Explore the vast range of titles available.

Offers a complete ranking of United States presidents from best to worst based on their leadership skills, moral authority, and ability to persuade the public.

Background “Live tissue training” (LTT) is simulation that uses a live anaesthetised animal in place of a human patient. It is a training practice which is significantly contested, but continues to occur despite availability of alternative simulator models. The aim of this study was to explore if, and how, medical professionals who participate in LTT justify their own professional involvement. Methods Fifteen semi-structured interviews of physicians who had knowledge and prior experience of LTT were performed as part of a wider research project and initially analysed using the Framework Method. Data categorised as ‘ethical views’ underwent a secondary thematic analysis to answer this research aim. Data were grouped by similar meaning to produce themes in the form of beliefs or views expressed by the participants. Results Although no participant used language to explicitly indicate moral theorising, there is a set of identifiable coherent beliefs/views among the cohort. A belief that training must be conducted in order to save human patients’ lives (1); that human life is of higher value than animal life (2); and that there is no sufficiently good alternative to LTT (3). It is felt that LTT is reasonable as the numbers of animals used are minimised and opportunities for learning or other uses maximised (4); animals are well cared for and are not suffering (5) and reasonable in comparison to other animal uses (6). Conclusion There is a predominant consequentialist thinking regarding the use of live animals, with evidence that the 3Rs principles are being considered, if not explicitly, as a restriction on the use of animals for LTT and also partly to justify or defend medical professionals’ involvement. We suggest that professional identity is likely to have a role in forming these justificatory arguments, but personal views about the moral standing of animals and notions of speciesism could also influence decisions about being involved in LTT.

Estimating production and loss rates of cell populations is essential but difficult. The current state-of-the-art method to estimate these rates involves mathematical modelling of deuterium labelling experiments. Current models typically assume that the labelling in the precursors of the population of interest (POI) is proportional to the deuterium enrichment in body water/glucose. This assumption is not always true and it is known that this can have a significant effect on the rates estimated from labelling experiments. Here we quantify the effect that different turnover (replacement) rates of the precursors can have on the estimated proliferation and loss rates of a POI by explicitly modelling the dynamics of the precursors. We first confirm earlier results that the labelling curve of the POI only reflects its own turnover rate if either the turnover rate of the precursors is sufficiently fast, or the contribution from the precursors is sufficiently small. Next, we describe three realistic scenarios with a slowly turning over precursor population, and show how this changes the interpretation of the different parameter estimates. Our analyses underpin that uniquely identifying the turnover rate of a POI requires measurements (or knowledge) on the turnover of its immediate precursors.

Background This report describes the authors’ experience with a unique endoluminal, endoscopically delivered and retrieved gastroduodenojejunal bypass sleeve, including short-term weight loss and changes in comorbidities. Methods A prospective, single-center trial was designed. The patients were morbidly obese individuals who met the National Institutes of Health criteria for bariatric surgery. The device used was a unique gastroduodenojejunal bypass sleeve secured at the esophagogastric junction with endoscopic and laparoscopic techniques and designed to create an endoluminal gastroduodenojejunal bypass. At completion of the trial, the device was explanted with endoscopic retrieval. The primary end points were safety and incidence of adverse events. The secondary outcomes included the percentage of excess weight loss and changes in comorbidities, specifically glucose control, use of antihyperglycemic medications, and changes in hemoglobin A1c levels. Results From July 2008 to February 2010, 24 patients were enrolled in the trial. The gastroduodenojejunal bypass sleeve was implanted, left in situ, and then retrieved. The 7 men and 17 women in the study had a mean preoperative body mass index of 42 kg/m 2 . The device was successfully delivered in 22 of the 24 patients (92%) and retrieved endoscopically from all 22 patients in whom it was implanted (100%). Two patients were excluded from the study preprocedurally. The one patient was excluded preoperatively due to noncompliance with the preoperative liquid diet. For the other excluded patient, the device was not attempted endoscopically due to significant inflammation at the gastroesophageal junction at the time of laparoscopic evaluation. Of the 22 patients who had the device implanted, 17 maintained it (77%) and completed the full 12-week trial. These patients had 39.7% excess weight loss at completion of the study. The primary reason for early explantation of the device was early postoperative dysphagia. The seven patients with preoperative diabetes mellitus all had normal blood glucose levels throughout the trial, and none required antihyperglycemic medications. All four patients with elevated hemoglobin A1c levels preoperatively showed improvement by the end of the trial. Conclusions This trial demonstrated that the endoluminal gastroduodenojejunal sleeve can achieve excellent weight loss at 12 weeks. No patient safety issues were encountered. Adverse effects were minimal and resolved at endoscopic device removal. Effective glycemic control was demonstrated through use of the device during the trial. Long-term results are needed.

The ability to associate environmental stimuli with positive outcomes is a fundamental form of learning. While extensive research has focused on midbrain dopamine neurons during associative learning, less is known about learning-mediated changes in the afferents that shape dopamine neuron responses. We demonstrate in rats that during critical phases of learning, anion homeostasis in midbrain inhibitory GABA neurons – a primary source of input to dopamine neurons – is disrupted due to downregulation of the potassium chloride cotransporter KCC2. This alteration in GABA neurons preferentially impacted lateral mesoaccumbal dopamine pathways and was not observed after learning was established. At the network level, learning-mediated KCC2 downregulation was associated with enhanced synchronization between individual GABA neurons and increased dopamine responses to rewards and reward-related stimuli. Conversely, enhancing KCC2 function during learning reduced GABA synchronization, diminished relevant dopamine signaling, and prevented cue-reward associations. Thus, circuit-specific adaptations in midbrain GABA neurons are crucial for forming new reward-related behaviors. In this study, the authors show that during reward learning, transient loss of chloride transport enhances midbrain GABA network synchronization and dopamine signaling, changes essential for forming new reward-related memories.

Introduction Here, we report the first series of patients with 1-year implantation of a novel, endoluminal, endoscopically delivered and retrieved gastro-duodeno-jejunal bypass sleeve (GJBS) (ValenTx, Inc. Carpinteria, CA, USA). In this report, we present the safety, feasibility of the device, weight loss, and changes in comorbidities. Methods and procedures A prospective, single-center, 12-month trial was designed. The patients are morbidly obese individuals who meet the NIH criteria for bariatric surgery. The GJBS is a 120-cm sleeve secured at the esophago-gastric junction with endoscopic and laparoscopic techniques that is designed to create an endoluminal gastro-duodeno-jejunal bypass. The device was implanted and, at the completion of the trial, retrieved with an endoscopic technique. The primary endpoints were safety and incidence of adverse events. The secondary outcomes included the percentage of excess weight loss (EWL) and changes in comorbidities, specifically glucose control, use of antihyperglycemics, and changes in hemoglobin A1C levels. Results From July 2009 until October 2009, 13 patients were prospectively enrolled for the 1-year trial. The study included five men and eight women with a mean preoperative BMI of 42 kg/m 2 . One patient was excluded, at the time of endoscopic evaluation, due to inflammation at the GE junction. Two additional patients required early explantation of the device, within the first 4 weeks, due to patient intolerance. Upon explant of the device, both patients’ symptoms improved. In the remaining ten patients, the device was implanted, left in situ for 12 months, and then retrieved endoscopically. Safe delivery of the cuff at the gastro-esophageal junction was seen in all ten patients whom had device implants, without complication. No esophageal leak was seen immediately post-procedure or during follow-up. The sleeve device was well tolerated within the bowel lumen during the 12-month study, specifically, no bowel erosions, ulceration, or pancreatitis was observed. All ten patients reached the 1-year mark. Of the ten, six had fully attached and functional devices throughout the follow-up, verified by endoscopy. The mean percentage EWL, at 1 year, in this group was 54 %. In the remaining four patients, partial cuff detachment was observed at follow-up endoscopy. The percentage EWL was lower in this group. Of the six patients that reached a year with a fully attached device, five were followed at an average of 14-months post-explant (26 months from the time of device implant). These five maintained an average percentage EWL of 30 % at the 14-month post-explant follow-up. Co-morbidites measured included diabetes mellitus, hypertension, hyperlipidemia, and use of antihyperglycemics. Each of the measured comorbidities showed improvement during the 12-month trial. Discussion The endoluminal, GJBS can be safely placed and retrieved. The short-term data show it is well tolerated with a good safety profile. It achieves excellent weight loss results with over 70 % of all comorbidities resolved or significantly improved.

Tissue-resident memory T cells (T RM ) protect from repeat infections within organs and barrier sites. The breadth and duration of such protection are defined at minimum by three quantities: the rate at which new T RM are generated from precursors, their rate of self-renewal, and their rate of loss through death, egress, or differentiation. Quantifying these processes individually is challenging. Here we combine genetic fate mapping tools and mathematical models to untangle these basic homeostatic properties of CD4 + T RM in the skin and gut lamina propria (LP) of healthy adult mice. We show that CD69 + CD4 + T RM in skin reside for ∼24 days and self-renew more slowly, such that clones halve in size approximately every 5 weeks, and approximately 2% of cells are replaced daily from precursors. CD69 + CD4 + T RM in LP have shorter residencies (∼14 days) and are maintained largely by immigration (4–6% per day). We also find evidence that the continuous replacement of CD69 + CD4 + T RM at both sites derives from circulating effector-memory CD4 + T cells, in skin possibly via a local CD9 − intermediate. Our approach maps the ontogeny of CD4 + T RM in skin and LP and exposes their dynamic and distinct behaviours, with continuous seeding and erosion potentially impacting the duration of immunity at these sites.

High nitrogen (N) rate often leads to low yield of rice due to lodging and mutual shading. This study was conducted to ascertain whether silicon (Si) could enhance yield response of rice to higher N rate by enhancing rigidity of plant parts and improving photosynthesis. The effects of Si and N on crop growth, photosynthesis, N use efficiencies and yield of rice were investigated during wet season (June to November) in sub‐humid tropical region of India. An increasing trend in crop growth rate with Si at all levels of N was observed. Silicon reduced the flag leaf angle making the leaf more upright and enhanced flag leaf N content. Leaf chlorophyll concentration and single leaf photosynthesis rate were higher with Si compared to without Si at flowering stage. Both N and Si significantly affected panicle number and grain filling. Application of 200 kg SiO2 ha−1 and 100 kg N ha−1 produced the highest number of panicle per square meter, filled grain per panicle and yield. Significant yield increases ranging from 8.2–16.9% were observed with Si compared to without Si. Both N and Si treatments had significant effects on N uptake and N use efficiency. Agronomic N use efficiency and N recovery efficiency were higher with Si compared to without Si. The highest physiological N use efficiency was recorded with 200 kg SiO2 ha−1 and 80 kg N ha−1. Silicon may enhance yield response of rice to higher N rate by improving source (photosynthetic) capacity and sink (reproductive organ) strength.

The fact that T-cell numbers remain relatively stable throughout life, and that T-cell proliferation rates increase during lymphopenia, has led to the consensus that T-cell numbers are regulated in a density-dependent manner. Competition for resources among memory T cells has been proposed to underlie this ‘homeostatic’ regulation. We first review how two classic models of resource competition affect the T-cell receptor (TCR) diversity of the memory T-cell pool. First, ‘global’ competition for cytokines leads to a skewed repertoire that tends to be dominated by the very first immune response. Second, additional ‘cognate’ competition for specific antigens results in a very diverse and stable memory T-cell pool, allowing every antigen to be remembered, which we therefore define as the ‘gold-standard’. Because there is limited evidence that memory T cells of the same specificity compete more strongly with each other than with memory T cells of different specificities, i.e., for ‘cognate’ competition, we investigate whether cellular aging could account for a similar level of TCR diversity. We define cellular aging as a declining cellular fitness due to reduced proliferation. We find that the gradual erosion of previous T-cell memories due to cellular aging allows for better establishment of novel memories and for a much higher level of TCR diversity compared to global competition. A small continual source (either from stem-cell-like memory T-cells or from naive T-cells due to repeated antigen exposure) improves the diversity of the memory T-cell pool, but remarkably, only in the cellular aging model. We further show that the presence of a source keeps the inflation of chronic memory responses in check by maintaining the immune memories to non-chronic antigens. We conclude that cellular aging along with a small source provides a novel and immunologically realistic mechanism to achieve and maintain the ‘gold-standard’ level of TCR diversity in the memory T-cell pool.

Nutrient management in resource conservation practices influence the structural and functional microbial diversities and thereby affect biological processes and biochemical properties in soil. We studied the long-term effects of resource conservation technologies on functional microbial diversity and their interactions with soil biochemical properties and enzymatic activities in tropical rice-green gram cropping system. The experiment includes seven treatments viz., conventional practice (CC), brown manuring (BM), green manuring (GM), wet direct drum sowing, zero tillage, green manuring-customized leaf colour chart based-N application (GM-CLCC-N) and biochar (BC) application. The result of the present study revealed that microbial biomass nitrogen (N), carbon (C) and phosphorus (P) in GM practice were increased by 23.3, 37.7 and 35.1%, respectively than CC. GM, BM and GM-CLCC-N treatments provide higher yields than conventional practice. The average well color development value, Shannon index and McIntosh index were significantly higher by 26.6%, 86.9% and 29.2% in GM as compared to control treatment. So, from this study we can conclude that resource conservation practices like GM, GM-CLCC N and BM in combination with chemical fertilizers provide easily decomposable carbon source to support the microbial growth. Moreover, dominance of microbial activity in biomass amended treatments (GM, GM-CLCC N and BM) indicated that these treatments could supply good amount of labile C sources on real time basis for microbial growth that may protect the stable C fraction in soil, hence could support higher yield and soil organic carbon build-up in long run under rice-green gram soil.