Patient needs in advanced Renal Cell Carcinoma: What are patients’ priorities and how well are we meeting them?

Treatment options and duration of therapy for patients with metastatic renal cell carcinoma (mRCC) have increased. Many patients now spend in excess of 2 years on active therapy. These patients’ needs, and the ability of health services to respond to them, are poorly understood. Ten patients living with mRCC for more than 2 years and treated with at least one targeted agent were selected at random from three hospitals in the United Kingdom (UK). One interviewer who was not involved in their care conducted in-depth interviews. Interview transcripts were analysed using Interpretative Phenomenological Analysis (IPA) to identify issues of greatest importance to patients, and to understand how well patients felt their needs were being addressed. Perceived delay in initial diagnosis was a major theme. Being told the truth about treatment side effects upfront was important, but was often at odds with perceived delivery. ‘Dealing with side effects’, understanding dose and its effects and not letting ‘negative thoughts get in’ were highlighted as important, but were highly personal to patients and areas where patients struggled. Concordance was observed with delivery of ‘a clear next step’ for treatment, timely access to drugs and guidance on a drug ‘holiday’. Patient experience of mRCC and its treatment requires a tailored approach. This research suggests there are key opportunities for service improvement and improved communication throughout the pathway to better meet the needs of patients, including non-clinical support to build personal resilience

Patients' experiences of deep brain stimulation for Parkinson's disease: a qualitative systematic review and synthesis.

Published onlineJournal ArticleThis is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVE: To review and synthesise qualitative research studies that have explored patients' experience of deep brain stimulation (DBS) in advanced Parkinson's disease (PD). DESIGN: Systematic review and meta-synthesis of 7 original papers, using metaethnography. SETTING: Studies conducted in Denmark, France and Sweden. PARTICIPANTS: 116 patients who had undergone DBS and 9 spouses of patients. RESULTS: Prior to surgery, the experience of advancing PD is one of considerable loss and a feeling of loss of control. There are significant hopes for what DBS can bring. Following surgery, a sense of euphoria is described by many, although this does not persist and there is a need for significant transitions following this. We suggest that normality as a concept is core to the experience of DBS and that a sense of control may be a key condition for normality. Experience of DBS for patients and spouses, and of the transitions that they must undertake, is influenced by their hopes of what surgery will enable them to achieve, or regain (ie, a new normality). CONCLUSIONS: There is a need for further qualitative research to understand the nature of these transitions to inform how best patients and their spouses can be supported by healthcare professionals before, during and after DBS. In assessing the outcomes of DBS and other treatments in advanced PD, we should consider how to capture holistic concepts such as normality and control. Studies that examine the outcomes of DBS require longer term follow-up.This work was part funded by the Medical Research Council Midland Hub for Trials Methodology Research (Grant Number: G0800808). RG is partially supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula (PenCLAHRC)

Comparison of Titanium® 5 PH- M versus Titanium® 5 plus NUPLURA® PH with the Presence or Absence of Monensin on Health and Performance of Newly Received Feedlot Calves Fed RAMP®

A receiving study was conducted to evaluate the effects of RAMP® with Rumensin® concentration (0 or 25.0 g/ton) given with one of two viral vaccinations (Titanium® 5 PH- M or Titanium® 5 plus NUPLURA® PH) on steer growth performance and morbidity. There were no significant vaccine by diet interactions observed. Neither vaccine treatment nor Rumensin® level affected intake, gain, or feed conversion. Vaccine type did not affect first pull (P = 0.19) or second pull morbidity rates (P = 0.52). These findings suggest that neither vaccine type nor Rumensin® concentration had any effect on steer growth performance or morbidity rate

Predicting aflatoxin content in peanuts using ambient temperature, soil temperature and soil moisture content during pod development

Higher than acceptable aflatoxin levels in peanut kernels (Arachis hypogaea L.) and related products is a worldwide food safety concern. Strict regulatory standards by major importers of peanuts limit the marketability of peanuts for many developing tropical countries including Zambia. The incidence of preharvest aflatoxins is strongly linked to soil and weather conditions during pod-development. This study aimed to formulate statistical models to predict total aflatoxin content in peanut kernels using selected environmental factors during pod development. Field experiments were conducted for two years during which the peanut crop was exposed to 84 combinations of ambient temperature, soil temperature and soil moisture content measured during the last 30 days of pod development. These data were used to formulate regression models to predict total aflatoxin content in peanut kernels. Simple linear regression models had R2 values of 0.30 for maximum ambient temperature, 0.24 for soil temperature and 0.38 for soil moisture content. Combining soil moisture content and soil temperature in a multivariate regression model could explain 54% of the variation in total aflatoxin content while a combination of soil moisture content and maximum ambient temperature could only explain 46% of the variation in total aflatoxin content

Patterns of Natural and Human-Caused Mortality Factors of a Rare Forest Carnivore, the Fisher (Pekania pennanti) in California.

Wildlife populations of conservation concern are limited in distribution, population size and persistence by various factors, including mortality. The fisher (Pekania pennanti), a North American mid-sized carnivore whose range in the western Pacific United States has retracted considerably in the past century, was proposed for threatened status protection in late 2014 under the United States Endangered Species Act by the United States Fish and Wildlife Service in its West Coast Distinct Population Segment. We investigated mortality in 167 fishers from two genetically and geographically distinct sub-populations in California within this West Coast Distinct Population Segment using a combination of gross necropsy, histology, toxicology and molecular methods. Overall, predation (70%), natural disease (16%), toxicant poisoning (10%) and, less commonly, vehicular strike (2%) and other anthropogenic causes (2%) were causes of mortality observed. We documented both an increase in mortality to (57% increase) and exposure (6%) from pesticides in fishers in just the past three years, highlighting further that toxicants from marijuana cultivation still pose a threat. Additionally, exposure to multiple rodenticides significantly increased the likelihood of mortality from rodenticide poisoning. Poisoning was significantly more common in male than female fishers and was 7 times more likely than disease to kill males. Based on necropsy findings, suspected causes of mortality based on field evidence alone tended to underestimate the frequency of disease-related mortalities. This study is the first comprehensive investigation of mortality causes of fishers and provides essential information to assist in the conservation of this species

The Prevalence and Clinical Implications of Comorbid Back Pain in Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

Background:Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty. Purpose/Hypothesis:The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures. Study Design:Cross-sectional study; Level of evidence, 3. Methods:As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients consented to participate in pre- and intraoperative data collection. Demographic characteristics, injury history, preoperative PRO scores, and radiologic and intraoperative findings were recorded for patients undergoing surgical shoulder stabilization. Patients were also asked, whether they had any back pain. Results:The study cohort consisted of 1001 patients (81% male; mean age, 24.1 years). Patients with comorbid back pain (158 patients; 15.8%) were significantly older (28.1 vs 23.4 years; P < .001) and were more likely to be female (25.3% vs 17.4%; P = .02) but did not differ in terms of either preoperative imaging or intraoperative findings. Patients with self-reported back pain had significantly worse preoperative pain and shoulder-related PRO scores (American Shoulder and Elbow Surgeons score, Western Ontario Shoulder Instability Index) (P < .001), more frequent depression (22.2% vs 8.3%; P < .001), poorer mental health status (worse scores for the RAND 36-Item Health Survey Mental Component Score, Iowa Quick Screen, and Personality Assessment Screener) (P < .01), and worse preoperative expectations (P < .01). Conclusion:Despite having similar physical findings, patients with comorbid back pain had more severe preoperative pain and self-reported symptoms of instability as well as more frequent depression and lower mental health scores. The combination of disproportionate shoulder pain, comorbid back pain and mental health conditions, and inferior preoperative expectations may affect not only the patient's preoperative state but also postoperative pain control and/or postoperative outcomes

A Water Resource Management Model, Upper Jordan River Drainage, Utah

As demands upon available water supplies increase within a river basin, there is an accompanying increase in the need to assess the downstream consequences resulting from changes at specific locations within the hydrologic system. This problem is approached in this study by digital computer simulation of the hydrologic system. Modeling concepts are based upon basic relationships which describe the various hydrologic processes. Within a hydrologic system these relationships are linked by the continuity-of-mass principle which requires a mass balance at all points. Spatial resolution is achieved by considering the modeled area as a series of subbasins. The time increment adopted for the model is one month, so that time varying quantities are expressed in terms of mean monthly values. The model is general in nature and is applied to a particular hydrologic system through a programmed verification procedure whereby model coefficients are evaluated for the particular system. In this study the model was applied to the Provo River basin of northern Utah, with emphases being placed upon water rights and operation of storage reservoirs within the system, including Utah Lake. The simulation model consists of three specific parts, namely: (1) parameter optimization; (2) river basin management; and (3) Utah Lake operation. The parameter optimization submodel identifies the model parameters for each subbasin through application of a parameter optimization technique. The river basin management submodel, using the optimized parameters, simulated the hydrologic response of the system to various water resources management alternatives. The Utah Lake operation submodel is linked with the river basin management submodel to comprise a combined Utah Lake operations model. Some comparisons between observed and computed outflow hydrographs at various points within the Provo River basin are shown. The utility of the model for predicting the effects of various possible water resource management alternatives is demonstrated

A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection

Dendritic cells (DCs) are the key initiators of T-helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response. In this study, we show that hepatic DC subsets undergo distinct activation processes in vivo following murine infection with S. mansoni. Conventional DCs (cDCs) from schistosome-infected mice upregulated expression of the costimulatory molecule CD40 and were capable of priming naive CD4+ T cells, whereas plasmacytoid DCs (pDCs) upregulated expression of MHC class II, CD86 and CD40 but were unable to support the expansion of either naive or effector/memory CD4+ T cells. Importantly, in vivo depletion of pDCs revealed that this subset was dispensable for either maintenance or regulation of the hepatic Th2 effector response during acute S. mansoni infection. Our data provides strong evidence that S. mansoni infection favors the establishment of an immunogenic, rather than tolerogenic, liver microenvironment that conditions cDCs to initiate and maintain Th2 immunity in the context of ongoing antigen exposure

West Nile Virus Epidemics in North America Are Driven by Shifts in Mosquito Feeding Behavior

West Nile virus (WNV) has caused repeated large-scale human epidemics in North America since it was first detected in 1999 and is now the dominant vector-borne disease in this continent. Understanding the factors that determine the intensity of the spillover of this zoonotic pathogen from birds to humans (via mosquitoes) is a prerequisite for predicting and preventing human epidemics. We integrated mosquito feeding behavior with data on the population dynamics and WNV epidemiology of mosquitoes, birds, and humans. We show that Culex pipiens, the dominant enzootic (bird-to-bird) and bridge (bird-to-human) vector of WNV in urbanized areas in the northeast and north-central United States, shifted its feeding preferences from birds to humans by 7-fold during late summer and early fall, coinciding with the dispersal of its preferred host (American robins, Turdus migratorius) and the rise in human WNV infections. We also show that feeding shifts in Cx. tarsalis amplify human WNV epidemics in Colorado and California and occur during periods of robin dispersal and migration. Our results provide a direct explanation for the timing and intensity of human WNV epidemics. Shifts in feeding from competent avian hosts early in an epidemic to incompetent humans after mosquito infection prevalences are high result in synergistic effects that greatly amplify the number of human infections of this and other pathogens. Our results underscore the dramatic effects of vector behavior in driving the transmission of zoonotic pathogens to humans