AN to investigate novel weight restoration strategies. It was hypothesized that hospitalization for AN would be associated with progressive energy restriction and increased physical activity over time. 20 females, 11-19 years (14.3±1.8 years), with restricting type AN, completed retrospective, self-report questionnaires to assess dietary intake and physical activity over the 6 month period prior to inpatient admission (food frequency questionnaire, Pediatric physical activity recall) and 1 week prior (24 hour food recall, modifiable activity questionnaire). Physical activity increased acutely prior to inpatient admission without any change in energy or macronutrient intake. However, there were significant changes in reported micronutrient intake causing inadequate intake of Vitamin A, Vitamin D, and pantothenic acid at 1 week versus high, potentially harmful, intake of Vitamin A over 6 months prior to admission. Subject report of significantly increased physical activity, not decreased energy intake, were associated with medical hospitalization for AN. Physical activity and Vitamin A and D intake should be carefully monitored following initial AN diagnosis, as markers of disease progression as to potentially minimize the risk of medical instability. PMID:23637854

Higgins, Janine; Hagman, Jennifer; Pan, Zhaoxing; MacLean, Paul



Causal Effects of Time-Dependent Treatments in Older Patients with Non-Small Cell Lung Cancer  

PubMed Central

Background Treatment selection for elderly patients with lung cancer must balance the benefits of curative/life-prolonging therapy and the risks of increased mortality due to comorbidities. Lung cancer trials generally exclude patients with comorbidities and current treatment guidelines do not specifically consider comorbidities, so treatment decisions are usually made on subjective individual-case basis. Methods Impacts of surgery, radiation, and chemotherapy mono-treatment as well as combined chemo/radiation on one-year overall survival (compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o. patients. Methods of causal inference such as propensity score with inverse probability weighting (IPW) for time-independent and marginal structural model (MSM) for time-dependent treatments are applied to SEER-Medicare data considering the presence of comorbid diseases. Results 122,822 patients with stage I (26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were selected. Younger age, smaller tumor size, and fewer baseline comorbidities predict better survival. Impacts of radio- and chemotherapy increased and impact of surgery decreased with more advanced cancer stages. The effects of all therapies became weaker after adjustment for selection bias, however, the changes in the effects were minor likely due to the weak selection bias or incompleteness of the list of predictors that impacted treatment choice. MSM provides more realistic estimates of treatment effects than the IPW approach for time-independent treatment. Conclusions Causal inference methods provide substantive results on treatment choice and survival of older lung cancer patients with realistic expectations of potential benefits of specific treatments. Applications of these models to specific subsets of patients can aid in the development of practical guidelines that help optimize lung cancer treatment based on individual patient characteristics. PMID:25849715

Akushevich, Igor; Arbeev, Konstantin; Kravchenko, Julia; Berry, Mark




PubMed Central

BACKGROUND Culturally competent practice is broadly acknowledged to be an important strategy to increase the quality of services for racial/ethnic minorities in substance abuse treatment. However, few empirically derived measures of organizational cultural competence exist, and relatively little is known about how these measures affect treatment outcomes. METHOD Using a nationally representative sample of outpatient substance abuse treatment (OSAT) programs, this study used item response theory to create two measures of cultural competence-organizational practices and managers' culturally sensitive beliefs—and examined their relationship to client wait time and retention using Poisson regression modeling RESULTS The most common and precisely measured organizational practices reported by OSAT managers included matching providers and clients based on language/dialect; offering cross-cultural training; and fostering connections with community and faith-based organizations connected to racial and ethnic minority groups. The most culturally sensitive belief among OSAT managers was support for language/dialect matching for racial and ethnic minority clients. Results of regression modeling indicate that organizational practices were not related to either outcome. However, managers' culturally sensitive beliefs were negatively associated with average wait time (p < 0.05), and positively associated with average retention (p < 0.01). CONCLUSIONS Managers' culturally sensitive beliefs—considered to be influential for effective implementation of culturally competent practices—may be particularly relevant in influencing wait time and retention in OSAT organizations that treat Latinos and African American clients. PMID:21680111

Guerrero, Erick; Andrews, Christina M.



Effect of a 15% increase in preferred pedal rate on time to exhaustion during heavy exercise.  


The aim of this study was to evaluate the effect of a 15% increase in preferred pedal rate (PPR) on both time to exhaustion and pulmonary O(2) uptake (VO(2)) response during heavy exercise. Seven competitive cyclists underwent two constant-power tests (CPT) at a power output that theoretically requires 50% of the difference in VO(2) between the second ventilatory threshold and VO(2)max (Pdelta50). Each cyclist cycled a CPT at PPR (CPTPPR) and a CPT at +15% of PPR (CPT+15%) in a randomized order. The average PPR value was 94 +/- 4 rpm, and time to exhaustion was significantly longer in CPTPPR compared with CPT+15% (465 +/- 139 vs. 303+/- 42 s, respectively; p = 0.01). A significant decrease in VO(2) values in the first minutes of exercise and a significant increase in VO(2) slow component was reported in CPT+15% compared with CPT(PPR). These data indicate that the increase of 15% PPR was associated with a decrease in exercise tolerance and a specific VO(2) response, presumably due to an increase of negative muscular work, internal work, and an altering of motor unit recruitment patterns. PMID:15064424

Nesi, Xavier; Bosquet, Laurent; Berthoin, Serge; Dekerle, Jeanne; Pelayo, Patrick



Treatment for Partner Abuse: Time for a Paradigm Shift  

Microsoft Academic Search

The standard approach of arresting abusers and mandating their participation in short-term group treatment produces mixed results at best. Six problematic assumptions compromise the outcome of this 1-size-fits-all intervention. A review of these assumptions suggests the need for a paradigmatic shift toward the need to identify abusers who can and cannot be helped. For those amenable to treatment, intervention should

Richard B. Stuart



Histone Deacetylase Inhibitor Treatment Increases Coronary t-PA Release in a Porcine Ischemia Model  

PubMed Central

Background The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control. Objectives The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity. Methods In an anaesthetized pig model, a controlled transient coronary occlusion was used to stimulate coronary tissue plasminogen activator release in a valproic acid treated (one week) and a non-treated group. Coronary venous blood samples from the ischemic region were collected, great cardiac vein thermodilution flow measurements were performed, and trans-coronary tissue plasminogen activator fluxes were calculated. Plasminogen activator inhibitor-1 was also measured. Results Adequate sampling from the affected area after the 10 minute ischemic period was confirmed by lactate measurements. Fluxes for tissue plasminogen activator at minutes 1, 3, 5, 7 and 10 were measured and then used to present cumulative net tissue plasminogen activator release for the whole measurement period for both groups. Area under the curve was higher for the valproic acid treated group at 10 minutes; 932±173 nanograms (n?=?12) compared to the non-treated group, 451±78 nanograms (n?=?10, p?=?0.023). There was no difference in levels of plasminogen activator inhibitor-1 between groups. Conclusions These findings support a proof of concept for histone deacetylation inhibition positive effect on tissue plasminogen activator expression in an in vivo setting. Further studies are needed to find an optimal way to implement histone deacetylation inhibition to achieve desired clinical changes in tissue plasminogen activator expression. PMID:24818610

Svennerholm, Kristina; Bergh, Niklas; Larsson, Pia; Jern, Sverker; Johansson, Göran; Biber, Björn; Haney, Michael



Ambush frequency should increase over time during optimal predator search for prey.  


We advance and apply the mathematical theory of search games to model the problem faced by a predator searching for prey. Two search modes are available: ambush and cruising search. Some species can adopt either mode, with their choice at a given time traditionally explained in terms of varying habitat and physiological conditions. We present an additional explanation of the observed predator alternation between these search modes, which is based on the dynamical nature of the search game they are playing: the possibility of ambush decreases the propensity of the prey to frequently change locations and thereby renders it more susceptible to the systematic cruising search portion of the strategy. This heuristic explanation is supported by showing that in a new idealized search game where the predator is allowed to ambush or search at any time, and the prey can change locations at intermittent times, optimal predator play requires an alternation (or mixture) over time of ambush and cruise search. Thus, our game is an extension of the well-studied 'Princess and Monster' search game. Search games are zero sum games, where the pay-off is the capture time and neither the Searcher nor the Hider knows the location of the other. We are able to determine the optimal mixture of the search modes when the predator uses a mixture which is constant over time, and also to determine how the mode mixture changes over time when dynamic strategies are allowed (the ambush probability increases over time). In particular, we establish the 'square root law of search predation': the optimal proportion of active search equals the square root of the fraction of the region that has not yet been explored. PMID:21571944

Alpern, Steve; Fokkink, Robbert; Timmer, Marco; Casas, Jérôme



Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy.  


The purposes of the study reported here were to evaluate the signalment and clinical presentation in 50 dogs with degenerative myelopathy, to evaluate whether mean survival time was significantly affected by various means of physiotherapy performed in 22 dogs, and to determine whether neurologic status, anatomic localization, or age at onset had an influence on survival time in dogs that received physiotherapy. We found a significant (P < .05) breed predisposition for the German Shepherd Dog, Kuvasz, Hovawart, and Bernese Mountain Dog. Mean age at diagnosis was 9.1 years, and both sexes were affected equally. The anatomic localization of the lesion was spinal cord segment T3-L3 in 56% (n = 28) and L3-S3 in 44% (n = 22) of the dogs. Animals that received intensive (n = 9) physiotherapy had longer (P < .05) survival time (mean 255 days), compared with that for animals with moderate (n = 6; mean 130 days) or no (n = 7; mean 55 days) physiotherapy. In addition, our results indicate that affected dogs which received physiotherapy remained ambulatory longer than did animals that did not receive physical treatment. PMID:16955818

Kathmann, I; Cizinauskas, S; Doherr, M G; Steffen, F; Jaggy, A



Socio-cultural determinants of timely and delayed treatment of Buruli ulcer: Implications for disease control  

PubMed Central

Introduction Public health programmes recommend timely medical treatment for Buruli ulcer (BU) infection to prevent pre-ulcer conditions from progressing to ulcers, to minimise surgery, disabilities and the socio-economic impact of BU. Clarifying the role of socio-cultural determinants of timely medical treatment may assist in guiding public health programmes to improve treatment outcomes. This study clarified the role of socio-cultural determinants and health system factors affecting timely medical treatment for BU in an endemic area in Ghana. Methods A semi-structured explanatory model interview based on the explanatory model interview catalogue (EMIC) was administered to 178 BU-affected persons. Based on research evidence, respondents were classified as timely treatment (use of medical treatment 3 months from awareness of disease) and delayed treatment (medical treatment 3 months after onset of disease and failure to use medical treatment). The outcome variable, timely treatment was analysed with cultural epidemiological variables for categories of distress, perceived causes of BU, outside-help and reasons for medical treatment in logistic regression models. The median time for the onset of symptoms to treatment was computed in days. Qualitative phenomenological analysis of respondents’ narratives clarified the meaning, context and dynamic features of the relationship of explanatory variables with timely medical treatment. Results The median time for initiating treatment was 25 days for pre-ulcers, and 204 days for ulcers. Income loss and use of herbalists showed significantly negative associations with timely treatment. Respondents’ use of herbalists was often motivated by the desire for quick recovery in order to continue with work and because herbalists were relatives and easily accessible. However, drinking unclean water was significantly associated with timely treatment and access to health services encouraged timely treatment (OR 8.5, p?=?0.012). Findings show that health system factors of access are responsible for non-compliance to treatment regimes. Conclusions Findings highlight the importance of an integrated approach to BU control and management considering the social and economic features that influence delayed treatment and factors that encourage timely medical treatment. This approach should consider periodic screening for early case-detection, collaboration with private practitioners and traditional healers, use of mobile services to improve access, adherence and treatment outcomes. PMID:23849228



Influence of plasma treatment time on plasma induced vapor phase grafting modification of PBO fiber surface  

NASA Astrophysics Data System (ADS)

The surface of poly-p-phenylene benzobisthiazole (PBO) fibers was treated through oxygen plasma induced vapor phase grafting (PIVPG) method under various oxygen plasma pre-treatment time conditions. The surface chemical composition, surface morphologies and surface free energy of pristine and treated PBO fibers were studied using X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and Cahn DCAA system. The mechanics property of these fibers was evaluated by tensile strength and interfacial shear strength (IFSS). It was found that the surface characteristics of treated PBO fibers occurred significant change compare with the pristine PBO fibers. After treatment, the polar functional groups were introduced on the fiber surface. Carbon concentration decreased; oxygen concentration and elemental ratio of oxygen to carbon increased. Acrylic acid can react with the activated PBO fibers surface, which led to the fiber surface roughness increased. The surface free energy increased from 41.4 mN/m to 62.8 mN/m when PBO fibers were plasma pre-treated for 10 min, while the IFSS of PBO fibers with epoxy resin increased from 36.6 MPa to 55.8 MPa. Therefore, PIVPG can be used to enhance the interfacial bond between PBO fibers and epoxy resin.

Song, B.; Meng, L. H.; Huang, Y. D.



An advection-based model to increase the temporal resolution of PIV time series  

NASA Astrophysics Data System (ADS)

A numerical implementation of the advection equation is proposed to increase the temporal resolution of PIV time series. The method is based on the principle that velocity fluctuations are transported passively, similar to Taylor's hypothesis of frozen turbulence. In the present work, the advection model is extended to unsteady three-dimensional flows. The main objective of the method is that of lowering the requirement on the PIV repetition rate from the Eulerian frequency toward the Lagrangian one. The local trajectory of the fluid parcel is obtained by forward projection of the instantaneous velocity at the preceding time instant and backward projection from the subsequent time step. The trajectories are approximated by the instantaneous streamlines, which yields accurate results when the amplitude of velocity fluctuations is small with respect to the convective motion. The verification is performed with two experiments conducted at temporal resolutions significantly higher than that dictated by Nyquist criterion. The flow past the trailing edge of a NACA0012 airfoil closely approximates frozen turbulence, where the largest ratio between the Lagrangian and Eulerian temporal scales is expected. An order of magnitude reduction of the needed acquisition frequency is demonstrated by the velocity spectra of super-sampled series. The application to three-dimensional data is made with time-resolved tomographic PIV measurements of a transitional jet. Here, the 3D advection equation is implemented to estimate the fluid trajectories. The reduction in the minimum sampling rate by the use of super-sampling in this case is less, due to the fact that vortices occurring in the jet shear layer are not well approximated by sole advection at large time separation. Both cases reveal that the current requirements for time-resolved PIV experiments can be revised when information is poured from space to time. An additional favorable effect is observed by the analysis in the frequency domain whereby the spectrum becomes significantly less prone to aliasing error for the super-sampled data series.

Scarano, Fulvio; Moore, Peter



A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification  

SciTech Connect

Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

Mourad, Waleed F., E-mail: [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Department of Radiation Oncology, Beth Israel Medical Center, New York, NY (Israel); Packianathan, Satyaseelan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Shourbaji, Rania A. [Department of Epidemiology and Biostatistics, Jackson State University, Jackson, MS (United States); Zhang Zhen; Graves, Mathew [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Khan, Majid A. [Department of Radiology, University of Mississippi Medical Center, Jackson, MS (United States); Baird, Michael C. [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Russell, George [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States)



Shear Stress Increases the Residence Time of Adhesion of Pseudomonas aeruginosa  

PubMed Central

Although ubiquitous, the processes by which bacteria colonize surfaces remain poorly understood. Here we report results for the influence of the wall shear stress on the early-stage adhesion of Pseudomonas aeruginosa PA14 on glass and polydimethylsiloxane surfaces. We use image analysis to measure the residence time of each adhering bacterium under flow. Our main finding is that, on either surface, the characteristic residence time of bacteria increases approximately linearly as the shear stress increases (?0–3.5 Pa). To investigate this phenomenon, we used mutant strains defective in surface organelles (type I pili, type IV pili, or the flagellum) or extracellular matrix production. Our results show that, although these bacterial surface features influence the frequency of adhesion events and the early-stage detachment probability, none of them is responsible for the trend in the shear-enhanced adhesion time. These observations bring what we believe are new insights into the mechanism of bacterial attachment in shear flows, and suggest a role for other intrinsic features of the cell surface, or a dynamic cell response to shear stress. PMID:21244830

Lecuyer, Sigolene; Rusconi, Roberto; Shen, Yi; Forsyth, Alison; Vlamakis, Hera; Kolter, Roberto; Stone, Howard A.



Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment  

Microsoft Academic Search

Rationale  There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA\\u000a agonists decreases cocaine self-administration.\\u000a \\u000a \\u000a \\u000a Objectives  The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole,\\u000a venlafaxine, or placebo.\\u000a \\u000a \\u000a \\u000a Methods  CD subjects enrolled in a treatment trial for cocaine dependence

Chris C. Streeter; John Hennen; Yong Ke; J. Eric Jensen; Ofra Sarid-Segal; Leanne E. Nassar; Clifford Knapp; Angela A. Meyer; Tae Kwak; Perry F. Renshaw; Domenic A. Ciraulo



Caffeine treatment prevents age-related changes in ovine oocytes and increases cell numbers in blastocysts produced by somatic cell nuclear transfer.  


Maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) are key regulators of both meiotic and mitotic cycles. Oocytes arrested at metaphase of the second meiotic division (MII) contain high levels of both kinases; however, these activities decline with age. Caffeine (an inhibitor of Myt1/Wee1 activity) can increase MPF and MAPK activities in ovine oocytes; however, the effects of caffeine treatment on the activation, nuclear configuration and developmental potential of ovine SC nuclear transfer (SCNT) embryos were unknown. We examined the effects of aging and caffeine treatment on MPF and MAPK activities, activation, development, and nuclear remodeling of SCNT embryos. Both kinases reached maximum activities at 24-h postonset of maturation (hpm) and then decreased with time. The decline in MPF activity occurred rapidly, whereas MAPK activity declined more slowly. Caffeine treatment (10.0 mM) of aging oocytes prevented the decline in activities associated with both kinases and prevented the acquisition of activation competence by a single activation stimulus. However, treatment of aged oocytes with caffeine could not increase kinase activities or reverse the acquisition of activation competence. Enucleation did not affect kinase activities, but caffeine treatment significantly increased both. Caffeine treatment did not affect the decline in MPF or MAPK activities following activation or significantly affect development of parthenogenetically activated oocytes. When SCNT reconstructed embryos were treated with caffeine following fusion, no increase in the frequency of development to blastocyst was observed; however, a significant increase in the occurrence of nuclear envelope break-down (NEBD) and an increase in total cell numbers occurred. PMID:18673075

Lee, Joon-Hee; Campbell, Keith H S



Effect of Treatment Time on the Microstructure of Austenitic Stainless Steel During Low-Temperature Liquid Nitrocarburizing  

NASA Astrophysics Data System (ADS)

The effect of treatment time on the microstructure of AISI 304 austenitic stainless steel during liquid nitrocarburizing (LNC) at 703 K (430 °C) was investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Experimental results revealed that the modified layer was covered with the alloy surface and the modified layer depth increased extensively from 2 to 33.4 ?m with increasing treatment time. SEM and XRD showed that when the 304 stainless steel sample was subjected to LNC at 703 K (430 °C) for less than 4 hours, the main phase of the modified layer was expanded austenite. When the treatment time was prolonged to 8 hours, the abundant expanded austenite was formed and it partially transformed into CrN and ferrite subsequently. With the increased treatment time, more and more CrN precipitate transformed in the overwhelming majority zone in the form of a typical dendritic structure in the nearby outer part treated for 40 hours. Still there was a single-phase layer of the expanded austenite between the CrN part and the inner substrate. TEM showed the expanded austenite decomposition into the CrN and ferrite after longtime treatment even at low temperature.

Wang, Jun; Lin, Yuanhua; Zhang, Qiang; Zeng, Dezhi; Fan, Hongyuan



Increasing Positive Outlook Partially Mediates the Effect of Empirically Supported Treatments on Depression Symptoms Among Adolescents  

PubMed Central

Among adolescents there is evidence that cognitive change partially mediates the effect of cognitive behavioral therapy (CBT) on depression outcome. However, prior studies have been limited by small samples, narrow measures of cognition, and failure to compare cognitive change following CBT to cognitive change following antidepressant medication. This study examined whether change in four cognitive constructs (cognitive distortions, cognitive avoidance, positive outlook, and solution-focused thinking) mediated change in depression severity in a sample of 291 adolescents who participated in the Treatment for Adolescents with Depression Study (TADS). TADS assessed the effects of CBT, fluoxetine, and their combination on depression severity. All three treatments were associated with change in the cognitive constructs and combination treatment produced the greatest change. Furthermore, change in the cognitive constructs partially mediated change in depression severity within all three treatments. Results implicated positive outlook as the construct most associated with change in depression severity over 36 weeks. PMID:24944436

Jacobs, Rachel H.; Becker, Sara J.; Curry, John F.; Silva, Susan G.; Ginsburg, Golda S.; Henry, David B.; Reinecke, Mark A.



Increased Oil Recovery from Mature Oil Fields Using Gelled Polymer Treatments  

SciTech Connect

This report describes the progress of the first year of a three-year research program. This program is aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production.

Willhite, G.P.; Green, D.W.; McCool, C.S.



Power Assigning Method for Increasing the Number of Users in Time-spreading Optical CDMA Systems  

NASA Astrophysics Data System (ADS)

In this paper, a method for increasing the number of supportable users in a time-spreading Optical code division multiple access (OCDMA) system is proposed. In the presented technique, a unique codeword is assigned to a couple of users instead of just one. Different optical powers are employed for such users in order to distinguish them from each other. Other methods use the frequency or the polarization of the optical signals as an additional coding dimension to increase the number of codewords and hence the number of users in the network. It is proposed to employ nonlinear optical regenerators for separating optical pulses with different powers. A comprehensive design algorithm for such regenerators is presented. In order to evaluate the performance of the designed regenerators a TS-OCDMA system is simulated using OptiSystem software. Results indicate an error free transmission in the system employing the proposed technique.

Salehi, Mohammad Reza; Abiri, Ebrahim; Kazemi, Keyvan; Dezfouli, Mehran



A method for verifying treatment times for simple high-dose-rate endobronchial brachytherapy procedures  

SciTech Connect

An empirical method for verifying the total treatment time for either a one- or a two-catheter high-dose-rate procedure has been developed. The method can be performed quickly and allows for easy verification of the accuracy of the treatment time arrived at by a computerized planning system. The method is designed to confirm the treatment time to within 10{percent}. {copyright} {ital 1996 American Association of Physicists in Medicine.}

Miller, A.V.; Davis, M.G.; Horton, J.L. [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)] [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)



Increasing the coherence time of single electron spins in diamond by high temperature annealing  

E-print Network

Negatively charged Nitrogen-Vacancy (NV$^-$) centers in diamond produced by ion implantation often show properties different from NVs created during the crystal growth. We observe that NVs created from nitrogen ions with four different energies (30-300 keV) show much shorter electron spin coherence time $T_2$ compared to the "natural" NVs and we could find any dependence of $T_2$ on the implantation energy. Moreover, we also find out that about 10% of them show switching from NV$^-$to NV$^0$. We develop a method to increase $T_2$ of single NV$^-$ centers by annealing the sample at $t=1200 {\\circ}$C whereas at the same time the fraction of the NVs showing discharging is greatly reduced.

Boris Naydenov; Friedemann Reinhard; Anke Lämmle; V. Richter; Rafi Kalish; Ulrika F. S. D'Haenens-Johansson; Mark Newton; Fedor Jelezko; Jörg Wrachtrup



Effects of increased low-level diode laser irradiation time on extraction socket healing in rats.  


In our previous studies, we confirmed that low-level laser therapy (LLLT) with a 980-nm gallium-aluminum-arsenide diode laser was beneficial for the healing of the alveolar bone in rats with systemic disease. However, many factors can affect the biostimulatory effects of LLLT. Thus, we attempted to investigate the effects of irradiation time on the healing of extraction sockets by evaluating the expressions of genes and proteins related to bone healing. The left and right first maxillary molars of 24 rats were extracted. Rats were randomly divided into four groups in which extraction sockets were irradiated for 0, 1, 2, or 5 min each day for 3 or 7 days. Specimens containing the sockets were examined using quantitative real-time reverse transcription polymerase chain reaction and western blotting. LLLT increased the expressions of all tested genes, Runx2, collagen type 1, osteocalcin, platelet-derived growth factor-B, and vascular endothelial growth factor, in a time-dependent manner. The highest levels of gene expressions were in the 5-min group after 7 days. Five minutes of irradiation caused prominent increases of the expression of all tested proteins after both 3 and 7 days. The expression level of each protein in group 4 was higher by almost twofold compared with group 1 after 7 days. Laser irradiation for 5 min caused the highest expressions of genes and proteins related to bone healing. In conclusion, LLLT had positive effects on the early stages of bone healing of extraction sockets in rats, which were irradiation time-dependent. PMID:23929563

Park, Joon Bong; Ahn, Su-Jin; Kang, Yoon-Goo; Kim, Eun-Cheol; Heo, Jung Sun; Kang, Kyung Lhi



Prostate and Patient Intrafraction Motion: Impact on Treatment Time-Dependent Planning Margins for Patients With Endorectal Balloon  

SciTech Connect

Purpose: To investigate intrafraction prostate and patient motion during different radiation therapy treatments as a function of treatment time; included were prostate patients with an endorectal balloon (ERB). Margins accounting for setup uncertainties and intrafraction motion were determined. Methods and Materials: The study included 17 patients undergoing prostate cancer radiation therapy. All patients received 3 fiducial gold markers implanted in the prostate and were then immobilized in the supine position with a knee support and treated with an ERB. Twelve patients with intermediate risk for pelvic lymph node metastases received intensity modulated radiation therapy (IMRT), and 5 patients at low risk received a 4-field box treatment. After setup based on skin marks, patients were imaged with a stereoscopic imaging system. If the marker displacement exceeded a 3-mm tolerance relative to planning computed tomography, patients were shifted and verification images were taken. All patients underwent additional imaging after treatment; IMRT patients also received additional imaging at halftime of treatment. Prostate and bone drifts were evaluated as a function of treatment time for more than 600 fractions, and margins were extracted. Results: Patient motion evaluated by bone match was strongly patient dependent but in general was smallest in the superior-inferior (SI) direction. Prostate drifts were less patient dependent, showing an increase with treatment time in the SI and anterior-posterior (AP) directions. In the lateral (LAT) direction, the prostate stayed rather stable. Mean treatment times were 5.5 minutes for 4-field box, 10 minutes for 5-field boost IMRT, and 15 minutes or more for 9-field boost and 9-field pelvic IMRT treatments. Margins resulted in 2.2 mm, 3.9 mm, and 4.3 mm for 4-field box; 3.7 mm, 2.6 mm, and 3.6 mm for 5-field boost IMRT; 2.3 mm, 3.9 mm, and 6.2 mm for 9-field boost IMRT; and 4.2 mm, 5.1 mm, and 6.6 mm for 9-field pelvic IMRT in the LAT, SI, and AP directions, respectively. Conclusion: Intrafraction prostate and patient displacement increased with treatment time, showing different behaviors for the single directions of movement. Repositioning of the patients during long treatments or shorter treatment times will be necessary to further reduce the treatment margin.

Steiner, Elisabeth, E-mail: [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria) [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Georg, Dietmar [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria) [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Goldner, Gregor [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria) [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Stock, Markus [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria) [Division of Medical Radiation Physics, Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria)



Can we explain increases in young people’s psychological distress over time?  

PubMed Central

This paper aims to explain previously described increases in self-reported psychological distress between 1987 and 2006 among samples identical in respect of age (15 years), school year and geographical location (West of Scotland). Such increases might be explained by changes in exposure (changes in levels of risk or protective factors) and/or by changes in vulnerability (changes in the relationship between risk/protective factors and psychological distress). Key areas of social change over this time period allow identification of potential explanatory factors, categorised as economic, family, educational, values and lifestyle and represented by variables common to each study. Psychological distress was measured via the 12-item General Health Questionnaire, Likert scored. Analyses were conducted on those with complete data on all variables (N = 3276 of 3929), and separately for males and females. Between 1987 and 2006, levels of almost every potential explanatory factor changed in line with general societal trends. Associations between explanatory factors and GHQ tended to be stronger among females, and at the later date. The strongest associations were with worries, arguments with parents, and, at the later date, school disengagement. The factors which best accounted for the increase in mean GHQ between 1987 and 2006 were arguments with parents, school disengagement, worry about school and, for females, worry about family relationships, reflecting both increasing exposure and vulnerability to these risk factors. A number of limitations to our analysis can be identified. However, our results reinforce the conclusions of others in highlighting the role of family and educational factors as plausible explanations for increases in young people’s psychological distress. PMID:20870334

Sweeting, Helen; West, Patrick; Young, Robert; Der, Geoff



Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.  


Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. PMID:20600981

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H



Timing is everything in the treatment of multiple sclerosis.  


We present two similar cases of relapsing-remitting multiple sclerosis, both of whom received treatment with the monoclonal antibody alemtuzumab, but had significantly different long-term outcomes. Patient A is 12?years into his illness and was treated early in his disease course, he has no disability and continues to perform at a high level as a professional golfer. Patient B was initially started on interferon-?1a therapy and went on to have two disabling relapses on this treatment which resulted in a degree of fixed disability prior to the start of alemtuzumab. 10?years into his disease course he has moderate disability and daily symptoms of spasticity in his legs which impair his quality of life. These two contrasting cases highlight the difficult decision of when to start potent immune modulating therapies for multiple sclerosis in young adults who appear well early in their disease but have the potential to rapidly accrue irreversible disability from future relapses. PMID:25878229

McCarthy, Claire Louise; Giovannoni, Gavin; Coles, Alasdair John



Ultrasound surgery using multiple sonications—Treatment time considerations  

Microsoft Academic Search

The noninvasive surgery of a tumor by focused transducers or phased arrays with multiple sonications was simulated in this study. The effects of multiple sonications on near field heating were investigated by varying the delay time between consecutive pulses and the movement pattern of the transducer within the focal plane. To avoid normal tissue damage, sufficient delay time between consecutive

Xiaobing Fan; Kullervo Hynynen



Malic acid or orthophosphoric acid-heat treatments for protecting sunflower (Helianthus annuus) meal proteins against ruminal degradation and increasing intestinal amino acid supply.  


The protection of sunflower meal (SFM) proteins by treatments with solutions of malic acid (1 M) or orthophosphoric acid (0.67 M) and heat was studied in a 3 × 3 Latin-square design using three diets and three rumen and duodenum cannulated wethers. Acid solutions were applied to SFM at a rate of 400 ml/kg under continuous mixing. Subsequently, treated meals were dried in an oven at 150°C for 6 h. Diets (ingested at 75 g/kg BW0.75) were isoproteic and included 40% Italian ryegrass hay and 60% concentrate. The ratio of untreated to treated SFM in the concentrate was 100 : 0 in the control diet and around 40 : 60 in diets including acid-treated meals. The use of acid-treated meals did not alter either ruminal fermentation or composition of rumen contents and led to moderate reductions of the rumen outflow rates of untreated SFM particles, whereas it did not affect their comminution and mixing rate. In situ effective estimates of by-pass (BP) and its intestinal effective digestibility (IED) of dry matter (DM), CP and amino acids (AAs) were obtained considering both rates and correcting the particle microbial contamination in the rumen using 15N infusion techniques. Estimates of BP and IED decreased applying microbial correction, but these variations were low in agreement with the small contamination level. Protective treatments increased on average the BP of DM (48.5%) and CP (267%), mainly decreasing both the soluble fraction and the degradation rate but also increasing the undegradable fraction, which was higher using orthophosphoric acid. Protective treatments increased the IED of DM (108%) and CP, but this increase was lower using orthophosphoric acid (11.8%) than malic acid (20.7%). Concentrations of AA were similar among all meals, except for a reduction in lysine concentrations using malic acid (16.3%) or orthophosphoric acid (20.5%). Protective treatments also increased on average the BP of all AA, as well as the IED of most of them. Evidence of higher increases for those AA showing a high resistance to degradation in the untreated meal were also observed. The total supply of metabolisable AA was increased by 3.87 times for sulphur-containing AA, whereas that of lysine was increased by 2.5 times, mainly because of lysine losses with heat treatments. These treatments and especially that with malic acid would be useful to increase the protein value of these meals but their combined use with lysine-rich protein concentrates would improve the metabolisable protein profile. PMID:23032153

Arroyo, J M; González, J; Ouarti, M; Silván, J M; Ruiz del Castillo, M L; de la Peña Moreno, F



Childhood Adversity Accelerates Intended Reproductive Timing in Adolescent Girls without Increasing Interest in Infants  

PubMed Central

Women experiencing greater childhood adversity exhibit faster reproductive trajectories. One possible psychological mechanism underlying this phenomenon is an increased interest in infants. Interest in infants is thought to be an adaptation important for successful rearing as it motivates the acquisition of caretaking skills. We investigated the relationships between childhood adversity, intended reproductive timing and interest in infants in a sample of English adolescent girls. Specifically we sought to investigate the relationship between 1) childhood adversity and intended reproductive timing; 2) childhood adversity and interest in infants; and 3) intended reproductive timing and interest in infants. Additionally we explored different methods of measuring interest in infants using self-reported fondness for babies, a forced choice adult versus infant paper-based preference task and a novel computer based attention task using adult and infant stimuli. In total 357 girls aged nine to 14 years participated in the study, which took place in schools. Participants completed the two interest in infants tasks before moving on to a childhood adversity questionnaire. Girls with more childhood adversity reported earlier ideal ages at parenthood. We found some evidence that, contrary to our predictions, girls with less childhood adversity were more interested in infants. There was no relationship between intended reproductive timing and interest in infants. The different measurements for interest in infants were only weakly related, if at all, highlighting the complexity of measuring this construct. Our findings suggest that rather than interest in infants being a mechanism for the effect of childhood adversity on early reproductive timing it might instead be an indicator of future reproductive strategies. PMID:24454778

Clutterbuck, Stephanie; Adams, Jean; Nettle, Daniel



Older women with localized breast cancer: costs and survival rates increased across two time periods.  


Significant national attention has been paid to the rising costs of cancer care. However, few studies have evaluated the association between trends in costs and survival outcomes. We used the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare linked database to compare changes in costs and survival rates over time, among women ages 67-94 who were diagnosed with stage II or III breast cancer in 1994-96 or 2004-06. We found that median cancer-related costs increased from $12,335 to $17,396 among women with stage II disease, and from $18,107 to $32,598 among women with stage III disease. Although the median cost of breast surgery declined between the two study periods, the median cost of chemo- and radiation therapy increased substantially, leading to an overall rise in cancer-related costs. Meanwhile, adjusted overall five-year survival improved, from 67.8 percent to 72.5 percent for women with stage II disease and from 38.5 percent to 51.9 percent for those with stage III disease. These findings suggest that increases in cancer care costs have been accompanied by improved outcomes. Future work should identify opportunities to optimize efficiency in cancer care. PMID:25847641

Feinstein, Aaron J; Long, Jessica; Soulos, Pamela R; Ma, Xiaomei; Herrin, Jeph; Frick, Kevin D; Chagpar, Anees B; Krumholz, Harlan M; Yu, James B; Ross, Joseph S; Gross, Cary P



Effect of Camellia sinensis supplementation and increasing holding time on quality of cryopreserved boar semen.  


Cryopreservation of boar semen is still considered suboptimal due to the low fertility when compared with fresh semen. This study was performed to evaluate the effects of green tea (Camellia sinensis) supplementation of the freezing extender at different concentration (0, 2.5%, 5%, 10%) and also to determine the influence of increasing holding time from 2 to 24 h at 15 °C. Seventeen ejaculates from nine boars were used to make pools of three of them and then cryopreserved. Sperm motility, viability, acrosome integrity, membrane functionality (HOST) and capacitation status were determined before freezing and at 0, 30, 60, 90 and 120 min after thawing. Lipid peroxidation was evaluated just after thawing. The main findings emerging from this study were the following: (i) no improvement in quality of thawed spermatozoa with addition of tea to the freezing extender, (ii) no improvement in quality of thawed spermatozoa with prolonged holding time, (iii) lower peroxidation rate in presence of tea 5% and (iv) a decrease in the number of uncapacited viable spermatozoa with any tea supplementation. We conclude that amplification of holding time in semen cryopreservation process does not vary results, facilitating freezing protocol. Tea supplementation reduces lipoxidation but did not improve quality parameters. PMID:24909203

Gale, I; Gil, L; Malo, C; González, N; Martínez, F



Dialysis access venous stenosis: treatment with balloon angioplasty 30-second vs. 1-minute inflation times.  


Percutaneous balloon angioplasty is the standard of care in the endovascular treatment of dialysis access venous stenosis. The significance of balloon inflation times in the treatment of these stenoses is not well defined. Our objective was to examine the outcomes of 30-second vs. 1-minute balloon inflation times on primary-assisted patency of arteriovenous fistulae and grafts. Using a prospectively collected vascular access database, we identified a total of 75 patients referred for access dysfunction during a 5-year period. These patients received 223 interventions (178 with 30-second inflations and 45 with 1-minute inflations). We compared primary-assisted patency during the subsequent 9 months across groups defined by inflation times. Demographics and baseline characteristics were similar across groups. Immediate technical success and patency in the first 3 months were similar across groups (hazard ratio [HR]?=?0.86; 95% confidence interval [CI]: 0.34-2.20). After 3 months, however, a 1-minute inflation time was associated with greater incidence of access failure (adjusted HR [aHR]?=?1.74; 95% CI: 1.09-2.79). Other predictors of access failure included age over 60 (aHR?=?1.02; 95% CI: 1.01-1.04), central location of the lesion (aHR?=?2.49; CI: 1.27-4.89), and three or more prior procedures (aHR 2.48; CI: 1.19-5.16). Our data suggest that shorter balloon inflation times may be associated with improved longer term access patency, although the benefit was not observed until after 3 months. Given the increasing demands of maintaining access patency in the era of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Fistula First, the role of angioplasty times requires further study. PMID:24888749

Elramah, Mohsen; Boujelbane, Lamya; Yevzlin, Alexander S; Wakeen, Maureen; Astor, Brad C; Chan, Micah R



nCPAP Treatment of Obstructive Sleep Apnea Increases Slow Wave Sleep in Prefrontal EEG  

Microsoft Academic Search

According to standard sleep stage scoring, sleep EEG is studied from the central area of parietal lobes. However, slow wave sleep (SWS) has been found to be more powerful in frontal areas in healthy subjects. Obstructive sleep apnea syndrome (OSAS) patients often suffer from functional disturbances in prefrontal lobes.We studied the effects of nasal Continuous Positive Airway Pressure (nCPAP) treatment

Veera Eskelinen; Toomas Uibu; Sari-Leena Himanen



Treatment Fidelity of Motivational Interviewing Delivered by a School Nurse to Increase Girls' Physical Activity  

ERIC Educational Resources Information Center

Motivational interviewing, which involves the use of person-centered, directive counseling techniques, shows promise for changing adolescent behaviors. The purpose of this article was to describe the methodology and findings related to the treatment fidelity of three face-to-face motivational interviewing sessions involving middle school girls and…

Robbins, Lorraine B.; Pfeiffer, Karin A.; Maier, Kimberly S.; LaDrig, Stacey M.; Berg-Smith, Steven Malcolm



Ways of Increasing the Operating Reliability of the Equipment of a Gas Treatment Plant  

Microsoft Academic Search

Now that the acid gas removal equipment of the Astrakhan Gas Treatment Plant (AGTP) has reached its design operating life, it has become necessary to evaluate the residual life and extension of the service life of that equipment. The major ity of the failures of that equipment is due to corrosion. Accordingly, it was necessary to investigate the degree of

V. V. Gur'yanov; M. L. Medvedeva



Adjuvant oestrogen treatment increases bone mineral density in postmenopausal women with rheumatoid arthritis  

Microsoft Academic Search

OBJECTIVES--The beneficial effect of oestrogens on bone mineral density in women with osteoporosis is well known. Patients with rheumatoid arthritis (RA) are at risk for osteoporosis. A study was therefore set up to investigate the effects of adjuvant oestrogen treatment on bone metabolism and bone mineral density in postmenopausal women with RA. METHODS--Forty postmenopausal women with active RA were admitted

H R van den Brink; W F Lems; A A van Everdingen; J W Bijlsma



Beyond on/off: Increasing the benefits of patch spraying with multiple treatments  

Technology Transfer Automated Retrieval System (TEKTRAN)

Site-specific weed management can encompass both limiting treatment to areas of the field where weed pressure is above the economic threshold (patch spraying) and varying the choice of herbicide for most cost-effective weed control of local populations. The potential benefits of patch spraying with ...


Genotypic diversity effects on the performance of Taraxacum officinale populations increase with time and environmental favorability.  


Within-population genetic diversity influences many ecological processes, but few studies have examined how environmental conditions may impact these short-term diversity effects. Over four growing seasons, we followed experimental populations of a clonal, ubiquitous weed, Taraxacum officinale, with different numbers of genotypes in relatively favorable fallow field and unfavorable mowed lawn environmental treatments. Population performance (measured as total leaf area, seed production or biomass) clearly and consistently increased with diversity, and this effect became stronger over the course of the experiment. Diversity effects were stronger, and with different underlying mechanisms, in the fallow field versus the mowed lawn. Large genotypes dominated in the fallow field driving overyielding (via positive selection effects), whereas in the mowed lawn, where performance was limited by regular disturbance, there was evidence for complementarity among genotypes (with one compact genotype in particular performing better in mixture than monoculture). Hence, we predict stronger genotypic diversity effects in environments where intense intraspecific competition enhances genotypic differences. Our four-year field experiment plus seedling establishment trials indicate that genotypic diversity effects have far-reaching and context-dependent consequences across generations. PMID:22348004

Drummond, Emily B M; Vellend, Mark



TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders  

PubMed Central

Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x109/L. A reduction of platelets to <600 in asymptomatic or <400 x 109/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD. PMID:18414650

Palmblad, Jan; Björkholm, Magnus; Kutti, Jack; Lärfars, Gerd; Löfvenberg, Eva; Markevärn, Berit; Merup, Mats; Mauritzson, Nils; Westin, Jan; Samuelsson, Jan; Birgegård, Gunnar



Systemic and Cerebral Vascular Endothelial Growth Factor Levels Increase in Murine Cerebral Malaria along with Increased Calpain and Caspase Activity and Can be Reduced by Erythropoietin Treatment  

PubMed Central

The pathogenesis of cerebral malaria (CM) includes compromised microvascular perfusion, increased inflammation, cytoadhesion, and endothelial activation. These events cause blood–brain barrier disruption and neuropathology and associations with the vascular endothelial growth factor (VEGF) signaling pathway have been shown. We studied this pathway in mice infected with Plasmodium berghei ANKA causing murine CM with or without the use of erythropoietin (EPO) as adjunct therapy. ELISA and western blotting was used for quantification of VEGF and relevant proteins in brain and plasma. CM increased levels of VEGF in brain and plasma and decreased plasma levels of soluble VEGF receptor 2. EPO treatment normalized VEGF receptor 2 levels and reduced brain VEGF levels. Hypoxia-inducible factor (HIF)-1? was significantly upregulated whereas cerebral HIF-2? and EPO levels remained unchanged. Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of ?-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HIF-1?, which in the brain were reduced to normal in EPO-treated mice. Also caspase and calpain activity was reduced markedly in EPO-treated mice. PMID:24995009

Hempel, Casper; Hoyer, Nils; Kildemoes, Anna; Jendresen, Charlotte Bille; Kurtzhals, Jørgen Anders Lindholm



Does dimethicone increase the efficacy of antacids in the treatment of reflux oesophagitis?  

PubMed Central

Dimethicone is a common additive to antacids, although its value in the treatment of reflux oesophagitis is unproven. Its efficacy was assessed by comparing the effect of a dimethicone-containing antacid gel (Asilone Gel) with a simple antacid gel in a double-blind trial in 45 patients with reflux oesophagitis. Thirty-eight patients completed the eight-week course of therapy. Antacid therapy alone resulted in a significant improvement of both symptoms and oesophagitis in gastro-oesophageal reflux. The inclusion of dimethicone in the antacid gel preparation did not confer any benefit in terms of symptomatic assessment but did confer a small advantage with regard to objective markers of oesophageal inflammation, suggesting that a dimethicone-containing antacid is of value in the treatment of symptomatic gastro-oesophageal reflux. PMID:3537288

Ogilvie, A L; Atkinson, M



Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.  


Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. PMID:25320342

Heemskerk, Mattijs M; Dharuri, Harish K; van den Berg, Sjoerd A A; Jónasdóttir, Hulda S; Kloos, Dick-Paul; Giera, Martin; van Dijk, Ko Willems; van Harmelen, Vanessa



Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model.  


An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. (18)F-fluorothymidine ((18)F-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'-deoxythymidine ((3)H-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. (3)H-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral (3)H-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral (3)H-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib. PMID:24137387

Murakami, Masahiro; Zhao, Songji; Zhao, Yan; Yu, Wenwen; Fatema, Chowdhury Nusrat; Nishijima, Ken-Ichi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi; Tamaki, Nagara; Kuge, Yuji



Short-term training increases diagnostic and treatment rate for insomnia in general practice  

Microsoft Academic Search

Summary  \\u000a Objective To evaluate the effect of short-term training of general practitioners (GPs) on their diagnosis and treatment of chronic\\u000a insomnia. Methods A three-step randomized control group design was used: After baseline evaluation (T1) a group of 9 GPs underwent a training\\u000a of half a day, while 7 GPs served as a control group. The diagnostic and therapeutic handling of

Jutta Backhaus; Klaus Junghanns; Kristin Mueller-Popkes; Andreas Broocks; Dieter Riemann; Goeran Hajak; Fritz Hohagen



Neonatal Iron Treatment Increases Apoptotic Markers in Hippocampal and Cortical Areas of Adult Rats  

Microsoft Academic Search

Oxidative stress, cellular damage, and neuronal apoptosis are believed to underlie the progressive cognitive decline that\\u000a accompanies natural aging and to be exacerbated in neurodegenerative diseases. Over the years, we have consistently demonstrated\\u000a that iron neonatal treatment induces oxidative stress and memory deficits in adult rats, but the mechanisms underlying these\\u000a effects remained undefined. The purpose of this study was

Clivia Pazin Miwa; Maria Noêmia Martins de Lima; Felipe Scalco; Gustavo Vedana; Raquel Mattos; Liana Lisboa Fernandez; Arlete Hilbig; Nadja Schröder; Monica R. M. Vianna



HIV Treatment Produces Economic Returns Through Increased Work And Education, And Warrants Continued US Support  

PubMed Central

Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President’s Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment. PMID:22778336

Thirumurthy, Harsha; Galárraga, Omar; Larson, Bruce; Rosen, Sydney



Short-term steroid treatment increases delta GABAA receptor subunit expression in rat CA1 hippocampus: pharmacological and behavioral effects.  


In this study, 48 h administration of 3alpha-OH-5beta-pregnan-20-one (3alpha,5beta-THP) or 17beta-estradiol (E2)+progesterone (P) to female rats increased expression of the delta subunit of the GABA(A) receptor (GABAR) in CA1 hippocampus. Coexpression of alpha4 and delta subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7- tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 microM lanthanum (La3+). Because alpha4betadelta GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La3+-sensitive THIP current, representative of current gated by alpha4betadelta GABAR, was measurable only following 48 h steroid treatment. In contrast, the bicuculline-sensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48 h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 microM) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of alpha4betadelta GABAR which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48 h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle. PMID:15950994

Shen, Hui; Gong, Qi Hua; Yuan, Maoli; Smith, Sheryl S



The treatment of overdose--time for a change?  


To determine emergency management of overdose relating to gastrointestinal decontamination procedures in Scottish Accident & Emergency (A & E) Departments. A postal questionnaire was sent to the 28 main A & E Departments in Scotland. There was a 75% response rate. Nineteen departments(90%) continue to perform gastric lavage, with the majority carrying out this procedure more than one hour post-ingestion of commonly presenting overdoses. Sixteen departments (76%) regularly administer activated charcoal and four (19%) use syrup of ipecacuanha. Twenty departments (95%) had access to Toxbase. The majority of respondents (86%) feel there is a need for standardisation of treatment in acute overdose. Despite the availability of guidelines provided by the UK National Poisons Information Service and the Position Statements, there is no consensus in the actual management of acute overdose among Scottish A&E departments. PMID:10986740

McGuffie, A C; Wilkie, S C; Kerr, G W



Progressive increases in bone mass and bone strength in an ovariectomized rat model of osteoporosis after 26 weeks of treatment with a sclerostin antibody.  


The effects of up to 26 weeks of sclerostin antibody (Scl-Ab) treatment were investigated in ovariectomized (OVX) rats. Two months after surgery, 6-month-old osteopenic OVX rats were treated with vehicle or Scl-Ab (25 mg/kg, sc, one time per week) for 6, 12, or 26 weeks. In vivo dual-energy x-ray absorptiometry analysis demonstrated that the bone mineral density of lumbar vertebrae and femur-tibia increased progressively through 26 weeks of Scl-Ab treatment along with progressive increases in trabecular and cortical bone mass and bone strength at multiple sites. There was a strong correlation between bone mass and maximum load at lumbar vertebra, femoral neck, and diaphysis at weeks 6 and 26. Dynamic histomorphometric analysis showed that lumbar trabecular and tibial shaft endocortical and periosteal bone formation rates (BFR/BS) increased and peaked at week 6 with Scl-Ab-treatment; thereafter trabecular and endocortical BFR/BS gradually declined but remained significantly greater than OVX controls at week 26, whereas periosteal BFR/BS returned to OVX control levels at week 26. In the tibia metaphysis, trabecular BFR/BS in the Scl-Ab treated group remained elevated from week 6 to week 26. The osteoclast surface and eroded surface were significantly lower in Scl-Ab-treated rats than in OVX controls at all times. In summary, bone mass and strength increased progressively over 26 weeks of Scl-Ab treatment in adult OVX rats. The early gains were accompanied by increased cortical and trabecular bone formation and reduced osteoclast activity, whereas later gains were attributed to residual endocortical and trabecular osteoblast stimulation and persistently low osteoclast activity. PMID:25259718

Li, Xiaodong; Niu, Qing-Tian; Warmington, Kelly S; Asuncion, Franklin J; Dwyer, Denise; Grisanti, Mario; Han, Chun-Ya; Stolina, Marina; Eschenberg, Michael J; Kostenuik, Paul J; Simonet, William S; Ominsky, Michael S; Ke, Hua Zhu



Rapid increases and time-lagged declines in amphibian occupancy after wildfire  

USGS Publications Warehouse

Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ? 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region.

Hossack, Blake R.; Lowe, Winsor H.; Corn, Paul Stephen



Rapid increases and time-lagged declines in amphibian occupancy after wildfire.  


Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ? 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region. PMID:22978248

Hossack, Blake R; Lowe, Winsor H; Corn, Paul Stephen



Deficits in reaction time due to increased motor time of peroneus longus in people with chronic ankle instability.  


The purpose of this study was to investigate whether neuromuscular adaptations at the site of injury or neural adaptation remote to the injury are affected in individuals with chronic ankle instability (CAI). Electromyography data were collected from the peroneus longus (PL) and tibialis anterior during an ankle joint reaction time task in 12 participants with unilateral CAI and 12 healthy control participants. Following an auditory cue, time to onset of muscle activity (pre-motor time) and time from onset of muscle activity to movement (motor time) were measured during rapid ankle eversion and dorsiflexion. Reaction time for ankle eversion on the affected side was significantly slower in the CAI group than the control group, due to significantly slower motor time for the PL. Changes in motor time for the affected PL in participants with CAI may be attributed to a combination of factors associated with local tissue changes. PMID:22177674

Kavanagh, Justin J; Bisset, Leanne M; Tsao, Henry



Postimpoundment time course of increased mercury concentrations in fish in hydroelectric reservoirs of northern Manitoba, Canada.  


Mercury (Hg) concentrations in fish in boreal reservoirs have been shown to be increased for up to 3 decades after impoundment. However, the time course of increased concentrations is not well known. The purpose of this study was to determine the evolution of Hg concentrations in fish in the boreal reservoirs of northern Manitoba, Canada, and its relationship with severity of flooding. We determined total Hg concentrations in three species of fish for up to 35 years after impoundment in 14 lakes and lake basins. Postimpoundment trends depended on fish species and reservoir. In the benthivorous lake whitefish (Coregonus clupeaformis), Hg concentrations increased after flooding to between 0.2 and 0.4 microg g(-1) wet weight compared with preimpoundment concentrations between 0.06 and 0.14 microg g(-1) and concentrations in natural lakes between 0.03 and 0.06 microg g(-1). Hg concentrations in lake whitefish were usually highest within 6 years after lake impoundment and took 10 to 20 years after impoundment to decrease to background concentrations in most reservoirs. Hg concentrations in predatory northern pike (Esox lucius) and walleye (Sander vitreus) were highest 2 to 8 years after flooding at 0.7 to 2.6 microg g(-1) compared with preimpoundment concentrations of 0.19 to 0.47 microg g(-1) and concentrations in natural lakes of 0.35 to 0.47 microg g(-1). Hg concentrations in these predatory species decreased consistently in subsequent years and required 10 to 23 years to return to background levels. Thus, results demonstrate the effect of trophic level on Hg concentrations (biomagnification). Peak Hg concentrations depended on the amount of flooding (relative increase in lake surface area). Asymptotic concentrations of approximately 0.25 microg g(-1) for lake whitefish and 1.6 microg g(-1) for both walleye and northern pike were reached at approximately 100% flooding. Downstream effects were apparent because many reservoirs downstream of other impoundments had higher Hg concentrations in fish than would be expected on the basis of flooding amount. PMID:17728990

Bodaly, R A Drew; Jansen, W A; Majewski, A R; Fudge, R J P; Strange, N E; Derksen, A J; Green, D J



Biochemical and histopathological changes induced by different time intervals of methomyl treatment in mice liver.  


The present study was designed to evaluate the toxic effects induced by different time intervals of methomyl exposure on liver antioxidant defense system, oxidative stress, liver function biomarkers and histopathology in CD-1 mice. Ten male mice per group were assigned to one of four treatment groups. Group one served as control while group 2, 3 and 4 were orally treated with one mg methomyl/kg BW for 10, 20 and 30 days, respectively. Results obtained showed that methomyl significantly induced TBARS and decreased the activity of antioxidant enzymes, glutathione S-transferase, superoxide dismutase and catalase and the levels of reduced glutathione in mice liver. Aminotransferases and alkaline phosphatase activities were significantly decreased in liver due to methomyl administration, while the activities of these enzymes were significantly increased in serum. In addition, liver lactate dehydrogenase activity was significantly increased. On the contrary, methomyl treatment caused a significant decrease in liver acid phosphatase. The histology of mice liver treated with methomyl for 10, 20 and 30 days of duration showed dilation of central vein, sinusoids between hypertrophied hepatocytes and nuclear degeneration with mononuclear cell infiltration. In conclusion, exposure to methomyl induced toxicity and oxidative stress in mice liver via free radicals mechanism. Also, methomyl might have affected cell metabolism, cell membrane permeability and the detoxification system in liver. PMID:22755542

El-Demerdash, Fatma; Attia, Azza A; Elmazoudy, Reda H



Development of a Multilevel Framework to Increase Use of Targeted Evidence-Based Practices in Addiction Treatment Clinics  

PubMed Central

Implementing specific evidence-based practices (EBPs) across a set of addiction treatment providers have been a persistent challenge. In the Advancing Recovery(AR) demonstration project, single state agencies, the entities that distribute federal funds for substance use disorder prevention and treatment services, worked in partnership with providers to increase the use of EBPs in the treatment of addiction. The project supported two cohorts of six 2-year awards. Field observations from the first year of implementation guided development of a multilevel framework (the Advancing Recovery Framework). Government entities and other payers can use the framework as a guide for implementing evidence-based clinical practices within treatment networks. The Advancing Recover Framework calls for a combination of policy and organizational changes at both the payer (government agency) and provider levels. Using the Advancing Recovery Framework, 11 of the 12 AR payer/provider partnerships increased use of clinical EPBs. This article identifies key payer policy changes applied during different phases of EBP program implementation. The public health benefit of the demonstration project was broader use of medication–assisted therapy and continuing care in addiction treatment services. PMID:24955331

Molfenter, Todd; McCarty, Dennis; Capoccia, Victor; Gustafson, David



BH4 treatment in BH4-responsive PKU patients: preliminary data on blood prolactin concentrations suggest increased cerebral dopamine concentrations.  


In phenylketonuria (PKU), cerebral neurotransmitter deficiencies have been suggested to contribute to brain dysfunction. Present treatment aims to reduce blood phenylalanine concentrations by a phenylalanine-restricted diet, while in some patients blood phenylalanine concentrations also respond to cofactor treatment with tetrahydrobiopterin (BH4). Recently, a repurposing approach of BH4 was suggested to increase cerebral neurotransmitter synthesis. To investigate whether BH4 may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, we investigated blood prolactin concentrations-as a parameter of brain dopamine availability. We retrospectively compared blood prolactin in relation to blood phenylalanine concentrations of nine (male) BH4-responsive PKU patients, when being treated without and with BH4. Blood prolactin concentrations positively correlated to blood phenylalanine concentrations (p=0.002), being significantly lower with than without BH4 treatment (p=0.047). In addition, even in this small number of male patients, blood prolactin concentrations tended to be lower at increasing BH4 dose (p=0.054), while taking blood phenylalanine concentrations into account (p=0.002). In individual BH4-responsive patients, median blood prolactin concentrations were significantly lower while using BH4 than before using BH4 treatment (p=0.024), whereas median blood phenylalanine concentrations tended to be lower, but this did not reach statistical significance (p=0.107). Therefore, these data show that high blood phenylalanine in BH4-responsive PKU male patients seems to be associated with increased blood prolactin concentrations, suggesting reduced cerebral dopamine availability. Moreover, these data suggest that BH4 treatment in itself could decrease blood prolactin concentrations in a dose-responsive way, independent of blood phenylalanine concentrations. We conclude that these preliminary data indicate that BH4 treatment may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, possibly in a dose-dependent manner, but further research would be warranted. PMID:25466353

van Vliet, Danique; Anjema, Karen; Jahja, Rianne; de Groot, Martijn J; Liemburg, Geertje B; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; Derks, Terry G J; Kema, Ido P; van Spronsen, Francjan J



Limited increase in primary HIV-1C drug resistance mutations in treatment naïve individuals in Ethiopia.  


Antiretroviral drug resistance is a major challenge for management and control of HIV-1 infection worldwide and particularly in resource limited countries. The frequency of primary drug resistance mutations (DRMs) and of naturally occurring polymorphisms was determined in 83 antiretroviral treatment (ART) naïve Ethiopian individuals infected with HIV-1, consecutively enrolled in 2010. In all individuals HIV-1C was found. The median (interquartile range) of CD4(+) T-cell count and viral load were 100 (49-201) cells/?l and 44,640 (12,553-134,664) copies/ml, respectively. Protease (PR) and reverse transcriptase (RT) genes of HIV-1 RNA were amplified and sequenced. The proportion of primary DRM to any drug class, using the World Health Organization mutation lists, was 7.2% (6/83), thus exceeding the WHO threshold limit of 5%. Three individuals (3.6%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, two individuals (2.4%) had protease inhibitor mutations, and one (1.2%) had mutations associated with two drug classes (nucleoside reverse transcriptase inhibitor and NNRTI). In addition, the frequency of polymorphisms in the PR and RT genes was higher compared with previous studies in Ethiopian as well as worldwide isolates. Hence, genotypic drug resistance testing as part of routine management of individuals seems reasonable even in resource limited countries prior to treatment in order to allow proper choice of ART. J. Med. Virol. 87:978-984, 2015. © 2015 Wiley Periodicals, Inc. PMID:25649964

Huruy, Kahsay; Maier, Melanie; Mulu, Andargachew; Liebert, Uwe G



Conditional TGF-?1 treatment increases stem cell-like cell population in myoblasts  

PubMed Central

The limitation in successfully acquiring large populations of stem cell has impeded their application. A new method based on the dedifferentiation of adult somatic cells to generate induced multipotent stem cells would allow us to obtain a large amount of autologous stem cells for regenerative medicine. The current work was proposed to induce a sub-population of cells with characteristics of muscle stem cells from myoblasts through conditional treatment of Transforming Growth Factor (TGF)-?1. Our results show that a lower concentration of TGF-?1 is able to promote C2C12 myoblasts to express stem cell markers as well as to repress myogenic proteins, which involves a mechanism of dedifferentiation. Moreover, TGF-?1 treatment promoted the proliferation-arrested C2C12 myoblasts to re-enter the S-phase. We also investigated the multi-differentiation potentials of the dedifferentiated cells. TGF-?1 pretreated C2C12 myoblasts were implanted into mice to repair dystrophic skeletal muscle or injured bone. In addition to the C2C12 myoblasts, similar effects of TGF-?1 were also observed in the primary myoblasts of mice. Our results suggest that TGF-?1 is effective as a molecular trigger for the dedifferentiation of skeletal muscle myoblasts and could be used to generate a large pool of progenitor cells that collectively behave as multipotent stem cell-like cells for regenerative medicine applications. PMID:20184662

Mu, Xiaodong; Li, Yong



Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa.  


We investigated the emergence and evolution of drug-resistant tuberculosis (TB) in an HIV co-infected population at a South African gold mine with a well-functioning TB control program. Of 128 patients with drug-resistant TB diagnosed during January 2003-November 2005, a total of 77 had multidrug-resistant (MDR) TB, 26 had pre-extensively drug-resistant TB (XDR TB), and 5 had XDR TB. Genotyping suggested ongoing transmission of drug-resistant TB, and contact tracing among case-patients in the largest cluster demonstrated multiple possible points of contact. Phylogenetic analysis demonstrated stepwise evolution of drug resistance, despite stringent treatment adherence. These findings suggested that existing TB control measures were inadequate to control the spread of drug-resistant TB in this HIV co-infected population. Diagnosis delay and inappropriate therapy facilitated disease transmission and drug-resistance. These data call for improved infection control measures, implementation of rapid diagnostics, enhanced active screening strategies, and pharmacokinetic studies to determine optimal dosages and treatment regimens. PMID:20113557

Calver, Alistair D; Falmer, Alecia A; Murray, Megan; Strauss, Odelia J; Streicher, Elizabeth M; Hanekom, Madelene; Liversage, Thelma; Masibi, Mothusi; van Helden, Paul D; Warren, Robin M; Victor, Thomas C



Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism  

SciTech Connect

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr. (Massachusetts General Hospital, Boston (USA))



Men at low-risk of dying from their prostate cancer increasingly opting for advanced treatment options

For men with a low risk of dying from their prostate cancer, advanced treatment options may offer little to no benefit, yet more and more patients are opting for these procedures. A new study from the University of Michigan Comprehensive Cancer Center examined Medicare data between 2004 and 2009 for men with prostate cancer whose disease was low-risk or those who were at a high risk to die from other causes. The researchers found that these men increasingly underwent advanced treatment options, such as intensity-modulated radiotherapy and robotic prostatectomy.


The fan effect refers to an increase in response time and/or error rates on a memory test with an increase in the  

E-print Network

The fan effect refers to an increase in response time and/or error rates on a memory test assumed to "fan" out of the concept node, hence the name. Since its first demon- stration by Anderson (1974), the fan effect has been repli- cated in many different experimental paradigms with dif- ferent

Reder, Lynne


Temperature, plant species and residence time effects on nitrogen removal in model treatment wetlands.  


Total nitrogen (TN) removal in treatment wetlands (TWs) is challenging due to nitrogen cycle complexity and the variation of influent nitrogen species. Plant species, season, temperature and hydraulic loading most likely influence root zone oxygenation and appurtenant nitrogen removal, especially for ammonium-rich wastewater. Nitrogen data were collected from two experiments utilizing batch-loaded (3-, 6-, 9- and 20-day residence times), sub-surface TWs monitored for at least one year during which temperature was varied between 4 and 24 °C. Synthetic wastewater containing 17 mg/l N as NH4 and 27 mg/l amino-N, 450 mg/l chemical oxygen demand (COD), and 13 mg/l SO4-S was applied to four replicates of Carex utriculata, Schoenoplectus acutus and Typha latifolia and unplanted controls. Plant presence and species had a greater effect on TN removal than temperature or residence time. Planted columns achieved approximately twice the nitrogen removal of unplanted controls (40-95% versus 20-50% removal) regardless of season and temperature. TWs planted with Carex outperformed both Typha and Schoenoplectus and demonstrated less temperature dependency. TN removal with Carex was excellent at all temperatures and residence times; Schoenoplectus and Typha TN removal improved at longer residence times. Reductions in TN were not accompanied by increases in NO3, which was consistently below 1 mg/l N. PMID:24334880

Allen, C R; Stein, O R; Hook, P B; Burr, M D; Parker, A E; Hafla, E C



Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid  

PubMed Central

OBJECTIVE—To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.?DESIGN—Randomised, double blind, placebo controlled, crossover trial.?METHODS—Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.?RESULTS—There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (?3.5% to 10.4%) and ?0.9% (?4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.?CONCLUSION—This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.?? PMID:9771245

Garrett, J; Williams, S; Wong, C; Holdaway, D



Neonatal Treatment with Monosodium Glutamate Increases Plasma Corticosterone in the Rat  

Microsoft Academic Search

Monosodium glutamate (MSG) has been shown to alter several neuroendocrine functions in neonatally treated rats. To evaluate for possible alterations in the hypothalamic-pituitary-adrenal axis, we injected rats during the neonatal period with MSG or saline (controls). An increase in basal plasma corticosterone levels associated with a blunted circadian variation was observed. Ether exposure produced a significant elevation in plasma corticosterone

Miriam Sterman Dolnikoff; Claudio Elias Kater; Mizue Egami; Iracema Senna de Andrade; Maria Regina Marmo



UCLA study finds survival significantly increased in early breast cancer after treatment with Herceptin and chemotherapy:

Treating women with early stage breast cancer with a combination of chemotherapy and the molecularly targeted drug Herceptin significantly increases survival in patients with a specific genetic mutation that results in very aggressive disease, a researcher with UCLA’s Jonsson Comprehensive Cancer Center reported Wednesday.


Increases in Parent Attendance to Behavioral Parent Training Due to Concurrent Child Treatment Groups  

ERIC Educational Resources Information Center

Though behavioral parent training has been demonstrated to be an effective intervention for child behavior problems, it continues to suffer from high attrition rates. Few variables have been found to predict or decrease high attrition rates from parent training classes. The present study found 43-52% increases in attendance rates for parents whose…

Jensen, Scott A.; Grimes, Lisa K.



Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates  

PubMed Central

With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage ?X174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal. PMID:24527627

Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn




SciTech Connect

The Defense Waste Processing Facility (DWPF) has transitioned from Sludge Batch 5 (SB5) processing to Sludge Batch 6 (SB6) processing. Phase III-Tank 40 Chemical Process Cell (CPC) flowsheet simulations have been completed to determine the initial processing conditions for the DWPF transition. The impact of higher yield stress (SB-25) and cycle time extension (SB6-26) on the physical and chemical effects of SB6 processing during the SRAT (Sludge Receipt and Adjustment Tank) cycle were evaluated. No significant impacts on the SRAT chemistry were noted during the higher yield stress run. In particular, no impact on mercury stripping was noted, indicating that settling of elemental mercury was not the primary factor in the low mercury recovery noted in the flowsheet testing. The SRAT product from this run retained the higher yield stress of the starting sludge. The run indicated that ultrasonication is an effective tool to increase the yield stress of simulants to targeted values and the chemistry of downstream processing is not impacted. Significant differences were noted in the cycle time extension test compared to the Phase III flowsheet baseline runs. Large decreases in the ammonia and hydrogen generation rates were noted along with reduced mercury stripping efficiency. The latter effect is similar to that of operating under a high acid stoichiometry. It is conceivable that, under the distinctly different conditions of high formic acid concentration (high acid run) or slow formic acid addition (extended run), that mercury could form amalgams with noble metals, possibly rendering both inert. Thus, the removal of free mercury and noble metals could decrease the rate of catalytic formic acid reactions which would decrease generation of ammonium and hydrogen. The potential underlying reasons for the behavior noted during this run would require additional testing.

Fernandez, A.



Hydrothermal treatment coupled with mechanical expression at increased temperature for excess sludge dewatering: the dewatering performance and the characteristics of products.  


Hydrothermal treatment coupled with mechanical expression at increased temperature in two separate cells respectively is effective for the dewatering of excess sludge with low energy consumption. The objectives of this study were to evaluate the dewatering performance and the characteristics of obtained products (hydrothermal sludge, hydrochar and filtrate). The results showed that harsher hydrothermal treatment (temperature from 120 to 210 °C and residence time from 10 to 90 min) led to greater water removal (from 7.44 to 96.64% reduction of total water) and mechanical pressure became less significant as it increased. The whole expression stage was completely described by the modified Terzaghi-Voigt rheological model. The role of tertiary consolidation stage in the water removal was reduced with hydrothermal treatment being stronger. The hydrothermal treatment is mainly a devolatilization process. The observed changes in H/C and O/C for hydrothermal sludge suggested dehydration was the major reaction mechanism and decarboxylation only occurred significantly at higher temperature. The higher heating value correlated well with carbon content of sludge, which was increased by 4.8% for hydrothermal sludge at 210 °C for 60 min and significantly decreased by 15.4% for hydrochar after 6.0 MPa for 20 min. The solubilization and decomposition of proteins, polysaccharides and DNA were determined to be temperature and residence time dependent. The improvement of dewaterability was closely correlated to the variation of these biopolymers. The filtrates collected above 150 °C were found to be acidic. The increase of humic substances and the melanoidins formed by Maillard reaction were largely responsible for the filtrate color. PMID:25462737

Wang, Liping; Li, Aimin



Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury  

PubMed Central

Background We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated if oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. Methods At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. Results Protein kinetics in leg muscle were expressed in nmol/min/100 ml leg volume (mean±SE). During AA infusion, rates of protein synthesis in leg muscle were increased (p < .05) in both groups (Basal vs. AA: control, 51±8 vs. 86±21; oxandrolone, 56±7 vs. 96±12). In the control group, there was also a simultaneous increase in breakdown (Basal vs. AA: 65±10 vs. 89±25), which resulted in no change in the net balance of leg muscle protein (Basal vs. AA: ? 15±4 vs. ? 2±10). In the oxandrolone group, protein breakdown did not change (Basal vs. AA: 80±12 vs. 77±9), leading to increased net balance (Basal vs. AA: ? 24±7 vs. 19±7, p < .05). Protein breakdown at the whole-body level was not different between the groups. Conclusion Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown. PMID:21333314

Tuvdendorj, D.; Chinkes, DL.; Zhang, XJ.; Suman, OE.; Aarsland, A.; Ferrando, A.; Kulp, GA; Jeschke, MG.; Wolfe, RR.; Herndon, DN.



Phenelzine treatment increases transcription factor AP2 levels in rat brain  

Microsoft Academic Search

BACKGROUND: The elevations of noradrenaline (NA) and serotonin (5-HT) levels in response to acute serotonin reuptake inhibitor (SSRI) or tricyclic antidepressant (TCA) exposure are not consistent with the time course for the therapeutic action of these antidepressants. Thus, neuronal adaptations are needed for the therapeutic effect to arise. Transcription factor Activating Protein –2 (AP-2) is critical for mammalian neural gene

Mattias Damberg; Cecilia Berggård; Lars Oreland



Real-time supervision of industrial waste-water treatment plants applied to the surface treatment industries  

Microsoft Academic Search

The project described in this paper consists of two main stages: the development of a dedicated instrument enabling continuous simultaneous measures of industrial pollutants (e.g. metal ions: Ni2+, Cu2+, Zn2+, …) and the design of a Real-time Expert System (RTES) which would provide better information and decision support so as to improve the supervision of waste-water treatment plants in real-time,

Konrad Szafnicki; Jacques Bourgois; Didier Graillot; Dominique Di Benedetto; Philippe Breuil; Jean-Pierre Poyet



Hydrogen Sulfide Treatment Promotes Glucose Uptake by Increasing Insulin Receptor Sensitivity and Ameliorates Kidney Lesions in Type 2 Diabetes  

PubMed Central

Abstract Aims: To examine if hydrogen sulfide (H2S) can promote glucose uptake and provide amelioration in type 2 diabetes. Results: Treatment with sodium hydrosulfide (NaHS, an H2S donor) increased glucose uptake in both myotubes and adipocytes. The H2S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30??mol·kg?1·day?1) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H2S-generating enzyme cystathionine ?-lyase in the presence or absence of exogenous H2S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. Innovation and Conclusion: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H2S in the both in vitro and in vivo models of insulin resistance. Rebound Track: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Jin-Song Bian, Samuel Dudley, Hideo Kimura, and Xian Wang. Antioxid. Redox Signal. 19, 5–23. PMID:23293908

Xue, Rong; Hao, Dan-Dan; Sun, Ji-Ping; Li, Wen-Wen; Zhao, Man-Man; Li, Xing-Hui; Chen, Ying; Zhu, Jian-Hua; Ding, Ying-Jiong; Liu, Jun



Fivefold confinement time increase in the Madison Symmetric Torus using inductive poloidal current drive  

SciTech Connect

Current profile control is employed in the Madison Symmetric Torus [R. N. Dexter {ital et al.}, Fusion Technol. {bold 19}, 131 (1991)] reversed field pinch to reduce the magnetic fluctuations responsible for anomalous transport. An inductive poloidal electric-field pulse is applied in the sense to flatten the parallel current profile, reducing the dynamo fluctuation amplitude required to sustain the equilibrium. This technique demonstrates a substantial reduction in fluctuation amplitude (as much as 50{percent}), and improvement in energy confinement (from 1 to 5 ms); a record low fluctuation (0.8{percent}) and record high temperature (615 eV) for this device were observed simultaneously during current drive experiments. Plasma beta increases by 50{percent} and the Ohmic input power is three times lower. Particle confinement improves and plasma impurity contamination is reduced. The results of the transient current drive experiments provide motivation for continuing development of steady-state current profile control strategies for the reversed field pinch. {copyright} {ital 1997 American Institute of Physics.}

Stoneking, M.R.; Lanier, N.E.; Prager, S.C.; Sarff, J.S.; Sinitsyn, D. [Department of Physics, University of Wisconsin---Madison, Madison, Wisconsin 53706 (United States)] [Department of Physics, University of Wisconsin---Madison, Madison, Wisconsin 53706 (United States)



In vivo treatment by diallyl disulfide increases histone acetylation in rat colonocytes  

SciTech Connect

Diallyl disulfide (DADS) is an organosulfur compound from garlic which exhibits various anticarcinogenic properties including inhibition of tumor cell proliferation. DADS antiproliferative effects were previously associated with an increase in histone acetylation in two human tumor colon cell lines, suggesting that DADS-induced histone hyperacetylation could be one of the mechanisms involved in its protective properties on colon carcinogenesis. The effects of DADS on histone H4 and H3 acetylation levels were investigated in vivo in colonocytes isolated from non-tumoral rat. Administrated by intracaecal perfusion or gavage, DADS increases histone H4 and H3 acetylation in colonocytes. Moreover, data generated using cDNA expression arrays suggest that DADS could modulate the expression of a subset of genes. These results suggest the involvement of histone acetylation in modulation of gene expression by DADS in normal rat colonocytes, which might play a role in its biological effects as well as in its anticarcinogenic properties in vivo.

Druesne-Pecollo, Nathalie [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France)]. E-mail:; Chaumontet, Catherine [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Pagniez, Anthony [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Vaugelade, Pierre [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Bruneau, Aurelia [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Thomas, Muriel [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Cherbuy, Claire [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Duee, Pierre-Henri [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France); Martel, Paule [Laboratoire de Nutrition et Securite Alimentaire, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas cedex (France)



Stated Briefly: What Does the Research Say about Increased Learning Time and Student Outcomes? REL 2015-061  

ERIC Educational Resources Information Center

REL Appalachia conducted a systematic review of the research evidence on the effects of increased learning time. After screening more than 7,000 studies, REL Appalachia identified 30 that met the most rigorous standards for research. A review of those 30 studies found that increased learning time does not always produce positive results. However,…

Kidron, Yael; Lindsay, Jim



Increased allergen production in turnip ( Brassica rapa) by treatments activating defense mechanisms  

Microsoft Academic Search

Background: Practical applications to enhance the productivity of agriculture by using plants with improved resistance to pathogens are expected to increase in the near future. Defense proteins play an important role in pathogen resistance, and some defense-related proteins are significant cross-reacting allergens. For example, cross-allergies are common among patients allergic to natural rubber latex (NRL), which contains many defense-related proteins.

Anna-Riitta Hänninen; Jari H. Mikkola; Nisse Kalkkinen; Kristiina Turjanmaa; Leea Ylitalo; Timo Reunala; Timo Palosuo



Time to 12-month remission and treatment failure for generalised and unclassified epilepsy  

PubMed Central

Objectives To develop prognostic models for time to 12-month remission and time to treatment failure after initiating antiepileptic drug monotherapy for generalised and unclassified epilepsy. Methods We analysed data from the Standard and New Antiepileptic Drug (arm B) study, a randomised trial that compared initiating treatment with lamotrigine, topiramate and valproate in patients diagnosed with generalised or unclassified epilepsy. Multivariable regression modelling was used to investigate how clinical factors affect the probability of achieving 12-month remission and treatment failure. Results Significant factors in the multivariable model for time to 12-month remission were having a relative with epilepsy, neurological insult, total number of tonic-clonic seizures before randomisation, seizure type and treatment. Significant factors in the multivariable model for time to treatment failure were treatment history (antiepileptic drug treatment prior to randomisation), EEG result, seizure type and treatment. Conclusions The models described within this paper can be used to identify patients most likely to achieve 12-month remission and most likely to have treatment failure, aiding individual patient risk stratification and the design and analysis of future epilepsy trials. PMID:24292995

Bonnett, Laura J; Tudur Smith, Catrin; Smith, David; Williamson, Paula R; Chadwick, David; Marson, Anthony G



Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules  

PubMed Central

In host and cancer tissues, drug metabolism and susceptibility to drugs vary in a circadian (24 h) manner. In particular, the efficacy of a cell cycle specific (CCS) cytotoxic agent is affected by the daily modulation of cell cycle activity in the target tissues. Anti-cancer chronotherapy, in which treatments are administered at a particular time each day, aims at exploiting these biological rhythms to reduce toxicity and improve efficacy of the treatment. The circadian status, which is the timing of physiological and behavioral activity relative to daily environmental cues, largely determines the best timing of treatments. However, the influence of variations in tumor kinetics has not been considered in determining appropriate treatment schedules. We used a simple model for cell populations under chronomodulated treatment to identify which biological parameters are important for the successful design of a chronotherapy strategy. We show that the duration of the phase of the cell cycle targeted by the treatment and the cell proliferation rate are crucial in determining the best times to administer CCS drugs. Thus, optimal treatment times depend not only on the circadian status of the patient but also on the cell cycle kinetics of the tumor. Then, we developed a theoretical analysis of treatment outcome (TATO) to relate the circadian status and cell cycle kinetic parameters to the treatment outcomes. We show that the best and the worst CCS drug administration schedules are those with 24 h intervals, implying that 24 h chronomodulated treatments can be ineffective or even harmful if administered at wrong circadian times. We show that for certain tumors, administration times at intervals different from 24 h may reduce these risks without compromising overall efficacy. PMID:20333244

Bernard, Samuel; ?ajavec Bernard, Branka; Lévi, Francis; Herzel, Hanspeter



Increased mitochondrial superoxide production in rat liver mitochondria, rat hepatocytes, and HepG2 cells following ethinyl estradiol treatment  

Microsoft Academic Search

Ethinyl estradiol (EE) is a strong promoter of hepatocarcino- genesis. Treatment of rats with EE and other hepatic promoters induces a mitosuppressed state characterized by decreased hepa- tocyte turnover and reduced growth responsiveness. Previously, we identified several nuclear and mitochondrial genome-encoded mitochondrial genes whose transcripts were increased during EE- induced hepatic mitosuppression in rats and in EE-treated HepG2 cells (Chen

Jinqiang Chen; Yunbo Li; Jackie A. Lavigne; Michael A. Trush; James D. Yager



NTBC treatment of the pyomelanogenic Pseudomonas aeruginosa clinical isolate PA1111 inhibits pigment production and increases sensitivity to oxidative stress.  


Pyomelanin is a brown/black extracellular pigment with antioxidant and iron acquisition properties that is produced by a number of different bacteria. Production of pyomelanin in Pseudomonas aeruginosa contributes to increased resistance to oxidative stress and persistence in chronic infections. We demonstrate that pyomelanin production can be inhibited by 2-[2-nitro-4-(trifluoromethyl) benzoyl]-1,3-cyclohexanedione (NTBC). This treatment increases sensitivity of pyomelanogenic P. aeruginosa strains to oxidative stress, without altering the growth rate or resistance to aminoglycosides. As such, NTBC has potential to function as an anti-virulence factor in treating pyomelanogenic bacterial infections. PMID:24801336

Ketelboeter, Laura M; M Ketelboeter, Laura; Potharla, Vishwakanth Y; Y Potharla, Vishwakanth; Bardy, Sonia L; L Bardy, Sonia



Application of artificial neural networks to the real time operation of water treatment plants  

Microsoft Academic Search

The water industry is facing increased pressure to produce higher quality treated water at a lower cost. The efficiency of a treatment process closely relates to the operation of the plant. To improve the operating performance, an artificial neural network (ANN) paradigm has been applied to a water treatment plant. An ANN which is able to learn the non-linear performance

A. Mirsepassi; B. Cathers; H. B. Dharmappa



Increasing and decreasing factors of hope in infertile women with failure in infertility treatment: A phenomenology study  

PubMed Central

Background: Assisted reproductive technology (ART) provide the hope of pregnancy for infertile women, but do not always turn this hope into reality. Objective: The purpose of this study was to explore the lived experience of infertile women from increasing and decreasing factors of hope in infertile women with failure in infertility treatment. Materials and Methods: Using a qualitative research design (Phenomenology study), 23 subjects were selected who had experienced infertility failure visited by gynecologist (Rasekh Infertility center) in 2012. The data were collected through semi structured interviews and analyzed using interpretive research strategies of phenomenology by Collizi's seven-stage method. Results: Totally 96 codes were identified. The data arranged in two categories. The factors decreasing and increasing hope in infertility treatments. Totally 5 themes and 20 sub themes were extracted. The increasing factors which emerged from the data contain "spiritual source", "family interaction and support" and "information through the media", and decreasing factors contain "nature of treatments" and "negatively oriented mind". PMID:24799869

Mosalanejad, Leili; Parandavar, Nehle; Gholami, Morteza; Abdollahifard, Sareh



Competition for water at feeding time—The effect of increasing number of individuals per water dispenser  

Microsoft Academic Search

The aim of this study was to study the competition for water at feeding time by increasing number of individuals per nipple drinker (7.5, 15 or 30 goats per nipple) with regard to physical displacements from the nipple drinker, queuing, drinking time, drinking frequency and time per drinking bout. A group of 30 dry and pregnant dairy goats were exposed

Rebecca Ehrlenbruch; Trude Pollen; Inger Lise Andersen; Knut Egil Bøe



Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function  

PubMed Central

Background Hemorrhagic shock is a leading cause of death following severe trauma and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation. Materials and methods Platelet donations were collected from healthy donors (n=5), and stored in gas permeable collection bags according to American Association of Blood Bank recommendations. Platelet units were sampled from day of collection (day 0) until day 7. High resolution respirometry was used to assess baseline mitochondrial respiration, maximal oxygen utilization, and individual mitochondrial complex-dependent respiration. FACS was performed to analyze mitochondrial content, mitochondrial reactive oxygen species (ROS), the expression of P-selectin (both before and after challenge with thrombin receptor activating peptide (SFLLRN)), and apoptosis. Data was analyzed using ANOVA and Pearson’s correlation (p<0.05 significant). Results Mitochondrial respiration decreased significantly in platelets stored longer than 2 days (p<0.05). Platelets also demonstrated a persistent decrease in response to stimulation with SFLLRN by the 3rd day of storage (p<0.05) as well as an increase in mitochondrial ROS and apoptosis (p<0.05). Mitochondrial respiration significantly correlated with platelet capacity to activate (r=0.8, p<0.05). Conclusion Platelet mitochondrial respiratory function and activation response decrease significantly in platelets stored for 3 or more days. Because platelet transfusions almost universally occur between the 3rd and 5th day of storage, our findings may have significant clinical importance and warrant further in vivo analysis. PMID:23830370

Villarroel, José Paul Perales; Figueredo, Ronald; Guan, Yuxia; Tomaiuolo, Maurizio; Karamercan, Mehmet A.; Welsh, John; Selak, Mary A.; Becker, Lance B.; Sims, Carrie



Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy  

PubMed Central

The mechanisms by which valproate, one of the most widely prescribed anti-epileptic drugs, suppresses seizures have not been fully elucidated but may involve up-regulation of neuropeptide Y (NPY). We investigated the effects of valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on brain NPY mRNA expression and seizure control. GAERS were administered either valproate (42 hr?1) or saline continuously for 5 days. Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and the percentage of time spent in seizure activity was analysed. NPY mRNA expression was measured in different brain regions using qPCR. Valproate treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA expression in the thalamus (p<0.05) compared to saline treatment. These results demonstrate that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by which valproate suppresses absence seizures. PMID:24039965

van Raay, Leena; Dedeurwaerdere, Stefanie; O’Brien, Terence J.; Morris, Margaret J.



Additional highway capacity gained by increasing travel speed affects the share of time an individual  

E-print Network

travel time enables people to achieve greater satisfaction from con- sumption, change to a better job to highway expansion will give individuals more time to spend engaged in different activities. Travel

Levinson, David M.


Reaching the London Declaration on Neglected Tropical Diseases Goals for Onchocerciasis: An Economic Evaluation of Increasing the Frequency of Ivermectin Treatment in Africa  

PubMed Central

Background.?Recently, there has been a shift in onchocerciasis control policy, changing from prevention of morbidity toward elimination of infection. Switching from annual to biannual ivermectin distribution may accelerate progress toward the elimination goals. However, the settings where this strategy would be cost effective in Africa have not been described. Methods.?An onchocerciasis transmission framework (EpiOncho) was coupled to a disease model in order to explore the impact on disability-adjusted life years averted, program cost, and program duration of biannual ivermectin treatment in different epidemiological and programmatic scenarios in African savannah. Results.?While biannual treatment yields only small additional health gains, its benefit is pronounced in the context of the elimination goals, shortening the time frames for and increasing the feasibility of reaching the proposed operational thresholds for stopping treatment. In settings with high precontrol endemicity (and/or poor coverage and compliance), it may not be possible to reach such thresholds even within 50 years of annual ivermectin, requiring adoption of biannual treatment. Our projections highlight the crucial role played by coverage and compliance in achieving the elimination goals. Conclusions.?Biannual ivermectin treatment improves the chances of reaching the 2020/2025 elimination goals, potentially generating programmatic cost savings in settings with high precontrol endemicity. However, its benefit and cost are highly sensitive to levels of systematic noncompliance and, in many settings, it will lead to an increase in costs. Furthermore, it may not always be feasible to implement biannual treatment, particularly in hard-to-reach populations. This highlights the continued need for a macrofilaricide. PMID:24944228

Turner, Hugo C.; Walker, Martin; Churcher, Thomas S.; Osei-Atweneboana, Mike Y.; Biritwum, Nana-Kwadwo; Hopkins, Adrian; Prichard, Roger K.; Basáñez, María-Gloria



Accounting for heterogeneity among treatment sites and time trends in developing crash modification functions.  


Collision modification factors (CMFs) are commonly used to quantify the impact of safety countermeasures. The CMFs obtained from observational before-after (BA) studies are usually estimated by averaging the safety impact (i.e., index of effectiveness) for a group of treatment sites. The heterogeneity among the treatment locations, in terms of their characteristics, and the effect of this heterogeneity on safety treatment effectiveness are usually ignored. This is in contrast to treatment evaluations in other fields like medical statistics where variations in the magnitude (or in the direction) of response to the same treatment given to different patients are considered. This paper introduces an approach for estimating a CMFunction from BA safety studies that account for variable treatment location characteristics (heterogeneity). The treatment sites heterogeneity was incorporated into the CMFunction using fixed-effects and random-effects regression models. In addition to heterogeneity, the paper also advocates the use of CMFunctions with a time variable to acknowledge that the safety treatment (intervention) effects do not occur instantaneously but are spread over future time. This is achieved using non-linear intervention (Koyck) models, developed within a hierarchical full Bayes (FB) context. To demonstrate the approach, a case study is presented to evaluate the safety effectiveness of the "Signal Head Upgrade Program" recently implemented in the city of Surrey (British Columbia, Canada), where signal visibility was improved at several urban signalized intersections. The results demonstrated the importance of considering treatment sites heterogeneity and time trends when developing CMFunctions. PMID:25033279

Sacchi, Emanuele; Sayed, Tarek



Increasing Personal and Organizational Effectiveness. Treatise No. 4: "Time Management Techniques."  

ERIC Educational Resources Information Center

The ways in which time is utilized can be enhanced through careful management. The time to be allocated to various activities and objectives should be planned on a weekly basis in light of consciously set priorities. Commonly used but rarely useful strategies for time management include working faster and working longer, both of which lead to…

New Mexico Research and Study Council, Albuquerque.


A Prospective, Randomized Clinical Investigation of the Treatment of First-Time Ankle Sprains  

Microsoft Academic Search

Background: Acute ankle ligament sprains are treated with the use of controlled mobilization with protection provided by external support (eg, functional treatment); however, there is little information regarding the best type of external support to use.Hypothesis: There is no difference between elastic wrapping, bracing, bracing combined with elastic wrapping, and casting for treatment of acute, first-time ankle ligament sprains in

Bruce D. Beynnon; Per A. Renström; Larry Haugh; Benjamin S. Uh; Howard Barker



Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy.  


Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations. PMID:25904800

Hawkins-Salsbury, Jacqueline A; Shea, Lauren; Jiang, Xuntian; Hunter, Daniel A; Guzman, A Miguel; Reddy, Adarsh S; Qin, Elizabeth Y; Li, Yedda; Gray, Steven J; Ory, Daniel S; Sands, Mark S



Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy.  


Epilepsy is one of the most common and intractable brain disorders. Mutations in the human gene LGI1, encoding a neuronal secreted protein, cause autosomal dominant lateral temporal lobe epilepsy (ADLTE). However, the pathogenic mechanisms of LGI1 mutations remain unclear. We classified 22 reported LGI1 missense mutations as either secretion defective or secretion competent, and we generated and analyzed two mouse models of ADLTE encoding mutant proteins representative of the two groups. The secretion-defective LGI1(E383A) protein was recognized by the ER quality-control machinery and prematurely degraded, whereas the secretable LGI1(S473L) protein abnormally dimerized and was selectively defective in binding to one of its receptors, ADAM22. Both mutations caused a loss of function, compromising intracellular trafficking or ligand activity of LGI1 and converging on reduced synaptic LGI1-ADAM22 interaction. A chemical corrector, 4-phenylbutyrate (4PBA), restored LGI1(E383A) folding and binding to ADAM22 and ameliorated the increased seizure susceptibility of the LGI1(E383A) model mice. This study establishes LGI1-related epilepsy as a conformational disease and suggests new therapeutic options for human epilepsy. PMID:25485908

Yokoi, Norihiko; Fukata, Yuko; Kase, Daisuke; Miyazaki, Taisuke; Jaegle, Martine; Ohkawa, Toshika; Takahashi, Naoki; Iwanari, Hiroko; Mochizuki, Yasuhiro; Hamakubo, Takao; Imoto, Keiji; Meijer, Dies; Watanabe, Masahiko; Fukata, Masaki



Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis  

SciTech Connect

Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

Singh, Anurag K., E-mail: Anurag.singh@roswellpark.or [Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York (United States); Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno [Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York (United States)




Technology Transfer Automated Retrieval System (TEKTRAN)

With rising energy costs, fuel-consumptive soil management practices, such as deep tillage, need to be reassessed to determine whether they need to be performed every year or not. Between 1978 and 1996, conservation (non-disked) and conventional (disked) tillage treatments had been annually deep til...


Investigation of Pitch and Jaw Width to Decrease Delivery Time of Helical Tomotherapy Treatments for Head and Neck Cancer  

SciTech Connect

Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 {+-} 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 {+-} 0.6 min vs. 9.5 {+-} 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

Moldovan, Monica [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Fontenot, Jonas D., E-mail: [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Gibbons, John P. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Lee, Tae Kyu [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Rosen, Isaac I. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Fields, Robert S. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Hogstrom, Kenneth R. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States)



Increase in cone biomass and terpenophenolics in hops ( Humulus lupulus L.) by treatment with prohexadione-calcium.  


Humulus lupulus L. (hop), a specialty crop bred for flavor characteristics of the inflorescence, is an essential ingredient in beer. Hop inflorescences, commonly known as hop cones, contain terpenophenolic compounds, which are important for beer flavoring and of interest in biomedical research. Hop breeders focus their efforts on increasing cone biomass and terpenophenolic content. As an alternative to traditional breeding, hops were treated with prohexadione-calcium (Pro-Ca), a growth inhibitor previously shown to have positive agronomic effects in several crops. Application of Pro-Ca to hop plants during cone maturation induced increases in cone biomass production by 1.5-19.6% and increased terpenophenolic content by 9.1-87.3%; however, some treatments also induced significant decreases in terpenophenolic content. Induced changes in cone biomass production and terpenophenolic accumulation were most dependent on cultivar and the developmental stage at which plants were treated. PMID:21598976

Kavalier, Adam R; Pitra, Nicholi J; Koelling, Jared M; Coles, Mark C; Kennelly, Edward J; Matthews, Paul D



Effects on alcohol related fatal crashes of a community based initiative to increase substance abuse treatment and reduce alcohol availability  

PubMed Central

Objective: This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. Intervention: Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. Design: A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. Main outcome measures: The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. Results: Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. Conclusions: Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes. PMID:15805436

Hingson, R; Zakocs, R; Heeren, T; Winter, M; Rosenbloom, D; DeJong, W



It's about Time! Increasing the Length of Student Classroom Writing without Setting Length Constraints.  

ERIC Educational Resources Information Center

This paper grew out of the collaborative relationship that emerged from in-class modeling of student-centered writing approaches as participating teachers and a consultant/researcher began to explore ways to increase the length of fourth-grade writing. The paper reports on a small study in fourth-grade writing aimed at increasing the length of…

Passman, Roger


Real-time fault detection and isolation in biological wastewater treatment plants.  


Automatic fault detection is becoming increasingly important in wastewater treatment plant operation, given the stringent treatment standards and the need to protect the investment costs from the potential damage of an unchecked fault propagating through the plant. This paper describes the development of a real-time Fault Detection and Isolation (FDI) system based on an adaptive Principal Component Analysis (PCA) algorithm, used to compare the current plant operation with a correct performance model based on a reference data set and the output of three ion-specific sensors (Hach-Lange gmbh, Düsseldorf, Germany): two Nitratax NOx UV sensors, in the denitrification tank and downstream of the oxidation tanks, where an Amtax ammonium-N sensor was also installed. The algorithm was initially developed in the Matlab environment and then ported into the LabView 8.20 (National Instruments, Austin, TX, USA) platform for real-time operation using a compact Field Point, a Programmable Automation Controller by National Instruments. The FDI was tested with a large set of operational data with 1 min sampling time from August 2007 through May 2008 from a full-scale plant. After describing the real-time version of the PCA algorithm, this was tested with nine months of operational data which were sequentially processes by the algorithm in order to simulate an on-line operation. The FDI performance was assessed by organizing the sequential data in two differing moving windows: a short-horizon window to test the response to single malfunctions and a longer time-horizon to simulate multiple unrepaired failures. In both cases the algorithm performance was very satisfactory, with a 100% failure detection in the short window case, which decreased to 84% in the long window setting. The short-window performance was very effective in isolating sensor failures and short duration disturbances such as spikes, whereas the long term horizon provided accurate detection of long-term drifts and proved robust enough to allow for some delay in failure recovery. The system robustness is based on the use of multiple statistics which proved instrumental in discriminating among the various causes of malfunctioning. PMID:19934517

Baggiani, F; Marsili-Libelli, S



Increased Learning Time and Targeted Instruction Improve Academic Skills for At-Risk ESL Learners  

ERIC Educational Resources Information Center

Students with English as a Second Language (ESL) face two critical challenges: they need to develop English literacy while, at the same time, acquire content knowledge across subject areas. These students need a targeted ESL curriculum from elementary to high school that will allow an extended learning time and opportunities to practice as they…

Nelson, April, Comp.



A Response to Uncertainty: The Increased Utilization of Part-Time Instructors in American Community Colleges.  

ERIC Educational Resources Information Center

Reviews research on the use of part-time faculty in community colleges, focusing on employment trends; impacts and concerns; economic advantages; the effects of funding uncertainty; part-time faculty members' expertise, instructional quality, socialization, and selection; standardization of process and teaching skills; and implications for…

Boggs, George R.



Increase in pyrolytic carbon optical anisotropy and density during processing of coated particle fuel due to heat treatment  

SciTech Connect

Measurements of pyrolytic carbon optical anisotropy and density have been made on a series of tri-isotropic (TRISO) coated particles prepared for the United States Department of Energy's Advanced Gas Reactor Fuel Development and Qualification (AGR) program. These measurements show the effect of varying the deposition conditions, especially the deposition temperature, on the density and optical anisotropy of the carbon layers. Additional heat treatment studies of the coated particles at various stages illustrate the strong effect of post-deposition thermal processing on these two pyrolytic carbon properties. Such post-deposition heat treatment occurs during SiC deposition and fuel compact firing, resulting in a microstructural modification of the pyrolytic carbon which increases the anisotropy and density of these layers.

Hunn, John D [ORNL; Jellison Jr, Gerald Earle [ORNL; Lowden, Richard Andrew [ORNL



Enhancing the efficiency of gold nanoparticles treatment of cancer by increasing their rate of endocytosis and cell accumulation using rifampicin.  


To minimize the toxicity of gold nanoparticles (AuNPs) in cancer treatment, we have developed a technique, which utilizes lesser amount of AuNPs while exhibiting increased treatment efficiency. Rifampicin (RF) is known for its ability to enhance the accumulation of anticancer drugs in multidrug resistant (MDR) cancer cells. In this work we have shown that RF-conjugated AuNPs can greatly enhance the rate as well as efficiency of endocytosis of NPs and hence their concentration inside the cancer cell. Cell viability results showed a remarkable enhancement in the photothermal therapeutic effect of Au nanorods in presence of RF. This is expected to decrease the demand on the overall amount of AuNPs needed for treating cancer and thus decreasing its toxicity. PMID:24467386

Ali, Moustafa R K; Panikkanvalappil, Sajanlal R; El-Sayed, Mostafa A



Accounting for individual differences and timing of events: estimating the effect of treatment on criminal convictions in heroin users  

PubMed Central

Background The reduction of crime is an important outcome of opioid maintenance treatment (OMT). Criminal intensity and treatment regimes vary among OMT patients, but this is rarely adjusted for in statistical analyses, which tend to focus on cohort incidence rates and rate ratios. The purpose of this work was to estimate the relationship between treatment and criminal convictions among OMT patients, adjusting for individual covariate information and timing of events, fitting time-to-event regression models of increasing complexity. Methods National criminal records were cross linked with treatment data on 3221 patients starting OMT in Norway 1997–2003. In addition to calculating cohort incidence rates, criminal convictions was modelled as a recurrent event dependent variable, and treatment a time-dependent covariate, in Cox proportional hazards, Aalen’s additive hazards, and semi-parametric additive hazards regression models. Both fixed and dynamic covariates were included. Results During OMT, the number of days with criminal convictions for the cohort as a whole was 61% lower than when not in treatment. OMT was associated with reduced number of days with criminal convictions in all time-to-event regression models, but the hazard ratio (95% CI) was strongly attenuated when adjusting for covariates; from 0.40 (0.35, 0.45) in a univariate model to 0.79 (0.72, 0.87) in a fully adjusted model. The hazard was lower for females and decreasing with older age, while increasing with high numbers of criminal convictions prior to application to OMT (all p?time-varying with their effects diminishing over time. Conclusions Analyzing complex observational data regarding to fixed factors only overlooks important temporal information, and naïve cohort level incidence rates might result in biased estimates of the effect of interventions. Applying time-to-event regression models, properly adjusting for individual covariate information and timing of various events, allows for more precise and reliable effect estimates, as well as painting a more nuanced picture that can aid health care professionals and policy makers. PMID:24886472



Simulated Changes in the Asian Summer Monsoon at Times of Increased Atmospheric CO2  

Microsoft Academic Search

Possible changes in the Asian summer monsoon due to increased atmospheric CO2 are investigated by an MRI global coupled atmosphere-ocean general circulation model. The summer (June-August) monsoon rainfall in India increases significantly with global warming. On the other hand, the monsoon wind shear index, defined as the difference between 850hPa and 200hPa zonal winds over the northern Indian Ocean, decreases.

Akio Kitoh; Seiji Yukimoto; A. Noda; Tatsuo Motoi



Infrared detector Dewars - Increased LN2 hold time and vacuum jacket life spans  

NASA Technical Reports Server (NTRS)

IR detector Dewars commonly suffer from shorter than desired LN2 hold times and insulation jacket vacuum corruption over relatively short time periods. In an attempt to solve this problem for a 9144 detector Dewar, small 1 liter/s appendage ion pumps were selected for continuous pumping of the vacuum jackets. This procedure extended LN2 hold times from 20 to 60 h and virtually eliminated vacuum jacket corruption. Thus the detector systems are usable continuously over periods of 6 months or more.

Jennings, D. E.; Boyd, W. J.; Blass, W. E.



The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.  


The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed. PMID:25025529

Alén, Francisco; Serrano, Antonia; Gorriti, Miguel Ángel; Pavón, Francisco Javier; Orio, Laura; de Heras, Raquel Gómez; Ramírez-López, María Teresa; Antón, María; Pozo, Miguel Ángel; Rodríguez de Fonseca, Fernando



Sleep Restriction Therapy for Insomnia is Associated with Reduced Objective Total Sleep Time, Increased Daytime Somnolence, and Objectively Impaired Vigilance: Implications for the Clinical Management of Insomnia Disorder  

PubMed Central

Study Objectives: To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Design: Within-subject, noncontrolled treatment investigation. Setting: Sleep research laboratory. Participants: Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ? 6 h. Interventions: Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Measurement and results: Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). Conclusion: For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia. Citation: Kyle SD; Miller CB; Rogers Z; Siriwardena AN; MacMahon KM; Espie CA. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. SLEEP 2014;37(2):229-237. PMID:24497651

Kyle, Simon D.; Miller, Christopher B.; Rogers, Zoe; Siriwardena, A. Niroshan; MacMahon, Kenneth M.; Espie, Colin A.



Effects of drought and warming treatments on CO2 fluxes in shrubland ecosystems across an environmental gradient: a synthesis of the INCREASE project  

NASA Astrophysics Data System (ADS)

Seasonal changes of net ecosystem exchange (NEE) of terrestrial ecosystems are the result of different interactions between CO2 assimilation (GPP) and ecosystem respiration (ER) with environmental drivers. There is still debate about to which extent low soil moisture (drought) and increased temperature (warming) can affect GPP or ER depending on both functional groups and ecosystem climate types. In dynamic systems, such as shrubland ecosystems, these effects can be difficult to predict. We used the INCREASE network infrastructure "space-for-time substitution" (natural gradient and experimental approach) to quantify the effects of drought and warming on GPP, ER, SR and NEE across 6 European shrublands. The sites ranged from Denmark to Southern Italy along a precipitation and temperature gradient. In addition, INCREASE experimentally manipulates the climate in 20 m2 plots simulating the climate change: reflective curtains are drawn across plots at night preventing heat loss (warming treatment) while other plots are periodically covered by curtains during rain events thereby reducing the water input from precipitation (drought treatment). The measurements of soil CO2 efflux (SR), net ecosystem CO2 exchange (NEE) and total ecosystem respiration (ER) were done according to common protocols using chamber method, while the gross ecosystem photosynthesis (GPP) was estimated by difference between NEE and ER. Preliminary results indicate large flux variability across the sites and the seasons. The drought treatment tends to limit the loss of CO2 through the respiratory processes, while the warming treatment seems to stimulate all the processes in most sites, even in the Mediterranean where the temperature has never been considered a limiting factor.

Guidolotti, Gabriele; Steenberg Larsen, Klaus; de Dato, Giovanbattista; Baarsel, Susie; Lellei-Kovács, Eszter; Kopittke, Gillian; Tietema, Albert; Emmet, Bridgett; De Angelis, Paolo; Kappel Schmidt, Inger



Open Lab Time as a Strategy to Increase Female (and Male) Retention  

NSDL National Science Digital Library

This report explains how El Camino College used additional open lab time for their welding and electronics classes to aid all students and especially female students. This is because "female students come to classes with less hands-on experience than their male counterparts." El Camino College also added flexibility to the lab times to allow students who were taking night classes to use the lab.


Capillary Suction Time. Operational Control Tests for Wastewater Treatment Facilities. Instructor's Manual [and] Student Workbook.  

ERIC Educational Resources Information Center

Capillary suction time is time required for the liquid phase of a treated sludge to travel through 1 centimeter of media (blotter or filter paper). Designed for individuals who have completed National Pollutant Discharge Elimination System (NPDES) level 1 laboratory training skills, this module provides waste water treatment plant operators with…

Wooley, John F.


Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.  


The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-?, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP. PMID:24671717

Nakamura, Tatsufumi; Satoh, Katsuya; Fukuda, Taku; Kinoshita, Ikuo; Nishiura, Yoshihiro; Nagasato, Kunihiko; Yamauchi, Atsushi; Kataoka, Yasufumi; Nakamura, Tadahiro; Sasaki, Hitoshi; Kumagai, Kenji; Niwa, Masami; Noguchi, Mitsuru; Nakamura, Hideki; Nishida, Noriyuki; Kawakami, Atsushi



Adderall ® produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers  

Microsoft Academic Search

Rationale  Adderall® is currently used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) and is composed of a novel mixture\\u000a of approximately 24% l-amphetamine and 76% d-amphetamine salts. There are, however, no investigations of the pharmacological effects of this combination in vivo.\\u000a \\u000a \\u000a \\u000a Objectives  The technique of high-speed chronoamperometry using Nafion®-coated single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine (DA) release produced

B. Matthew Joyce; Paul E. A. Glaser; Greg A. Gerhardt



Using a Time Timer[TM] to Increase Appropriate Waiting Behavior in a Child with Developmental Disabilities  

ERIC Educational Resources Information Center

This study aimed to examine the use of a predictive stimulus (Time Timer[TM]) and delayed reinforcement to increase appropriate waiting behavior in a child with developmental disabilities and problem behavior maintained by access to tangible items and activities. The study employed a changing criterion design across settings to gradually increase

Grey, Ian; Healy, Olive; Leader, Geraldine; Hayes, Deirdre



Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness  

PubMed Central

Background: Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing–remitting MS patients showed a clinically meaningful decrease in fatigue over 1?year of treatment with natalizumab. Objective: To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness. Methods: Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed. Results: After 1?year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue. Conclusion: Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression. PMID:25755648

Penner, Iris-Katharina; Sivertsdotter, Eva Catharina; Celius, Elisabeth G.; Fuchs, Siegrid; Schreiber, Karen; Berkö, Sara; Svenningsson, Anders




PubMed Central

Certain axonal membranes of crayfish abdominal nerve cord display ultrastructural changes if the axons are fixed, during electrical stimulation, by aldehydes followed by osmium. Such changes are characterized by an increase in electron opacity and thickness of the unit membranes' dense strata in the axon surface, endoplasmic reticulum, and outer mitochondrial membranes. The electron opacity completely disappears if the sections are treated with hydrogen peroxide solutions. This suggests that the changes represent an increase in the membranes' reactivity for osmium. An unmasking of SH groups could explain such increased osmiophilia, since SH groups are very reactive with osmium, while disulfide bonds are considerably less reactive. This hypothesis was tested by treating control, glutaraldehydefixed nerve cords with disulfide reducing agents. In these preparations an increase in electron opacity and thickness was observed to be localized in the same axonal membranes which reacted as a result of electrical stimulation. The phenomenon did not appear if the SH groups were blocked by maleimide or N-ethylmaleimide before treatment with osmium. These findings seem to suggest that certain axonal membranes of crayfish contain proteins rich in sulfur whose SH groups are unmasked as a result of electrical stimulation. In preliminary experiments an increase in osmiophilia localized in the same membranes with the same characteristics and distribution was observed also in axons from nerve cords asphyxiated either in vitro or in the living animal. PMID:5111876

Peracchia, Camillo; Robertson, J. David



Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance  

PubMed Central

The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection. PMID:25110421

Smith, Sinéad M; O’Morain, Colm; McNamara, Deirdre



Salivary oxytocin increases concurrently with testosterone and time away from home among returning Tsimane' hunters.  


Oxytocin, testosterone and cortisol can have opposing effects on social behaviour, yet few studies have examined their interactions. We measured changes in salivary oxytocin, testosterone and cortisol among Tsimane' men returning home after hunting, an ancient context of male status competition, parental investment and cooperation. Contra normal diurnal rhythm, oxytocin increased relative to baseline and this increase was positively associated with duration of the hunt and change in testosterone, but not cortisol, social context, hunting outcome or physical activity. The concurrent increase in endogenous peripheral oxytocin and testosterone is unexpected given their opposing independent effects on social cognition and behaviour, and has not been observed before. We discuss the potential significance of these effects for the biology of pair-bonding, parenting and social foraging in humans and other species. PMID:25788487

Jaeggi, Adrian V; Trumble, Benjamin C; Kaplan, Hillard S; Gurven, Michael



Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study  

PubMed Central

Objectives To investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased (“systolic intensification threshold”) and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death. Design Retrospective cohort study. Setting Primary care practices in the United Kingdom, 1986-2010. Participants 88?756 adults with hypertension from The Health Improvement Network nationwide primary care research database. Main outcome measures Rates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure. Results During a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P<0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P<0.001). Conclusions Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension. PMID:25655523

Xu, Wenxin; Goldberg, Saveli I; Shubina, Maria



A Proton Beam Therapy System Dedicated to Spot-Scanning Increases Accuracy with Moving Tumors by Real-Time Imaging and Gating and Reduces Equipment Size  

PubMed Central

Purpose A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation. Materials and Methods In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT). Results With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively. Conclusions This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment. PMID:24747601

Shimizu, Shinichi; Miyamoto, Naoki; Matsuura, Taeko; Fujii, Yusuke; Umezawa, Masumi; Umegaki, Kikuo; Hiramoto, Kazuo; Shirato, Hiroki



Method and computer product to increase accuracy of time-based software verification for sensor networks  


A recursive verification protocol to reduce the time variance due to delays in the network by putting the subject node at most one hop from the verifier node provides for an efficient manner to test wireless sensor nodes. Since the software signatures are time based, recursive testing will give a much cleaner signal for positive verification of the software running on any one node in the sensor network. In this protocol, the main verifier checks its neighbor, who in turn checks its neighbor, and continuing this process until all nodes have been verified. This ensures minimum time delays for the software verification. Should a node fail the test, the software verification downstream is halted until an alternative path (one not including the failed node) is found. Utilizing techniques well known in the art, having a node tested twice, or not at all, can be avoided.

Foo Kune, Denis (Saint Paul, MN); Mahadevan, Karthikeyan (Mountain View, CA)



Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria  

PubMed Central

Summary In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, P. falci-parum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (p=0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasize the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp. PMID:23198734

Lin, Jessica T.; Mbewe, Bernard; Taylor, Steve M.; Luntamo, Mari; Meshnick, Steven R.; Ashorn, Per



Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria.  


In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, Plasmodium falciparum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (P = 0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasise the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp. PMID:23198734

Lin, Jessica T; Mbewe, Bernard; Taylor, Steve M; Luntamo, Mari; Meshnick, Steven R; Ashorn, Per



Increased Nek1 expression in Renal Cell Carcinoma cells is associated with decreased sensitivity to DNA-damaging treatment  

PubMed Central

Renal cell carcinoma (RCC) is a heterogeneous disease with resistance to systemic chemotherapy. Elevated expression of multiple drug resistance (MDR) has been suggested to be one of the mechanisms for this resistance. Here, we provide an alternative mechanism to explain RCC's resistance to chemotherapy-induced apoptosis. Never-in mitosis A-related protein kinase 1 (Nek1) plays an important role in DNA damage response and proper checkpoint activation. The association of Nek1 with the voltage-dependent anion channel (VDAC1) is a critical determinant of cell survival following DNA-damaging treatment. We report here that Nek1 is highly expressed in RCC tumor and cultured RCC cells compared to that of normal renal tubular epithelial cells (RTE). The association between Nek1 and VDAC1 is genotoxic dependent: prolonged Nek1/VDAC1 dissociation will lead to VDAC1 dephosphorylation and initiate apoptosis. Down-regulation of Nek1 expression in RCC cells enhanced their sensitivity to DNA-damaging treatment. Collectively, these results suggest that the increased Nek1 expression in RCC cells maintain persistent VDAC1 phosphorylation, closing its channel and preventing the onset of apoptosis under genotoxic insults. Based on these results, we believe that Nek1 can serve as a potential therapeutic target for drug development in the treatment of RCC. PMID:24970796

Chen, Yumay; Chen, Chi-Fen; Polci, Rosaria; Wei, Randy; Riley, Daniel J.; Chen, Phang-Lang



World population continues to increase, while at the same time, thousands of acres of arable land  

E-print Network

. Technological advances in commerce, healthcare, agriculture and energy production in the 21st Century are lost to development each year, and the result is increased pressure on agriculture/aquaculture to provide affordable, safe, and nutritious foods. New and innovative technologies are being developed


Global Fairness of Additive-Increase and Multiplicative-Decrease with Heterogeneous Round-Trip Times  

Microsoft Academic Search

Consider a network with an arbitrary topology and arbitrary communication delays, in which congestion control is based on additive- increase and multiplicative-decrease. We show that the source rates tend to be distributed in order to maximize an objective function called (\\

Milan Vojnovic; Jean-Yves Le Boudec; Catherine Boutremans



Measuring and Increasing Time-On-Task: A Cost Effective Approach.  

ERIC Educational Resources Information Center

This paper describes Detroit's "Peer Teachers as Mirrors and Monitors" project, a cost effective approach to increasing student achievement in mathematics and reading in grades one through four in Title I schools. The program consists of: (1) an observation/feedback system giving teachers data from their students' engaged-in-learning rates; and…

Moore, JoAnne E.


Less is more: treatment with BTH and laminarin reduces herbivore-induced volatile emissions in maize but increases parasitoid attraction.  


Chemical plant strengtheners find increasing use in agriculture to enhance resistance against pathogens. In an earlier study, it was found that treatment with one such resistance elicitor, BTH (benzo-(1, 2, 3)-thiadiazole-7-carbothioic acid S-methyl ester), increases the attractiveness of maize plants to a parasitic wasp. This surprising additional benefit of treating plants with BTH prompted us to conduct a series of olfactometer tests to find out if BTH and another commercially available plant strengthener, Laminarin, increase the attractiveness of maize to three important parasitic wasps, Cotesia marginventris, Campoletis sonorensis, and Microplitis rufiventris. In each case, plants that were sprayed with the plant strengtheners and subsequently induced to release volatiles by real or mimicked attack by Spodoptera littoralis caterpillars became more attractive to the parasitoids than water treated plants. The elicitors alone or in combination with plants that were not induced by herbivory were not attractive to the wasps. Interestingly, plants treated with the plant strengtheners did not show any consistent increase in volatile emissions. On the contrary, treated plants released less herbivore-induced volatiles, most notably indole, which has been reported to interfere with parasitoid attraction. The emission of the sesquiterpenes (E)-?-caryophyllene, ?-bergamotene, and (E)-?-farnesene was similarly reduced by the treatment. Expression profiles of marker genes showed that BTH and Laminarin induced several pathogenesis related (PR) genes. The results support the notion that, as yet undetectable and unidentified compounds, are of major importance for parasitoid attraction, and that these attractants may be masked by some of the major compounds in the volatile blends. This study confirms that elicitors of pathogen resistance are compatible with the biological control of insect pests and may even help to improve it. PMID:22456950

Sobhy, Islam S; Erb, Matthias; Sarhan, Awad A; El-Husseini, Monir M; Mandour, Nasser S; Turlings, Ted C J



Estimating time-varying effects for overdispersed recurrent events data with treatment switching  

PubMed Central

Summary In the analysis of multivariate event times, frailty models assuming time-independent regression coefficients are often considered, mainly due to their mathematical convenience. In practice, regression coefficients are often time dependent and the temporal effects are of clinical interest. Motivated by a phase III clinical trial in multiple sclerosis, we develop a semiparametric frailty modelling approach to estimate time-varying effects for overdispersed recurrent events data with treatment switching. The proposed model incorporates the treatment switching time in the time-varying coefficients. Theoretical properties of the proposed model are established and an efficient expectation-maximization algorithm is derived to obtain the maximum likelihood estimates. Simulation studies evaluate the numerical performance of the proposed model under various temporal treatment effect curves. The ideas in this paper can also be used for time-varying coefficient frailty models without treatment switching as well as for alternative models when the proportional hazard assumption is violated. A multiple sclerosis dataset is analysed to illustrate our methodology. PMID:24465031




Variable-time reinforcement schedules in the treatment of socially maintained problem behavior  

Microsoft Academic Search

Noncontingent reinforcement (NCR) consists of delivering a reinforcer on a time-based schedule, independent of responding. Studies evaluating the effectiveness of NCR as treatment for problem behavior have used fixed-time (FT) schedules of reinforcement. In this study, the efficacy of NCR with variable-time (VT) schedules was evaluated by comparing the effects of VT and FT reinforcement schedules with 2 individuals who

CAROLE M. VAN CAMP; D C Lerman; M ICHAEL E. KELLEY; S A Contrucci; C M Vorndran



The time-dependent Poisson's ratio of viscoelastic materials can increase or decrease  

E-print Network

foam skeleton (Lakes, 1987) in which microcellular viscoelastic foam with a conventional cell structure. Lakes Cellular Polymers, 11, 466-469, (1992). 1 Summary In viscoelastic materials, the Poisson's ratio domain. Then, (t) = 1 2 - E(t) 6B (3) #12;Time dependent Poisson's ratio, R. S. Lakes, University

Lakes, Roderic


Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.  


The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs. PMID:15565110

Binder, Elisabeth B; Salyakina, Daria; Lichtner, Peter; Wochnik, Gabriele M; Ising, Marcus; Pütz, Benno; Papiol, Sergi; Seaman, Shaun; Lucae, Susanne; Kohli, Martin A; Nickel, Thomas; Künzel, Heike E; Fuchs, Brigitte; Majer, Matthias; Pfennig, Andrea; Kern, Nikola; Brunner, Jürgen; Modell, Sieglinde; Baghai, Thomas; Deiml, Tobias; Zill, Peter; Bondy, Brigitta; Rupprecht, Rainer; Messer, Thomas; Köhnlein, Oliver; Dabitz, Heike; Brückl, Tanja; Müller, Nina; Pfister, Hildegard; Lieb, Roselind; Mueller, Jakob C; Lõhmussaar, Elin; Strom, Tim M; Bettecken, Thomas; Meitinger, Thomas; Uhr, Manfred; Rein, Theo; Holsboer, Florian; Muller-Myhsok, Bertram



Surgical treatment for hydrosalpinx increases the expression of integrin ?v?3 in the endometrium during the implantation window  

PubMed Central

To investigate the clinical importance of increased integrin ?v?3 expression in the endometrium following the surgical treatment for hydrosalpinx, a total of 60 patients with hydrosalpinx and 30 patients with fallopian tube obstruction were recruited. In the implantation window, immunohistochemistry was performed to detect integrin ?v?3 expression in the endometrium of the hydrosalpinx patients before and after surgery and of patients with fallopian tube obstruction. In the implantation window, integrin ?v?3 expression levels in the endometrium of hydrosalpinx patients before surgery were significantly lower compared to those in patients with fallopian tube obstruction (P<0.05). However, there were no marked differences in integrin ?v?3 expression in the implantation window between hydrosalpinx patients after surgical intervention and patients with fallopian tube obstruction (P>0.05). Furthermore, for patients with hydrosalpinx, integrin ?v?3 expression levels in the implantation window were dramatically increased after surgery (P<0.05). Hydrosalpinx decreases integrin ?v?3 expression in the endometrium in the implantation window, and integrin ?v?3 may be an important factor influencing the endometrial receptivity of hydrosalpinx patients. Surgical treatment for hydrosalpinx can improve integrin ?v?3 expression in the endometrium during implantation. PMID:23181110




Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy.  


Diabetic nephropathy (DN) is a serious complication of longstanding diabetes affecting up to 30% of all diabetes patients and is the main cause of end-stage kidney disease globally. Current standard treatment e.g. ACE-inhibitors like enalapril merely offers a delay in the progression leading to DN. Herein, we describe in two preclinical models evidence to local effects on the inflammatory signatures after intervention treatment with enalapril which provides enhanced understanding of the mechanism of ACE inhibitors. Enalapril transiently reduced albuminuria in both the db/db and the STZ-induced DN models with established disease, without modulating the HbA1c%. Albuminuria was strongly associated with loss of leukocytes, particularly B cells, but also of sub-populations of macrophages and CD4(+) T cells. The remaining kidney macrophages were polarized into a M2-like sub-population with reduced surface expression of the M1-like macrophage marker CD11c and enhanced expression of galectin-3. Enalapril treatment counteracted the reduction of leukocytes in the diabetic kidney towards levels noted in the non-diabetic kidney. Particularly, a subset of macrophages was increased and a clear expansion of CD4(+) and CD8(+) T cells was observed. However, enalapril failed to modulate the B cell compartment. Interestingly, enalapril treatment resulted in a re-polarization of the macrophages towards a M1-like phenotype characterized by elevated levels of CD11c with moderate down-regulation of the M2 marker galectin-3. The data demonstrate that ACE inhibition in pre-clinical models of DN shows a transient beneficial effect on albuminuria which is unexpectedly associated with restoration of T cells and M1-like macrophages in the kidney. PMID:25598292

Cucak, Helena; Nielsen Fink, Lisbeth; Højgaard Pedersen, Maiken; Rosendahl, Alexander



A Course-Based Research Experience: How Benefits Change with Increased Investment in Instructional Time  

PubMed Central

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit. PMID:24591510

Shaffer, Christopher D.; Alvarez, Consuelo J.; Bednarski, April E.; Dunbar, David; Goodman, Anya L.; Reinke, Catherine; Rosenwald, Anne G.; Wolyniak, Michael J.; Bailey, Cheryl; Barnard, Daron; Bazinet, Christopher; Beach, Dale L.; Bedard, James E. J.; Bhalla, Satish; Braverman, John; Burg, Martin; Chandrasekaran, Vidya; Chung, Hui-Min; Clase, Kari; DeJong, Randall J.; DiAngelo, Justin R.; Du, Chunguang; Eckdahl, Todd T.; Eisler, Heather; Emerson, Julia A.; Frary, Amy; Frohlich, Donald; Gosser, Yuying; Govind, Shubha; Haberman, Adam; Hark, Amy T.; Hauser, Charles; Hoogewerf, Arlene; Hoopes, Laura L. M.; Howell, Carina E.; Johnson, Diana; Jones, Christopher J.; Kadlec, Lisa; Kaehler, Marian; Silver Key, S. Catherine; Kleinschmit, Adam; Kokan, Nighat P.; Kopp, Olga; Kuleck, Gary; Leatherman, Judith; Lopilato, Jane; MacKinnon, Christy; Martinez-Cruzado, Juan Carlos; McNeil, Gerard; Mel, Stephanie; Mistry, Hemlata; Nagengast, Alexis; Overvoorde, Paul; Paetkau, Don W.; Parrish, Susan; Peterson, Celeste N.; Preuss, Mary; Reed, Laura K.; Revie, Dennis; Robic, Srebrenka; Roecklein-Canfield, Jennifer; Rubin, Michael R.; Saville, Kenneth; Schroeder, Stephanie; Sharif, Karim; Shaw, Mary; Skuse, Gary; Smith, Christopher D.; Smith, Mary A.; Smith, Sheryl T.; Spana, Eric; Spratt, Mary; Sreenivasan, Aparna; Stamm, Joyce; Szauter, Paul; Thompson, Jeffrey S.; Wawersik, Matthew; Youngblom, James; Zhou, Leming; Mardis, Elaine R.; Buhler, Jeremy; Leung, Wilson; Lopatto, David; Elgin, Sarah C. R.



Delay and déjà vu: timing and repetition increase the power of false evidence.  


False images and videos can induce people to believe in and remember events that never happened. Using a novel method, we examined whether the timing of false evidence would influence its effect (Experiment 1) and determined the relationship between timing and repetition (Experiment 2). Subjects completed a hazard perception driving test and were falsely accused of cheating. Some subjects were shown a fake video or photograph of the cheating either after a 9-min delay (Experiment 1) or more than once with or without a delay (Experiment 2). Subjects were more likely to falsely believe that they had cheated and to provide details about how the cheating happened when the false evidence was delayed or repeated-especially when repeated over time-relative to controls. The results show that even a strikingly short delay between an event and when false evidence is disclosed can distort people's beliefs and that repeating false evidence over a brief delay fosters false beliefs more so than without a delay. These findings have theoretical implications for metacognitive models of autobiographical memory and practical implications for police interrogations. PMID:23392652

Wright, Deborah S; Wade, Kimberley A; Watson, Derrick G



A course-based research experience: how benefits change with increased investment in instructional time.  


There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit. PMID:24591510

Shaffer, Christopher D; Alvarez, Consuelo J; Bednarski, April E; Dunbar, David; Goodman, Anya L; Reinke, Catherine; Rosenwald, Anne G; Wolyniak, Michael J; Bailey, Cheryl; Barnard, Daron; Bazinet, Christopher; Beach, Dale L; Bedard, James E J; Bhalla, Satish; Braverman, John; Burg, Martin; Chandrasekaran, Vidya; Chung, Hui-Min; Clase, Kari; Dejong, Randall J; Diangelo, Justin R; Du, Chunguang; Eckdahl, Todd T; Eisler, Heather; Emerson, Julia A; Frary, Amy; Frohlich, Donald; Gosser, Yuying; Govind, Shubha; Haberman, Adam; Hark, Amy T; Hauser, Charles; Hoogewerf, Arlene; Hoopes, Laura L M; Howell, Carina E; Johnson, Diana; Jones, Christopher J; Kadlec, Lisa; Kaehler, Marian; Silver Key, S Catherine; Kleinschmit, Adam; Kokan, Nighat P; Kopp, Olga; Kuleck, Gary; Leatherman, Judith; Lopilato, Jane; Mackinnon, Christy; Martinez-Cruzado, Juan Carlos; McNeil, Gerard; Mel, Stephanie; Mistry, Hemlata; Nagengast, Alexis; Overvoorde, Paul; Paetkau, Don W; Parrish, Susan; Peterson, Celeste N; Preuss, Mary; Reed, Laura K; Revie, Dennis; Robic, Srebrenka; Roecklein-Canfield, Jennifer; Rubin, Michael R; Saville, Kenneth; Schroeder, Stephanie; Sharif, Karim; Shaw, Mary; Skuse, Gary; Smith, Christopher D; Smith, Mary A; Smith, Sheryl T; Spana, Eric; Spratt, Mary; Sreenivasan, Aparna; Stamm, Joyce; Szauter, Paul; Thompson, Jeffrey S; Wawersik, Matthew; Youngblom, James; Zhou, Leming; Mardis, Elaine R; Buhler, Jeremy; Leung, Wilson; Lopatto, David; Elgin, Sarah C R



Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy  

SciTech Connect

Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 {+-} 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise [Departments of Radiation Physics and Radiation Oncology, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); The Proton Therapy Center Houston, Ltd., L.L.P., 1840 Old Spanish Trail, Houston, Texas 77054 (United States)



[Penetrating gunshot wounds of the chest: the surgical procedure and treatment times and outcomes].  


On the basis of data obtained during the war in Afghanistan the article analyses surgical management and the results of treatment in three groups of patients with chest wounds. The authors consider that the efficiency of treatment could be improved by gaining time during evacuation period and providing the earliest surgical care to the wounded. Indications and peculiarities for various surgical interventions were ascertained depending on the character of trauma and subsequent pathological disorders. The article proves the necessity of preventive sanitation of pleural cavity, gives the data concerning the period and outcome of treatment. PMID:1570690

Chepcheruk, G S; Shalaev, S A; Barinov, V S; Sorvari, Sh M



Time to discontinuation of antipsychotic drugs in a schizophrenia cohort: influence of current treatment strategies  

PubMed Central

Background Rates of discontinuation of antipsychotic treatment for patients with schizophrenia are high and evidence is limited by selective inclusion and high attrition in randomized controlled trials. Aims To study time to discontinuation of antipsychotic treatment for patients with schizophrenia. Method All patients with schizophrenia (n = 396) discharged between 2005 and 2011 were followed until discontinuation (clinician or patient decided) of antipsychotic treatment or other endpoints. Univariate and multivariate survival analyses (with time on antipsychotic treatment as the dependent variable) using time-dependent variables were performed. Results Clozapine displayed lower risk for all-cause (p < 0.001), clinician-decided (p = 0.012) and patient-decided (p = 0.039) discontinuation versus olanzapine oral treatment in the multivariate Cox regression. Second-generation long-acting injection antipsychotics (LAI) (p = 0.015) and first-generation long-acting injection antipsychotics (p = 0.013) showed significantly lower risks for patient-decided discontinuation than olanzapine oral. Conclusion Higher effectiveness of clozapine and LAI treatment versus oral olanzapine were identified in a clinical cohort of patients with schizophrenia. PMID:25489474

Kjelby, Eirik; Wentzel-Larsen, Tore; Mellesdal, Liv S.; Jørgensen, Hugo A.; Johnsen, Erik



Normalisation of real-time RT-PCR gene expression measurements in Arabidopsis thaliana exposed to increased metal concentrations  

Microsoft Academic Search

Accurate quantification by real-time RT-PCR relies on normalisation of the measured gene expression data. Normalisation with\\u000a multiple reference genes is becoming the standard, but the best reference genes for gene expression studies within one organism\\u000a may depend on the applied treatments or the organs and tissues studied. Ideally, reference genes should be evaluated in all\\u000a experimental systems. A number of

Tony Remans; Karen Smeets; Kelly Opdenakker; Dennis Mathijsen; Jaco Vangronsveld; Ann Cuypers



GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment.  


The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis. PMID:25491724

Wilson, Gabriel J; Lennox, Brittany A; She, Pengxiang; Mirek, Emily T; Al Baghdadi, Rana J T; Fusakio, Michael E; Dixon, Joseph L; Henderson, Gregory C; Wek, Ronald C; Anthony, Tracy G



Extension of Kaplan-Meier methods in observational studies with time-varying treatment  

PubMed Central

Objectives Inverse probability of treatment weighted (IPTW) Kaplan-Meier estimates have been developed to compare two treatments in the presence of confounders in observational studies. Recently, stabilized weights were developed to reduce the influence of extreme IPTW weights in estimating treatment effects. The objective of this paper was to use adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests to examine the effect of a treatment which varies over time in an observational study. Methods In this paper, we propose stabilized weight (SW) adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests when the treatment is time-varying over the follow-up period. We applied these new methods in examining the effect of an anti-platelet agent, clopidogrel, on subsequent events, including bleeding, myocardial infarction, and death after a Drug-Eluting Stent was implanted into a coronary artery. In this population, clopidogrel use may change over time based on patients' behavior (e.g., non-adherence) and physicians' recommendations (e.g., end of duration of therapy). Consequently, clopidogrel use was treated as a time-varying variable. Results We demonstrate that 1) the sample sizes at three chosen time points are almost identical in the original and weighted datasets, and 2) the covariates between patients on and off clopidogrel were well balanced after SWs were applied to the original samples. Conclusions The SW-adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests are useful in presenting and comparing survival functions for time-varying treatments in observational studies while adjusting for known confounders. PMID:22264985

Xu, Stanley; Shetterly, Susan; Powers, David; Raebel, Marsha A.; Thomas Tsai, MD; Ho, P. Michael; Magid, David



Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.  


Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500?cells/?L, while the threshold for the UK and South Africa remains at 350?cells/?L. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500?cells/?L or higher versus deferring treatment until the CD4 cell count decreases to 350?cells/?L or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people. PMID:25711318

Geffen, N; Aagaard, P; Corbelli, Gm; Meulbroek, M; Peavy, D; Rappoport, C; Schwarze, S; Collins, S



Searching for scalable processes: addressing the challenges in times of increasing complexity.  


The position of the pharmaceutical industry at the beginning of the 21st Century and its role in process research and development are important considerations. Based on recent figures and statistics, it is evident that new and maybe unorthodox ways of operating need to be envisaged to counteract the explosive rise in research and development costs (> US $800 million per successful launch in 2002) and the worryingly high level of attrition (approximately 90%), which, in addition to long handling times for authority approval, lead to a continued decline in the number of drugs entering the market. In addition to pointing out these harsh realities, it is essential to remember that the time taken to bring a new product forward is crucial. In this context, a front-loading model has been developed and applied in AstraZeneca's process research and development. The enormous implications of chirality in the pharmacological arena have been fully acknowledged for many years, and sales figures of chiral molecules corroborate the importance of this feature. The methodologies that are available to address the design and scale-up of production methods are also reviewed against a backdrop of recent in-house cases. PMID:14758755

Federsel, Hans-Jürgen



Diastolic Timed Vibrator: Noninvasive Pre-Hospitalization Treatment of Acute Coronary Ischemia.  


The speed of intervention is one of the major factors in increasing the survival rate of patients suffering from acute coronary ischemia. The two principal techniques currently in use: pharmacological and interventional, can be employed to re-canalize coronary arteries, but the former is slow acting and often leads to incomplete reperfusion, while the latter requires specialized personnel in a hospital with a cardiac catheterization laboratory. In this paper, we introduce a novel method intended for pre-hospitalization treatment of patients with acute coronary ischemia that can be safely applied by a minimally trained individual prior to or during patient transportation to hospital. It consists in applying low frequency mechanical vibrations to the left intercostal space of patient's chest during diastole of the heart cycle, to induce vibrations of the heart and thus of the coronary arteries. Mechanical vibrations stimulate mixing of blood which improves drug delivery to the occlusion site, applies mechanical force on the clot leading to its faster dissolution and finally acts as a strong vasodilator in case of spasms. We introduce the principle of operation and the architecture of the Diastolic Timed Vibrator (DTV), including a custom ECG processing algorithm, vibration pattern generator and active braking methods. Experimental results demonstrate the functionality of the DTV device and pave way for in-vivo tests necessary for clinical confirmation of the proposed method. PMID:23934670

Marzencki, Marcin; Kajbafzadeh, Behrad; Khosrow-Khavar, Farzad; Tavakolian, Kouhyar; Kaminska, Bozena; Menon, Carlo



Environmental Enrichment Preceding Early Adulthood Methylphenidate Treatment Leads to Long Term Increase of Corticosterone and Testosterone in the Rat  

PubMed Central

Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30–60] rats were reared in EE and were treated with MPH during early adulthood (PND 60–90). Adult (PND 90–92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences. PMID:21789212

Avital, Avi; Dolev, Talya; Aga-Mizrachi, Shlomit; Zubedat, Salman



Systems Biology Investigation of cAMP Modulation to Increase SMN Levels for the Treatment of Spinal Muscular Atrophy  

PubMed Central

Spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an autosomal recessive disorder caused by the loss of SMN1 (survival motor neuron 1), which encodes the protein SMN. The loss of SMN1 causes a deficiency in SMN protein levels leading to motor neuron cell death in the anterior horn of the spinal cord. SMN2, however, can also produce some functional SMN to partially compensate for loss of SMN1 in SMA suggesting increasing transcription of SMN2 as a potential therapy to treat patients with SMA. A cAMP response element was identified on the SMN2 promoter, implicating cAMP activation as a step in the transcription of SMN2. Therefore, we investigated the effects of modulating the cAMP signaling cascade on SMN production in vitro and in silico. SMA patient fibroblasts were treated with the cAMP signaling modulators rolipram, salbutamol, dbcAMP, epinephrine and forskolin. All of the modulators tested were able to increase gem formation, a marker for SMN protein in the nucleus, in a dose-dependent manner. We then derived two possible mathematical models simulating the regulation of SMN2 expression by cAMP signaling. Both models fit well with our experimental data. In silico treatment of SMA fibroblasts simultaneously with two different cAMP modulators resulted in an additive increase in gem formation. This study shows how a systems biology approach can be used to develop potential therapeutic targets for treating SMA. PMID:25514431

Mack, Sean G.; Cook, Daniel J.; Dhurjati, Prasad; Butchbach, Matthew E. R.



Sub-volume Heating Strategy To Shorten Treatment Time In Ultrasound Surgery  

NASA Astrophysics Data System (ADS)

Treating tumors or other potentially large targets for thermal ablation can be a very time-consuming task in ultrasound surgery. Tumors are conventionally treated by pointwise scanning over the tumor region using predetermined focal points. During scanning, cooling times are needed between two consecutive focal points to diffuse thermal buildup in the near field, which can prevent undesired temperature rises in healthy tissue. It is possible to accelerate the treatment while ensuring the safety of healthy tissue by reallocation of the heating and cooling times for individual focus points. In this study, we proposed a sub-volume heating strategy by reducing the number of cooling periods, to shorten the treatment time. The target volume is divided into several equally sized sub-volumes, each of which is covered by the same number of focal points. The sub-volume is sonicated, followed by a constant cooling period (the number of cooling periods = the number of sub-volumes). The proposed strategy was evaluated with numerical simulations in 3D and ex vivo experiments using three different: (1) a `conservative' approach, wherein each focal point is a sub-volume; (2) an `aggressive' approach, wherein all focal points make up a sub-volume; and (3) an `intermediate' approach, wherein several focus points make up a sub-volume. The results demonstrate the efficacy of this strategy; it was able to effectively reduce the treatment times by decreasing total cooling times. This study indicated that by appropriate selection of the sub-volume size and heating sequence, it may be useful to overcome the current obstacle of treatment time during large tumor treatments.

Xiang, Ji; Guofeng, Shen; Jingfeng, Bai; Yazhu, Chen



Time and motion study for alternative mixed low-level waste treatment systems  

SciTech Connect

The time and motion study was developed to look at time-related aspects of the technologies and systems studied in the Integrated Thermal Treatment Systems (ITTS) and Integrated Nonthermal Treatment Systems (INTS) studies. The INTS and ITTS studies combined technologies into systems and subsystems for evaluation. The system approach provides DOE a method of measuring advantages and disadvantages of the many technologies currently being researched. For example, technologies which are more likely to create secondary waste or require extensive pretreatment handling may be less desirable than technologies which require less support from other processes. The time and motion study was designed to address the time element in the INTS and ITTS systems studies. Previous studies have focused on material balance, cost, technical effectiveness, regulatory issues, community acceptance, and operability. This study looks at system dynamics by estimating the treatment time required for a unit of waste, from receipt to certification for shipping. Labor estimates are also developed, based on the time required to do each task for each process. This focus on time highlights critical path processes and potential bottlenecks in the INTS and ITTS systems.

Biagi, C.; Vetromile, J.; Teheranian, B.



Increasing the time resolution of a pulse width modulator in a class D power amplifier by using delay lines  

NASA Astrophysics Data System (ADS)

In this paper, we present a method to increase the time resolution of a pulse width modulator by using delay lines. The modulator is part of an open loop class D power amplifier, which uses the ZePoC algorithm to code the audio signal which is amplified in the class D power stage. If the time resolution of the pulse width modulator is high enough, ZePoC could also be used to build an high accuracy AC power standard, because of its open loop property. With the presented method the time resolution theoretically could be increased by a factor of 16, which means here the time resolution will be enhanced from 5 ns to 312.5 ps.

Weber, M.; Vennemann, T.; Mathis, W.



Time at Treatment of Severe Retinopathy of Prematurity in China: Recommendations for Guidelines in More Mature Infants  

PubMed Central

Purpose To investigate the postmenstrual (PMA) age at treatment of severe retinopathy of prematurity (i.e. Type 1 prethreshold or threshold) in infants in a tertiary referral center in China. Principal Findings 76.6% (359/469) of infants were treated for threshold disease. 67.5% (317/469) of infants had a birth weight (BW) of 1250g or above and almost 30% (126) had a gestational age (GA) of 32 weeks or above. There was little difference in the characteristics of infants treated for Type 1 prethreshold or threshold ROP. After controlling for GA, PMA age at treatment was highest in infants with BW ?2000g (mean PMA 40.3±4.4 weeks, p<0.001); after controlling for BW, higher GA was associated with higher PMA at treatment (mean PMA 41.5 weeks for gestational age >34 weeks, p<0.001). For every three weeks increase in GA there was a two-week increase in PMA at treatment (R2 = 0.20, p<0.001). The time at treatment of Type 1 prethreshold disease was similar to that for threshold disease i.e. chronological age 5.6?7.4 weeks, or PMA 34.1?40.2 weeks but the lower end of the 95% confidence interval for chronological age for Type 1 prethreshold disease among infants with BW ?2000g was 3.7 weeks (i.e. before the recommended interval of 4?6 weeks after birth). Significance The Chinese guidelines regarding timing of the first examination are appropriate for infants with BW <2000g, but more mature infants should be examined a little earlier, at 3 weeks after birth, in order to detect Type 1 prethreshold disease which has a better prognosis than threshold. PMID:25664992

Chen, Yi; Feng, Jing; Gilbert, Clare; Yin, Hong; Liang, Jianhong; Li, Xiaoxin



Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment.  


The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000-2011. In 2003, the year before ART became available in the public-sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years--an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for the investment decisions of individuals, governments, and donors. PMID:23430655

Bor, Jacob; Herbst, Abraham J; Newell, Marie-Louise; Bärnighausen, Till



Topotecan Can Compensate for Protracted Radiation Treatment Time Effects in High Grade Glioma Xenografts  

Microsoft Academic Search

Summary  Purpose:\\u000a Several studies reported that prolongation of overall treatment time of fractionated radiotherapy reduces the chance of tumor\\u000a control. In the present study, we hypothesize that combining topotecan with irradiation could compensate for this detrimental\\u000a time effect on the radioresponse. Therefore, we investigated the efficiency of different schedules of topotecan (TPT), radiotherapy\\u000a (RT) or concomitant combination TPT + RT.\\u000a \\u000a Methods

Sophie Pinel; Pascal Chastagner; Jean-Louis Merlin; Christian Marchal; Alphonse Taghian; Muriel Barberi-Heyob



Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function  

PubMed Central

BACKGROUND AND PURPOSE PPAR? agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. EXPERIMENTAL APPROACH Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg?1·day?1, 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. KEY RESULTS In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI2) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. CONCLUSIONS AND IMPLICATIONS Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. PMID:22220498

Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J



Increased efficacy for in-house validation of real-time PCR GMO detection methods.  


To improve the efficacy of the in-house validation of GMO detection methods (DNA isolation and real-time PCR, polymerase chain reaction), a study was performed to gain insight in the contribution of the different steps of the GMO detection method to the repeatability and in-house reproducibility. In the present study, 19 methods for (GM) soy, maize canola and potato were validated in-house of which 14 on the basis of an 8-day validation scheme using eight different samples and five on the basis of a more concise validation protocol. In this way, data was obtained with respect to the detection limit, accuracy and precision. Also, decision limits were calculated for declaring non-conformance (>0.9%) with 95% reliability. In order to estimate the contribution of the different steps in the GMO analysis to the total variation variance components were estimated using REML (residual maximum likelihood method). From these components, relative standard deviations for repeatability and reproducibility (RSD(r) and RSD(R)) were calculated. The results showed that not only the PCR reaction but also the factors 'DNA isolation' and 'PCR day' are important factors for the total variance and should therefore be included in the in-house validation. It is proposed to use a statistical model to estimate these factors from a large dataset of initial validations so that for similar GMO methods in the future, only the PCR step needs to be validated. The resulting data are discussed in the light of agreed European criteria for qualified GMO detection methods. PMID:20012027

Scholtens, I M J; Kok, E J; Hougs, L; Molenaar, B; Thissen, J T N M; van der Voet, H




PubMed Central

Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years) participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg-1 body weight) or placebo was given to the subjects after 12 hours fasting (during the night) for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg-1 · min-1, placebo 52.07±5.21 mL · kg-1 · min-1) or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm) between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s) compared to placebo (1313±90.8 s) (p < 0.05). These results suggest that L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects. PMID:25177096

Turnagol, H.; Demirel, A.H.



Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.  


Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-?, adiponectin, LPL and C/EBP-? from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia. PMID:25807446

Beluzi, Mércia; Peres, Sidney B; Henriques, Felipe S; Sertié, Rogério A L; Franco, Felipe O; Santos, Kaltinaitis B; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S; Neves, Rodrigo X; Farmer, Stephen R; Seelaender, Marília; Lima, Fábio B; Batista, Miguel L



Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: A new potential therapy for the treatment of melanoma  

SciTech Connect

Resistance of cancer cells to apoptosis is dependent on a balance of multiple genetic and epigenetic mechanisms, which up-regulate efficacy of the surviving growth factor-receptor signaling pathways and suppress death-receptor signaling pathways. The Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling pathway is highly active in metastatic melanoma cells by mediating downstream activation of PI3K-AKT and MAPK pathways and controlling general cell survival and proliferation. In the present study, we used human melanoma lines with established genotypes that represented different phases of cancer development: radial-growth-phase WM35, vertical-growth-phase WM793, metastatic LU1205 and WM9 [1]. All these lines have normal NRAS. WM35, WM793, LU1205 and WM9 cells have mutated BRAF (V600E). WM35 and WM9 cells express normal PTEN, while in WM793 cells PTEN expression is down-regulated; finally, in LU1205 cells PTEN is inactivated by mutation. Cyclolignan picropodophyllin (PPP), a specific inhibitor of IGF-1R kinase activity, strongly down-regulated the basal levels of AKT activity in WM9 and in WM793 cells, modestly does so in LU1205, but has no effect on AKT activity in the early stage WM35 cells that are deficient in IGF-1R. In addition, PPP partially down-regulated the basal levels of active ERK1/2 in all lines used, highlighting the role of an alternative, non-BRAF pathway in MAPK activation. The final result of PPP treatment was an induction of apoptosis in WM793, WM9 and LU1205 melanoma cells. On the other hand, dose-dependent inhibition of IGF-1R kinase activity by PPP at a relatively narrow dose range (near 500 nM) has different effects on melanoma cells versus normal cells, inducing apoptosis in cancer cells and G2/M arrest of fibroblasts. To further enhance the pro-apoptotic effects of PPP on melanoma cells, we used a combined treatment of TNF-Related Apoptosis-Inducing Ligand (TRAIL) and PPP. This combination substantially increased death by apoptosis for WM793 and WM9 cells, but did so only modestly for LU1205 cells with very high basal activity of AKT. The ultimate goal of this direction of research is the discovery of a new treatment method for highly resistant human metastatic melanomas. Our findings provide the rationale for further preclinical evaluation of this novel treatment.

Karasic, Thomas B.; Hei, Tom K. [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)] [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Ivanov, Vladimir N., E-mail: [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)



Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor–Bearing Animals: Possible Anti-Cachectic Effect  

PubMed Central

Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-?, adiponectin, LPL and C/EBP-? from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia. PMID:25807446

Beluzi, Mércia; Peres, Sidney B.; Henriques, Felipe S.; Sertié, Rogério A. L.; Franco, Felipe O.; Santos, Kaltinaitis B.; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S.; Neves, Rodrigo X.; Farmer, Stephen R.; Seelaender, Marília; Lima, Fábio B.; Batista Jr., Miguel L.



Biochemical and histopathological changes induced by different time intervals of methomyl treatment in mice liver  

Microsoft Academic Search

The present study was designed to evaluate the toxic effects induced by different time intervals of methomyl exposure on liver antioxidant defense system, oxidative stress, liver function biomarkers and histopathology in CD-1 mice. Ten male mice per group were assigned to one of four treatment groups. Group one served as control while group 2, 3 and 4 were orally treated

Fatma El-Demerdash; Azza A. Attia; Reda H. Elmazoudy



Fixed-time schedules attenuate extinction-induced phenomena in the treatment of severe aberrant behavior  

Microsoft Academic Search

We compared the effects of extinction (EXT) and fixed-time (FT) schedules as treatment for severe problem behavior displayed by 3 individuals with developmental disabilities. First, functional analyses identified the reinforcers maintaining aberrant behavior for all 3 individuals. Next, EXT and FT schedules were compared using a multielement design. During EXT, the reinforcer maintaining problem behavior was withheld. During FT, the

TIMOTHY R. VOLLMER; P ATRICK R. PROGAR; J OSEPH S. LALLI; C M Van Camp; B J Sierp; C S Wright; J Nastasi; K J Eisenschink



Acute Time to Response in the Treatment for Adolescents with Depression Study (TADS)  

ERIC Educational Resources Information Center

Objective: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). Method: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo…

Kratochvil, Christopher; Emslie, Graham; Silva, Susan; McNulty, Steve; Walkup, John; Curry, John; Reinecke, Mark; Vitiello, Benedetto; Rohde, Paul; Feeny, Nora; Casat, Charles; Pathak, Sanjeev; Weller, Elizabeth; May, Diane; Mayes, Taryn; Robins, Michele; March, John



What Can We Learn about Inflation Targeting? Evidence from Time-Varying Treatment Effects  

E-print Network

What Can We Learn about Inflation Targeting? Evidence from Time-Varying Treatment Effects Wen of Economics Feng Chia University Abstract Recent studies that evaluate inflation targeting through average, developed countries lower inflation and reach their targets rapidly in two years and developing countries

Ahmad, Sajjad


Time Course of Treatment Effect of OROS[R] Methylphenidate in Children with ADHD  

ERIC Educational Resources Information Center

Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS[R] MPH) HCl (Concerta[R], Raritan, NJ) CII in children with ADHD. Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD.…

Armstrong, Robert B.; Damaraju, C. V.; Ascher, Steve; Schwarzman, Lesley; O'Neill, James; Starr, H. Lynn



Multivariate time series analysis for design and operation of a biological wastewater treatment plant  

Microsoft Academic Search

In the area of biological wastewater treatment, the more common approach to dynamical modeling has been the use of mechanistic models with differential equations. This study illustrates that multivariate time series analysis can be a valid alternative. A lab-scale activated sludge unit, treating brewery wastewater, was operated with a highly variable COD-load. For design and operation purposes, we wanted to

G. Van Dongen; L. Geuens



Trends in time to invasive examination and treatment from 2001 to 2009 in patients admitted first time with non-ST elevation myocardial infarction or unstable angina in Denmark  

PubMed Central

Objective To investigate trends in time to invasive examination and treatment for patient with first time diagnosis of non-ST elevation myocardial infarction (NSTEMI) and unstable angina during the period from 2001 to 2009 in Denmark. Design From 1 January 2001 to 31 December 2009 all first time hospitalisations with NSTEMI and unstable angina were identified in the National Patient Registry (n=65?909). Time from admission to initiation of coronary angiography (CAG), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was calculated. We described the development in invasive examination and treatment probability (CAG, PCI and CABG at 3, 7, 10, 30 and 60?days) for the years 2001–2009, taking the competing risk of death into account using Aalen–Johansen estimators and a Fine-Gray model. Setting Nationwide Danish cohort. Results The proportion of patients receiving a CAG and PCI increased substantially over time while the proportion receiving a CABG decreased for both NSTEMI and unstable angina. For both NSTEMI and unstable angina, a significant increase in invasive examination and treatment probability at 3?days for CAG and PCI were seen especially from 2007 through to 2009. For NSTEMI, the CAG examination probability at 3?days leaped from 20% in 2007 to 32% in 2008 and 39% in 2009, and for PCI the same was true with a leap in treatment probability from 19% to 28% from 2008 to 2009. Conclusions In Denmark the use of CAG and PCI in treatment of NSTEMI and unstable angina has increased from 2001 to 2009, while the use of CABG has decreased. During the same period, there was a marked increase in invasive examination and treatment probability at 3?days, that is, more patients were treated faster which is in line with the political aim of reducing time to treatment. PMID:24413349

Mårtensson, Solvej; Gyrd-Hansen, Dorte; Prescott, Eva; Andersen, Per Kragh; Zwisler, Ann-Dorthe Olsen; Osler, Merete



'Mind the Gap'-The Impact of Variations in the Duration of the Treatment Gap and Overall Treatment Time in the First UK Anal Cancer Trial (ACT I)  

SciTech Connect

Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

Glynne-Jones, Rob, E-mail: [Mount Vernon Centre for Cancer Treatment, Northwood (United Kingdom); Sebag-Montefiore, David [St James's Institute of Oncology, St James's University Hospital, Leeds (United Kingdom); Adams, Richard [Cardiff University and Velindre Cancer Centre, Cardiff (United Kingdom); McDonald, Alec [Beatson West of Scotland Cancer Centre, Glasgow (United Kingdom); Gollins, Simon [North Wales Cancer Treatment Centre, Rhyl (United Kingdom); James, Roger [Kent Oncology Centre, Maidstone General Hospital, Maidstone (United Kingdom); Northover, John M.A. [Imperial Cancer Research Fund Colorectal Cancer Unit, St Mark's Hospital, Harrow (United Kingdom); Meadows, Helen M.; Jitlal, Mark [Cancer Research UK and University College London Cancer Trials Centre, London (United Kingdom)



A Randomized Controlled Trial of Increased Dose and Frequency of Albendazole with Standard Dose DEC for Treatment of Wuchereria bancrofti Microfilaremics in Odisha, India  

PubMed Central

Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P



Protein denaturation and water-protein interactions as affected by low temperature long time treatment of porcine longissimus dorsi.  


The relationship between water-protein interactions and heat-induced protein denaturation in low temperature long time (LTLT) treated pork Longissimus dorsi was investigated by combining low-field NMR T? relaxometry with DSC measurements and measures of shrinkage of porcine Longissimus dorsi heated to 53 °C, 55 °C, 57 °C and 59 °C for either 3 or 20 h. Water within the myofibrils, measured by NMR T?? relaxation times, was affected by both temperature and holding time during LTLT treatment between 53 °C and 59 °C. The changes in NMR T?? relaxation times were associated with decreased fiber diameter and increased cooking loss, revealing a relationship between transverse shrinkage, water-protein interactions and cooking loss. DSC measurements revealed a concomitant decrease in ?H(68 °C), which suggests impact of collagen denaturation on the retention of water within the meat during LTLT treatment. Furthermore, a decrease in ?H(75 °C) suggested that prolonged cooking (20 h) resulted in actin denaturation leading to decreased T?? relaxation times and higher cooking loss. PMID:21450413

Christensen, Line; Bertram, Hanne C; Aaslyng, Margit D; Christensen, Mette



Accelerated increase in mercury contamination in north Atlantic mesopelagic food chains as indicated by time series of seabird feathers  

Microsoft Academic Search

Concentrations of mercury in the environment have increased manyfold since preindustrial times as a result of anthropogenic emissions of gaseous mercury to the atmosphere. However, most records of historical change are affected by regional inputs and evidence of global impact of human activities at pristine oceanic sites is scanty. Seabird feathers contain a valuable record showing historical trends in methylmercury

Luís R. Monteiro; Robert W. Furness



Abstract --Real time traffic incident detection is critical for increasing safety and mobility on freeways. There have been  

E-print Network

in varies of speed with large amount, quick and reliable automatic detection of traffic incidents becomes. An incrementally learning method is proposed as well to keep the historical traffic model up-to-date. ProposedAbstract -- Real time traffic incident detection is critical for increasing safety and mobility

Bailey-Kellogg, Chris


Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells  

PubMed Central

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and ?-tubulin were detected after neurogenesis as neural markers. Ten ?M of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology. PMID:24024202

Rahmani, Anahita; Kheradmand, Danial; Keyhanvar, Peyman; Darbandi-Azar, Amir



Social crowding in the night-time reduces an anxiety-like behavior and increases social interaction in adolescent mice.  


Rearing in crowded conditions is a psychosocial stressor that affects biological functions. The effects of continuous crowding for many days have been studied, but those of crowding over a limited time have not. In this study, we examined the effects of night-time or daytime crowding over 2 weeks on behavior in adolescent and adult mice. Crowding (20 mice/cage) in either the night-time or daytime did not affect locomotor activity in the open field test or cognitive function in the fear conditioning test. In contrast, night-time crowding, but not daytime crowding, had an anxiolytic effect in the elevated plus-maze test and increased social interaction in adolescent mice, but not in adult mice. The first night-time, but not daytime, crowding increased plasma corticosterone levels in adolescent mice, although night-time crowding over 2 weeks did not affect the corticosterone levels. Furthermore, no significant effects of the first crowding were observed in adult mice. In a second crowding condition (six mice/small cage), the anxiolytic-like effects of night-time crowding and the change in plasma corticosterone levels were not observed, suggesting that the density of mice is not important for the behavioral consequences of crowding. Night-time crowding did not affect neurotrophic/growth factor levels and hippocampal neurogenesis in adolescent mice. These findings suggest that night-time crowding leads to anxiolytic-like behaviors in adolescent mice, and imply that night-time crowding stress in adolescence may be beneficial to brain functions. PMID:24803212

Ago, Yukio; Tanaka, Tatsunori; Ota, Yuki; Kitamoto, Mari; Imoto, Emina; Takuma, Kazuhiro; Matsuda, Toshio



Predictors of time to requiring dopaminergic treatment in 2 Parkinson's disease cohorts.  


The rate of progression of Parkinson's disease (PD) is highly variable. Knowledge of factors associated with disease milestones and commonly used research outcome measures helps with patient counseling and guides the design and interpretation of clinical studies. The objective of the study was to identify prognostic factors for time to acquiring disability requiring dopaminergic therapy that are reproducible within 2 large prospectively followed cohorts. Potential prognostic factors were identified using data from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial, and their reproducibility was examined using data from the Parkinson Research Examination of CEP-1347 trial (PRECEPT). In multivariable analyses of the DATATOP cohort, higher baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores, full-time employment, a lesser smoking history, and onset on the left side were associated with a shorter time to disability requiring dopaminergic therapy. PRECEPT data confirmed the associations of higher baseline UPDRS scores and full-time employment with shorter time to requiring treatment. Any clinical trial using the end point of time to disability requiring dopaminergic therapy should ensure that groups are well balanced with respect to baseline UPDRS scores and the proportion of subjects employed full time and should consider including these variables as covariates in the statistical model for primary analysis of treatment effects. We suspect that individuals employed full time may have a lower threshold for requiring dopaminergic therapy because of occupational demands. PMID:21287602

Marras, Connie; McDermott, Michael P; Marek, Ken; Rochon, Paula; Naglie, Gary; Tanner, Caroline M; Rudolph, Alice; Shoulson, Ira; Lang, Anthony E



Prion (PrPC) expression in ovine uteroplacental tissues increases after estrogen treatment of ovariectomized ewes and during early pregnancy.  


Scrapie in sheep is spread laterally by placental transmission of an infectious misfolded form (PrPSc) of a normal prion protein (PrPC) used as a template in PrPSc formation. We hypothesized that PrPC would be expressed in uterine and placental tissues and estradiol-17? (E2) would affect uterine PrPC expression. PrPC expression was evaluated in the uterus of long-term ovariectomized (OVX) ewes treated with an E2 implant for 2-24?h and in uteroplacental tissues from day 20 to day 30 of pregnancy. Expression of PrPC mRNA and PrPC protein increased in the uterus after E2 treatment of OVX ewes. In the maternal placenta, expression of PrPC mRNA and PrPC protein were unchanged, but in the fetal membranes (FM) PrPC mRNA and PrPC protein expression increased from day 20 to day 28. In the nonpregnant uterus, PrPC protein was immunolocalized at apical borders of the surface epithelium, in outer smooth muscle layers of large blood vessels, and in scattered stromal cells of the deep intercaruncular areas of the uterus. In the maternal placenta, PrPC protein was immunolocalized in the cytoplasm of flattened luminal epithelial cells apposed to the FM, whereas in the FM PrPC protein was in trophoblast cells and was also in several tissues of the developing embryo during early pregnancy. These data linking estrogen stimulation to increases in PrPC expression in uteroplacental tissues suggest that PrPC has a specific function during the estrous cycle and early pregnancy. Future studies should determine whether or not estrogen influences PrPC expression in other tissues, such as the nervous system and brain. PMID:24664411

Johnson, Mary Lynn; Grazul-Bilska, Anna T; Reynolds, Lawrence P; Redmer, Dale A



Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue  

PubMed Central

The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucleotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury. PMID:25657738

Rosas, Odrick R.; Torrado, Aranza I.; Santiago, Jose M.; Rodriguez, Ana E.; Salgado, Iris K.; Miranda, Jorge D.



Alzheimer's Disease: Differences of Transdermal versus Oral Treatment on Caregiving Time  

PubMed Central

Background Data on indirect effects of dementia treatment on caregiver burden obtained from naturalistic studies are still lacking. We explored differences between patients with oral and transdermal application of acetylcholine esterase inhibitors regarding caregiver's time burden and psychopathology. Methods A cross-sectional naturalistic cohort study of 403 patients in outpatient care with three treatment groups (none, oral, and transdermal) was conducted. Assessments included a standardized clinical burden questionnaire and a standardized caregiver interview. Results Any treatment was associated with lower burden in most measures. Transdermal treatment was superior regarding (1) administration time (p < 0.001); (2) rates of administration problems (p = 0.031); (3) burden in activities of daily living (p = 0.008), and (4) caregiver anxiety (OR 0.25; 95% CI 0.05–0.99). Caregivers did not report better quality of life regarding mental/physical health. Physicians’ and caregivers’ ratings of patients’ improvements were not associated (? = 0.01–0.06). Conclusions Benefits associated with transdermal treatment do not translate into a better ‘generic quality of life’ of the caregiver. The substantially different perceptions of patients’ improvements need to be considered in future studies. PMID:23277781

Riedel, O.; Emmrich, A.; Klotsche, J.; Dodel, R.; Förstl, H.; Maier, W.; Reichmann, H.; Wittchen, H.-U.



Effects of Prolongation of Overall Treatment Time Due To Unplanned Interruptions During Radiotherapy of Different Tumor Sites and Practical Methods for Compensation  

SciTech Connect

The prescribed total radiation dose should be administered within a specific time. In daily clinical practice, however, unplanned treatment interruptions resulting in prolongation of the overall treatment time are predictable. The present review evaluated the existing published data regarding the affect of the prolongation of the overall treatment time on the tumor control rate and outcome of patients with head-and-neck, lung, and uterine cervical cancer and other treatment sites. In most studies, including the planned interruption (split-course) schedules, as well as the retrospective studies analyzing the role of overall treatment time, a detrimental effect from the treatment break on the outcome was evident. This is suggestive of the deleterious effect of accelerated repopulation of tumor clonogens. In particular for the cancers of the head and neck for which the evidence is the strongest for such a consequence, even a 1-day interruption resulted in a decrease in the local control rate by 1.4%. Although the increased number of gaps was associated with a negative outcome, the data are contradictory concerning the effect of the number of gaps. The main recommendation is to exert all efforts to retain the planned irradiation schedule; however, existing data have shown that interruptions that effect the programmed time-course for irradiation need to be compensated for. This is to ensure biologic equivalence in treatment efficacy compared with uninterrupted regimens with respect to cancer site and stage. Practical methods for compensation using radiobiologic modeling and their limitations are also discussed.

Bese, Nuran Senel [Department of Radiation Oncology, Istanbul University Cerrahpasa Medical School, Cerrahpasa, Istanbul (Turkey)]. E-mail:; Hendry, Jolyon [International Atomic Energy Agency, Vienna (Austria); Jeremic, Branislav [International Atomic Energy Agency, Vienna (Austria)



Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?  


Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces "detrimental" effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a "substitute" mother. The maternal care of biological and "substitute" mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the "substitute" mother did not exhibit overt maltreatment. A mixture of "detrimental" and "beneficial" effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may "buffer" the effects of ELS in a context-dependent manner. PMID:24616673

Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser



Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?  

PubMed Central

Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “detrimental” effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “substitute” mother. The maternal care of biological and “substitute” mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behavior by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the “substitute” mother did not exhibit overt maltreatment. A mixture of “detrimental” and “beneficial” effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behavior. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may “buffer” the effects of ELS in a context-dependent manner. PMID:24616673

Fuentes, Sílvia; Daviu, Núria; Gagliano, Humberto; Garrido, Pedro; Zelena, Dóra; Monasterio, Nela; Armario, Antonio; Nadal, Roser



Tiam1 Transgenic Mice Display Increased Tumor Invasive and Metastatic Potential of Colorectal Cancer after 1,2-Dimethylhydrazine Treatment  

PubMed Central

Background T lymphoma invasion and metastasis 1 (Tiam1) is a potential modifier of tumor development and progression. Our previous study in vitro and in nude mice suggested a promotion role of Tiam1 on invasion and metastasis of colorectal cancer (CRC). In the present study, we generated Tiam1/C1199-CopGFP transgenic mice to investigate the tumorigenetic, invasive and metastatic alterations in the colon and rectum of wild-type and Tiam1 transgenic mice under 1,2-dimethylhydrazine (DMH) treatment. Methods Transgenic mice were produced by the method of pronuclear microinlectlon. Whole-body fluorescence imaging (Lighttools, Edmonton, Alberta, Canada), PCR, and immunohistochemical techniques (IHC) were applied sequentially to identify the transgenic mice. The carcinogen DMH (20 mg/kg) was used to induce colorectal tumors though intraperitoneal (i.p.) injections once a week for 24 weeks from the age of 4 weeks on Tiam1 transgenic or non-transgenic mice. Results We successfully generated Tiam1/C1199-CopGFP transgenic mice and induced primary tumors in the intestine of both wild type and Tiam1 transgenic mice by DMH treatment. In addition, Tiam1 transgenic mice developed larger and more aggressive neoplasm than wild-type mice. Moreover, immunohistochemical staining revealed that upregulation of Tiam1 was correlated with increased expression of ?-Catenin and Vimentin, and downregulation of E-Cadherin in these mice. Conclusions Our study has provided in vivo evidence supporting that Tiam1 promotes invasion and metastasis of CRC, most probably through activation of Wnt/?-catenin signaling pathway, in a Tiam1 transgenic mouse model. PMID:24069171

Yu, Li-Na; Zhang, Qing-Ling; Li, Xin; Hua, Xing; Cui, Yan-Mei; Zhang, Nian-Jie; Liao, Wen-Ting; Ding, Yan-Qing



A simple method of independent treatment time verification in gamma knife radiosurgery using integral dose  

SciTech Connect

The purpose of this study is to develop a simple independent dose calculation method to verify treatment plans for Leksell Gamma Knife radiosurgery. Our approach uses the total integral dose within the skull as an end point for comparison. The total integral dose is computed using a spreadsheet and is compared to that obtained from Leksell GammaPlan registered . It is calculated as the sum of the integral doses of 201 beams, each passing through a cylindrical volume. The average length of the cylinders is estimated from the Skull-Scaler measurement data taken before treatment. Correction factors are applied to the length of the cylinder depending on the location of a shot in the skull. The radius of the cylinder corresponds to the collimator aperture of the helmet, with a correction factor for the beam penumbra and scattering. We have tested our simple spreadsheet program using treatment plans of 40 patients treated with Gamma Knife registered in our center. These patients differ in geometry, size, lesion locations, collimator helmet, and treatment complexities. Results show that differences between our calculations and treatment planning results are typically within {+-}3%, with a maximum difference of {+-}3.8%. We demonstrate that our spreadsheet program is a convenient and effective independent method to verify treatment planning irradiation times prior to implementation of Gamma Knife radiosurgery.

Jin Jianyue; Drzymala, Robert; Li Zuofeng [Department of Radiation Oncology, Siteman Cancer Center, Washington University Medical Center, St. Louis, Missouri 63110 (United States)



Increased levels of multiresistant bacteria and resistance genes after wastewater treatment and their dissemination into lake geneva, Switzerland.  


At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne's wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed. PMID:22461783

Czekalski, Nadine; Berthold, Tom; Caucci, Serena; Egli, Andrea; Bürgmann, Helmut



Increased Levels of Multiresistant Bacteria and Resistance Genes after Wastewater Treatment and Their Dissemination into Lake Geneva, Switzerland  

PubMed Central

At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne’s wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed. PMID:22461783

Czekalski, Nadine; Berthold, Tom; Caucci, Serena; Egli, Andrea; Bürgmann, Helmut



Increasing streamflow forecast lead time for snowmelt-driven catchment based on large-scale climate patterns  

NASA Astrophysics Data System (ADS)

This study focuses on improving the spring-summer streamflow forecast lead time using large scale climate patterns. An artificial intelligence type data-driven model, Support Vector Machine (SVM), was developed incorporating oceanic-atmospheric oscillations to increase the forecast lead time. The application of SVM model is tested on three unimpaired gages in the North Platte River Basin. Seasonal averages of oceanic-atmospheric indices for the period of 1940-2007 are used to generate spring-summer streamflow volumes with 3-, 6- and 9-month lead times. The results reveal a strong association between coupled indices compared to their individual effects. The best streamflow estimates are obtained at 6-month compared to 3-month and 9-month lead times. The proposed modeling technique is expected to provide useful information to water managers and help in better managing the water resources and the operation of water systems.

Kalra, Ajay; Ahmad, Sajjad; Nayak, Anurag



Increasing Rate of Detection of Wrong-Patient Radiographs: Use of Photographs Obtained at Time of Radiography  

PubMed Central

OBJECTIVE The objective of our study was to evaluate whether facial and chest photographs obtained simultaneously with radiographs increase radiologists’ detection rate of labeling errors. MATERIALS AND METHODS We obtained simultaneous portable radiographs and photographs of 34 patients. We generated 88 pairs of chest radiographs (one recent radiograph, one prior radiograph) and compiled a set of 20 pairs for reader review. Two, three, or four mismatched pairs (i.e., pairs containing radiographs of different patients) were introduced into each list. Ten radiologist readers blinded to the presence of mismatches interpreted the 20 radiograph pairs. Readers then reviewed a second set of 20 pairs containing mismatches but photographs of the patients obtained at the time of imaging were attached to the radiographs. Readers were not instructed regarding the purpose of the photographs. The mismatch detection rate and time for interpretation was recorded for both sessions. The two-tailed Fisher exact test was used to evaluate differences in mismatch detection rates between sessions, with a p value of less than 0.05 being considered significant. RESULTS The error detection rates without (3/24 = 12.5%) and with (16/25 = 64%) photographs significantly differed (p = 0.0003). The average interpretation times without and with photographs were 35.73 and 26.51 minutes, respectively (two-tailed Student t test, p = 0.1165). CONCLUSION The use of photographs increased the detection of errors without a concomitant increase in film interpretation time, which may translate into improvements in patient safety without an increase in interpretation time. PMID:23521477

Tridandapani, Srini; Ramamurthy, Senthil; Galgano, Samuel J.; Provenzale, James M.



Does Assertive Community Treatment Increase Medication Adherence for People With Co-occurring Psychotic and Substance Use Disorders?  

Microsoft Academic Search

OBJECTIVE: This study analyzed data from a randomized trial to examine the impact on medication adherence of integrated treatment delivered via assertive community treatment (ACT) versus standard clinical case management (SCCM). METHOD: Data from the original study included 198 study participants with co-occurring psychotic and substance use disorders who were randomly assigned to receive integrated treatment via ACT or SCCM

Jennifer I. Manuel; Nancy H. Covell; Carlos T. Jackson; Susan M. Essock



Hydrothermal treatment coupled with mechanical expression at increased temperature for excess sludge dewatering: influence of operating conditions and the process energetics.  


Dewatering is very important for excess sludge treatment and disposal. Hydrothermal treatment coupled with mechanical expression is a novel technology, in which a conventional pressure dewatering is combined with hydrothermal effect to realize an improved liquid/solids separation with low energy consumption. In this study, the process was performed by way of that the excess sludge was hydrothermally treated first and then the mechanical expression was employed immediately at increased temperature in two separate cells respectively. The results demonstrated that the mechanical expression employed at increased temperature showed a significant advantage than that at room temperature, given a further reduction of 19-47% of the moisture content. The dewatering process at room temperature was mostly depended on the effect of mechanical expression. Hydrothermal process, more importantly than mechanical effect at increased temperatures, seemed to govern the extent to which the dewatering process occurred. The dewatering began to show a positive effect when the temperature was exceeded the threshold temperature (between 120 and 150 °C). The residence time of 30 min promoted a substantial conversion in the sludge surface properties. After dewatering at temperatures of 180-210 °C, the moisture content decreased from 52 to 20% and the corresponding total water removal as filtrate was between 81 and 93%. It was observed that the moisture content of filter cake correlated with surface charge (Rp = -0.93, p < 0.05) and relative hydrophobicity (Rp = -0.99, p < 0.05). The calculated energy balance suggested that no additional external energy input is needed to support the dewatering process for excess sludge. The dewatering process needs an obviously lower energy input compared to thermal drying and electro-dewatering to produce a higher solids content cake. PMID:25090626

Wang, Liping; Zhang, Lei; Li, Aimin



Treatment with afobazole at delayed time points following ischemic stroke improves long-term functional and histological outcomes.  


There is currently a significant lack of therapeutic options for acute ischemic stroke, and no drug has been approved for treating patients at delayed time points (?6h post-stroke). Afobazole, an anxiolytic currently used clinically in Russia, has been shown to reduce neuronal and glial cell injury in vitro following ischemia. Experiments using the permanent middle cerebral artery occlusion (MCAO) rat model were carried out to determine if afobazole can reduce ischemic stroke damage in vivo and expand the therapeutic window for stroke treatment. Post-stroke (24h) application of afobazole (0.3-3mg/kg) significantly decreased infarct volume at 96h post-surgery, as determined by Fluoro-Jade and NeuN staining of brain sections. Moreover, afobazole helped preserve both the levels and normal histological distribution of myelin basic protein, indicating a reduction in white matter injury. A time-dependence study showed that either pre-treatment or treatment started 6 to 48h post-stroke with the drug yields improved outcomes at 96h. The decrease in infarct volume produced by afobazole was blocked by the application of either a ?-1 (BD 1063, 30mg/kg) or a ?-2 (SM-21, 1mg/kg) antagonist, indicating that both receptor subtypes are involved in the effects of afobazole. Treatment with afobazole starting at 24h post-stroke resulted in enhanced survival one month following surgery. Behavioral testing of animals 28-32days post-surgery using the elevated body swing and forelimb grip-strength tests revealed that treatment with afobazole starting 24h post-stroke significantly reduces behavioral deficits caused by ischemic stroke. The increase in survival and improved functional outcomes are accompanied by a reduction in infarct volume, as determined by thionin staining of brain sections. Taken together, our data support the use of afobazole as a post-stroke pharmacological agent to expand the current therapeutic window. PMID:24141021

Katnik, C; Garcia, A; Behensky, A A; Yasny, I E; Shuster, A M; Seredenin, S B; Petrov, A V; Seifu, S; McAleer, J; Willing, A; Cuevas, J



Temporal trends of time to antiretroviral treatment initiation, interruption and modification: examination of patients diagnosed with advanced HIV in Australia  

PubMed Central

Introduction HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Methods We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Results Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural–regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007–2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007–2012 versus 1996–2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusions Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods. PMID:25865372

Wright, Stephen T; Law, Matthew G; Cooper, David A; Keen, Phillip; McDonald, Ann; Middleton, Melanie; Woolley, Ian; Kelly, Mark; Petoumenos, Kathy



The Immediate Effect of Neuromuscular Joint Facilitation (NJF) Treatment on Electromechanical Reaction Times of Hip Flexion.  


[Purpose] The aim of this study was to investigate the change in electromechanical reaction times (EMG-RT) of hip flexion of younger persons after neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 39 healthy young people, who were divided into two groups: a NJF group and a proprioceptive neuromuscular facilitation (PNF) group. The NJF group consisted of 16 subjects (7 males, 9 females), and the PNF group consisted of 23 subjects (10 males, 13 females). [Methods] Participants in the NJF group received NJF treatment. We measured the EMG-RT, the premotor time (PMT) and the motor time (MT) during hip flexion movement before and after the intervention in both groups. [Results] There were no significant differences among the results of the PNF group. For the NJF group, there were significant differences in PMT and EMG-RT after NJF treatment. [Conclusion] These results suggest that there is an immediate effect of NJF intervention on electromechanical reaction times of hip flexion. PMID:24396211

Huo, Ming; Wang, Hongzhao; Ge, Meng; Huang, Qiuchen; Li, Desheng; Maruyama, Hitoshi



On board short-time high temperature heat treatment of ballast water: a field trial under operational conditions.  


A ballast water short-time high temperature heat treatment technique was applied on board a car-carrier during a voyage from Egypt to Belgium. Ballast water from three tanks was subjected for a few seconds to temperatures ranging from 55 degrees C to 80 degrees C. The water was heated using the vessel's heat exchanger steam and a second heat exchanger was used to pre-heat and cool down the water. The treatment was effective at causing mortality of bacteria, phytoplankton and zooplankton. The International Maritime Organization (IMO) standard was not agreed before this study was carried out, but comparing our results gives a broad indication that the IMO standard would have been met in some of the tests for the zooplankton, in all the tests for the phytoplankton; and probably on most occasions for the bacteria. Passing the water through the pump increased the kill rate but increasing the temperature above 55 degrees C did not improve the heat treatment's efficacy. PMID:18036619

Quilez-Badia, Gemma; McCollin, Tracy; Josefsen, Kjell D; Vourdachas, Anthony; Gill, Margaret E; Mesbahi, Ehsan; Frid, Chris L J



The effects of increasing body mass index on heartburn severity, frequency and response to treatment with dexlansoprazole or lansoprazole  

PubMed Central

Background Higher body mass index (BMI) is a recognised risk factor for gastro-oesophageal reflux disease (GERD). Data regarding the impact of BMI on proton pump inhibitor (PPI) therapy are conflicting. Aim To assess the impact of BMI on baseline heartburn symptom severity and frequency and response to PPI therapy in patients with non-erosive GERD (NERD) or erosive oesophagitis (EO). Methods In post hoc analyses of phase 3 trial data, 621 NERD and 2692 EO patients were stratified by BMI (<25, 25 to <30 and ?30 kg/m2). NERD patients received either dexlansoprazole MR 30 mg or placebo daily for 4 weeks. EO patients received either dexlansoprazole MR 60 mg or lansoprazole 30 mg for 8 weeks. Symptom frequency and severity were assessed at baseline and subsequently by daily diary. Results In both the NERD and EO cohorts, baseline heartburn severity increased with increasing BMI. The impact of PPI therapy on the reduction in heartburn symptom frequency and severity in both NERD and EO patients was similar across BMI categories. EO healing rates in patients treated with dexlansoprazole but not lansoprazole were higher in obese patients compared with those with a BMI <30 kg/m2. Differences between the PPIs were small. Conclusions The PPIs evaluated in this study reduced the frequency and severity of 24-h heartburn regardless of baseline BMI. In addition, because patients with higher BMI have more severe symptoms at baseline, they may experience greater therapeutic gain with dexlansoprazole (NERD and erosive oesophagitis) and possibly lansoprazole (erosive oesophagitis) treatment. PMID:23451835

Peura, D A; Pilmer, B; Hunt, B; Mody, R; Perez, M C



GPU-accelerated ray-tracing for real-time treatment planning  

NASA Astrophysics Data System (ADS)

Dose calculation methods in radiotherapy treatment planning require the radiological depth information of the voxels that represent the patient volume to correct for tissue inhomogeneities. This information is acquired by time consuming ray-tracing-based calculations. For treatment planning scenarios with changing geometries and real-time constraints this is a severe bottleneck. We implemented an algorithm for the graphics processing unit (GPU) which implements a ray-matrix approach to reduce the number of rays to trace. Furthermore, we investigated the impact of different strategies of accessing memory in kernel implementations as well as strategies for rapid data transfers between main memory and memory of the graphics device. Our study included the overlapping of computations and memory transfers to reduce the overall runtime using Hyper-Q. We tested our approach on a prostate case (9 beams, coplanar). The measured execution times for a complete ray-tracing range from 28 msec for the computations on the GPU to 99 msec when considering data transfers to and from the graphics device. Our GPU-based algorithm performed the ray-tracing in real-time. The strategies efficiently reduce the time consumption of memory accesses and data transfer overhead. The achieved runtimes demonstrate the viability of this approach and allow improved real-time performance for dose calculation methods in clinical routine.

Heinrich, H.; Ziegenhein, P.; Kamerling, C. P.; Froening, H.; Oelfke, U.



Plasma Gelsolin Levels Decrease in Diabetic State and Increase upon Treatment with F-Actin Depolymerizing Versions of Gelsolin  

PubMed Central

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care. PMID:25478578

Khatri, Neeraj; Sagar, Amin; Peddada, Nagesh; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Veena; Ashish



Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment  

PubMed Central

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs. PMID:25238411

Tierney, Dylan B.; Franke, Molly F.; Becerra, Mercedes C.; Alcántara Virú, Félix A.; Bonilla, César A.; Sánchez, Epifanio; Guerra, Dalia; Muñoz, Maribel; Llaro, Karim; Palacios, Eda; Mestanza, Lorena; Hurtado, Rocío M.; Furin, Jennifer J.; Shin, Sonya; Mitnick, Carole D.



[Time course of changes in gustatory function test results and subjective symptoms, and predictive factors for response in patients with taste disorder receiving 24-week zinc replacement treatment].  


In a taste disorder, an agreement between patients' complaints and gustatory function test results is not necessarily found both at the initial hospital visit and during the course of treatment; therefore, it is difficult to assess treatment responses and review treatment strategies based on the assessed treatment responses. The present study investigated the time course of changes in disc gustometry results and subjective symptom scores measured at 4-week intervals in 44 patients with a taste disorder who were considered eligible for zinc replacement treatment and who received polaprezinc at a dose of 150 mg/day (equivalent to a 34 mg/day dose of zinc) for up to 24 weeks. The study also examined the potential differences in treatment outcomes according to the predictive factors for response such as patient background and assessed disc gustometry results during the course of treatment. Results indicated that disc gustometry results and subjective symptom scores showed different time courses of changes. The response rate as measured by disc gustometry was 47.7% at week 12 of treatment, and showed a subsequent slow increase to 56.8% at week 24. On the other hand, subjective symptom scores showed a time-proportional improvement up to week 24. Among the patients included in the present study, a clear difference was found according to the presence or absence of an improving trend as determined by disc gustometry at week 12 of treatment, although there were no differences in ultimate treatment responses, including categories of taste disorder, according to patient background. Patients showing a trend toward improvement had significantly better treatment responses in terms of both ultimate response rates and subjective symptom scores, whereas patients showing no trend toward improvement were less likely to respond to the subsequent 12-week continued treatment. PMID:25255648

Sakagami, Masafumi; Kurono, Yuichi; Inokuchi, Akira; Takeda, Noriaki; Aiba, Tsunemasa; Nin, Tomomi; Ikeda, Minoru