Time trends in service provision and survival outcomes for patients with renal cancer treated by nephrectomy in England 2000-2010.

OBJECTIVE: To describe the temporal trends in nephrectomy practice and outcomes for English patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Adult RCC nephrectomy patients treated between 2000 and 2010 were identified in the National Cancer Data Repository and Hospital Episode Statistics, and followed-up until date of death or 31 December 2015 (n = 30 763). We estimated the annual frequency for each nephrectomy type, the hospital and surgeon numbers and their case volumes. We analysed short-term surgical outcomes, as well as 1- and 5-year relative survivals. RESULTS: Annual RCC nephrectomy number increased by 66% during the study period. Hospital number decreased by 24%, whilst the median annual hospital volume increased from 10 to 23 (P < 0.01). Surgeon number increased by 27% (P < 0.01), doubling the median consultant number per hospital. The proportion of minimally invasive surgery (MIS) nephrectomies rose from 1% to 46%, whilst the proportion of nephron-sparing surgeries (NSS) increased from 5% to 16%, with 29% of all T1 disease treated with partial nephrectomy in 2010 (P < 0.01). The 30-day mortality rate halved from 2.4% to 1.1% and 90-day mortality decreased from 4.9% to 2.6% (P < 0.01). The 1-year relative survival rate increased from 86.9% to 93.4%, whilst the 5-year relative survival rate rose from 68.2% to 81.2% (P < 0.01). Improvements were most notable in patients aged ≥65 years and those with T3 and T4 disease. CONCLUSIONS: Surgical RCC management has changed considerably with nephrectomy centralisation and increased NSS and MIS. In parallel, we observed significant improvements in short- and long-term survival particularly for elderly patients and those with locally advanced disease

Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest

Large mammals that live in arid and/or desert environments can cope with seasonal and local variations in rainfall, food and climate1 by moving long distances, often without reliable water or food en route. The capacity of an animal for this long-distance travel is substantially dependent on the rate of energy utilization and thus heat production during locomotion—the cost of transport2,3,4. The terrestrial cost of transport is much higher than for flying (7.5 times) and swimming (20 times)4. Terrestrial migrants are usually large1,2,3 with anatomical specializations for economical locomotion5,6,7,8,9, because the cost of transport reduces with increasing size and limb length5,6,7. Here we used GPS-tracking collars10 with movement and environmental sensors to show that blue wildebeest (Connochaetes taurinus, 220 kg) that live in a hot arid environment in Northern Botswana walked up to 80 km over five days without drinking. They predominantly travelled during the day and locomotion appeared to be unaffected by temperature and humidity, although some behavioural thermoregulation was apparent. We measured power and efficiency of work production (mechanical work and heat production) during cyclic contractions of intact muscle biopsies from the forelimb flexor carpi ulnaris of wildebeest and domestic cows (Bos taurus, 760 kg), a comparable but relatively sedentary ruminant. The energetic costs of isometric contraction (activation and force generation) in wildebeest and cows were similar to published values for smaller mammals. Wildebeest muscle was substantially more efficient (62.6%) than the same muscle from much larger cows (41.8%) and comparable measurements that were obtained from smaller mammals (mouse (34%)11 and rabbit (27%)). We used the direct energetic measurements on intact muscle fibres to model the contribution of high working efficiency of wildebeest muscle to minimizing thermoregulatory challenges during their long migrations under hot arid conditions

Investigating preferences for mosquito-control technologies in Mozambique with latent class analysis

<p>Abstract</p> <p>Background</p> <p>It is common practice to seek the opinions of future end-users during the development of innovations. Thus, the aim of this study is to investigate latent classes of users in Mozambique based on their preferences for mosquito-control technology attributes and covariates of these classes, as well as to explore which current technologies meet these preferences.</p> <p>Methods</p> <p>Surveys were administered in five rural villages in Mozambique. The data were analysed with latent class analysis.</p> <p>Results</p> <p>This study showed that users' preferences for malaria technologies varied, and people could be categorized into four latent classes based on shared preferences. The largest class, constituting almost half of the respondents, would not avoid a mosquito-control technology because of its cost, heat, odour, potential to make other health issues worse, ease of keeping clean, or inadequate mosquito control. The other three groups are characterized by the attributes which would make them avoid a technology; these groups are labelled as the bites class, by-products class, and multiple-concerns class. Statistically significant covariates included literacy, self-efficacy, willingness to try new technologies, and perceived seriousness of malaria for the household.</p> <p>Conclusions</p> <p>To become widely diffused, best practices suggest that end-users should be included in product development to ensure that preferred attributes or traits are considered. This study demonstrates that end-user preferences can be very different and that one malaria control technology will not satisfy everyone.</p

End of life care interventions for people with dementia in care homes : addressing uncertainty within a framework for service delivery and evaluation

© 2015 Goodman et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedMethods: The data from three studies on EoL care in care homes: (i) EVIDEM EoL , (ii) EPOCH , and (iii) TTT EoL were used to inform the development of the framework. All used mixed method designs and two had an intervention designed to improve how care home staff provided end of life care. The EVIDEM EoL and EPOCH studies tracked the care of older people in care homes over a period of 12 months. The TTT study collected resource use data of care home residents for three months, and surveyed decedents' notes for ten months, Results: Across the three studies, 29 care homes, 528 residents, 205 care home staff, and 44 visiting health care professionals participated. Analysis of showed that end of life interventions for people with dementia were characterised by uncertainty in three key areas; what treatment is the 'right' treatment, who should do what and when, and in which setting EoL care should be delivered and by whom? These uncertainties are conceptualised as Treatment uncertainty, Relational uncertainty and Service uncertainty. This paper proposes an emergent framework to inform the development and evaluation of EoL care interventions in care homes. Conclusion: For people with dementia living and dying in care homes, EoL interventions need to provide strategies that can accommodate or "hold" the inevitable and often unresolvable uncertainties of providing and receiving care in these settingsPeer reviewe

Win-Win for Wind and Wildlife: A Vision to Facilitate Sustainable Development

Wind energy offers the potential to reduce carbon emissions while increasing energy independence and bolstering economic development. However, wind energy has a larger land footprint per Gigawatt (GW) than most other forms of energy production, making appropriate siting and mitigation particularly important. Species that require large unfragmented habitats and those known to avoid vertical structures are particularly at risk from wind development. Developing energy on disturbed lands rather than placing new developments within large and intact habitats would reduce cumulative impacts to wildlife. The U.S. Department of Energy estimates that it will take 241 GW of terrestrial based wind development on approximately 5 million hectares to reach 20% electricity production for the U.S. by 2030. We estimate there are ∼7,700 GW of potential wind energy available across the U.S., with ∼3,500 GW on disturbed lands. In addition, a disturbance-focused development strategy would avert the development of ∼2.3 million hectares of undisturbed lands while generating the same amount of energy as development based solely on maximizing wind potential. Wind subsidies targeted at favoring low-impact developments and creating avoidance and mitigation requirements that raise the costs for projects impacting sensitive lands could improve public value for both wind energy and biodiversity conservation

Idiopathic radiographic apical root resorption in wind instrument players

Root resorption of the permanent teeth involves an elaborate interaction among inflammatory cells resulting in loss of dental hard tissues. This report describes three clinical cases where idiopathic root resorption occurred in wind instrument playing patients. These patients produce adequate non-orthodontic forces, while playing their instruments, to expose their teeth to root resorbing force. Careful clinical monitoring of patients' teeth should be undertaken, as the additive effects of orthodontic treatment and musical habits are unknown

Stereoselective handling of perhexiline:Implications regarding accumulation within the human myocardium

Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (−) perhexiline may selectively modulate heart rate reduction

Ryanodine receptor leak triggers fiber Ca²⁺ redistribution to preserve force and elevate basal metabolism in skeletal muscle

Muscle contraction depends on tightly regulated Ca2+ release. Aberrant Ca2+ leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca2+ leak drives these pathologies is unknown. Here, we investigate the effects of four mouse genotypes with increasingly severe RyR1 leak in skeletal muscle fibers. We find that RyR1 Ca2+ leak initiates a cascade of events that cause precise redistribution of Ca2+ among the SR, cytoplasm, and mitochondria through altering the Ca2+ permeability of the transverse tubular system membrane. This redistribution of Ca2+ allows mice with moderate RyR1 leak to maintain normal function; however, severe RyR1 leak with RYR1 mutations reduces the capacity to generate force. Our results reveal the mechanism underlying force preservation, increased ATP metabolism, and susceptibility to MH in individuals with gain-of-function RYR1 mutations

Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer

Background Suppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors. Methods SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period. Results SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression. Conclusion Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer