Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a 'monoclonal nose', glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a 'monoclonal nose' and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas. METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed. RESULTS: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis. CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR

A Computational Approach for Designing Tiger Corridors in India

Wildlife corridors are components of landscapes, which facilitate the movement of organisms and processes between intact habitat areas, and thus provide connectivity between the habitats within the landscapes. Corridors are thus regions within a given landscape that connect fragmented habitat patches within the landscape. The major concern of designing corridors as a conservation strategy is primarily to counter, and to the extent possible, mitigate the effects of habitat fragmentation and loss on the biodiversity of the landscape, as well as support continuance of land use for essential local and global economic activities in the region of reference. In this paper, we use game theory, graph theory, membership functions and chain code algorithm to model and design a set of wildlife corridors with tiger (Panthera tigris tigris) as the focal species. We identify the parameters which would affect the tiger population in a landscape complex and using the presence of these identified parameters construct a graph using the habitat patches supporting tiger presence in the landscape complex as vertices and the possible paths between them as edges. The passage of tigers through the possible paths have been modelled as an Assurance game, with tigers as an individual player. The game is played recursively as the tiger passes through each grid considered for the model. The iteration causes the tiger to choose the most suitable path signifying the emergence of adaptability. As a formal explanation of the game, we model this interaction of tiger with the parameters as deterministic finite automata, whose transition function is obtained by the game payoff.Comment: 12 pages, 5 figures, 6 tables, NGCT conference 201

Biliary stenting in patients with pancreatic cancer: results from a population-based cohort study

We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort.We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice.Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed.Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice

Nonhospice Palliative Care Within the Treatment of End‐Stage Liver Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155544/1/hep31226.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155544/2/hep31226_am.pd

Chemotherapy in patients with unresected pancreatic cancer in Australia: A population-based study of uptake and survival

1 Aim Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. 2 Methods We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. 3 Results Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service‐related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors. 4 Conclusions These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa

Background: Nigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health–funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. Methods: This is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. Results: As part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. Conclusions: Our trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa

Dynamics of direct inter-pack encounters in endangered African wild dogs

Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging