Abstract Many genes have been associated with radiotherapy toxicity, but most have only been found in a single study. Using our cohort of 480 breast cancer patients, we provide replicated evidence ...that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.
Although numerous authors have speculated about permit-value, leasehold interests, and production-input costs above grazing-fee costs, federal policy as to what constitutes property value on federal ...land ranches has never been fully examined. Federal laws and policy were analyzed to determine what basis exists for property rights claims on Western ranches. Laws from the 1800s and 1900s granted split-estate interests in water rights, rights of way, improvements and grazing values. Later statutes provided for the issuance of permits authorizing development of additional improvements, water rights, and rights of way. FLPMA repealed earlier statutes, protected prior rights, and required compensation for ranchers' improvements, water rights, forage, and rights of way when grazing permits are cancelled. Conventional appraisal methods fail to consider highest-and-best use and replacement cost when evaluating split-estate ranches. A five variable valuation model incorporating: (1) water rights, (2) rights of way, (3) range improvements, (4) grazing value, and (5) patented lands, was developed. The model was applied using the case study approach to a controversial ranch in central Nevada. The model, emphasizing highest-and-best use and the replacement cost depreciated approach, was compared to the conventional valuation method that emphasizes sales comparison and income capitalization. The model indicated a fair market value from 4.5 to 150 times greater than that derived from the conventional valuation approach. The difference in values appears primarily due to the failure of conventional appraisal methodology to consider alternative highest-and-best use value of water rights (in this case for quasimunicipal use). Conventional appraisal methods also fail to consider the value of ranchers' range improvements and rights of way associated with the water rights, range improvements and patented lands. It also appears that government regulatory actions may be exerting undue stimulus to create artificially low market values.
We report a significantly-enhanced bioinformatics suite and database for proteomics research called Yale Protein Expression Database（YPED） that is used by investigators at more than 300 institutions ...worldwide. YPED meets the data management, archival, and analysis needs of a high-throughput mass spectrometry-based proteomics research ranging from a singlelaboratory, group of laboratories within and beyond an institution, to the entire proteomics community. The current version is a significant improvement over the first version in that it contains new modules for liquid chromatography–tandem mass spectrometry（LC–MS/MS） database search results, label and label-free quantitative proteomic analysis, and several scoring outputs for phosphopeptide site localization. In addition, we have added both peptide and protein comparative analysis tools to enable pairwise analysis of distinct peptides/proteins in each sample and of overlapping peptides/proteins between all samples in multiple datasets. We have also implemented a targeted proteomics module for automated multiple reaction monitoring（MRM）/selective reaction monitoring（SRM） assay development. We have linked YPED＇s database search results and both label-based and label-free fold-change analysis to the Skyline Panorama repository for online spectra visualization. In addition, we have built enhanced functionality to curate peptide identifications into an MS/MS peptide spectral library for all of our protein database search identification results.
Antarctic krill, Euphausia superba, have a circumpolar distribution but are concentrated within the south-west Atlantic sector, where they support a unique food web and a commercial fishery. Within ...this sector, our first goal was to produce quantitative distribution maps of all six ontogenetic life stages of krill (eggs, nauplii plus metanauplii, calyptopes, furcilia, juveniles, and adults), based on a compilation of all available post 1970s data. Using these maps, we then examined firstly whether "hotspots" of egg production and early stage nursery occurred, and secondly whether the available habitat was partitioned between the successive life stages during the austral summer and autumn, when krill densities can be high. To address these questions, we compiled larval krill density records and extracted data spanning 41 years (1976-2016) from the existing KRILLBASE-abundance and KRILLBASE-length-frequency databases. Although adult males and females of spawning age were widely distributed, the distribution of eggs, nauplii and metanauplii indicates that spawning is most intense over the shelf and shelf slope. This contrasts with the distributions of calyptope and furcilia larvae, which were concentrated further offshore, mainly in the Southern Scotia Sea. Juveniles, however, were strongly concentrated over shelves along the Scotia Arc. Simple environmental analyses based on water depth and mean water temperature suggest that krill associate with different habitats over the course of their life cycle. From the early to late part of the austral season, juvenile distribution moves from ocean to shelf, opposite in direction to that for adults. Such habitat partitioning may reduce intraspecific competition for food, which has been suggested to occur when densities are exceptionally high during years of strong recruitment. It also prevents any potential cannibalism by adults on younger stages. Understanding the location of krill spawning and juvenile development in relation to potentially overlapping fishing activities is needed to protect the health of the south-west Atlantic sector ecosystem.
To investigate whether further centralisation of acute stroke services in Greater Manchester in 2015 was associated with changes in outcomes and whether the effects of centralisation of acute stroke ...services in London in 2010 were sustained.
Retrospective analyses of patient level data from the Hospital Episode Statistics (HES) database linked to mortality data from the Office for National Statistics, and the Sentinel Stroke National Audit Programme (SSNAP).
Acute stroke services in Greater Manchester and London, England.
509 182 stroke patients in HES living in urban areas admitted between January 2008 and March 2016; 218 120 stroke patients in SSNAP between April 2013 and March 2016.
Hub and spoke models for acute stroke care.
Mortality at 90 days after hospital admission; length of acute hospital stay; treatment in a hyperacute stroke unit; 19 evidence based clinical interventions.
In Greater Manchester, borderline evidence suggested that risk adjusted mortality at 90 days declined overall; a significant decline in mortality was seen among patients treated at a hyperacute stroke unit (difference-in-differences -1.8% (95% confidence interval -3.4 to -0.2)), indicating 69 fewer deaths per year. A significant decline was seen in risk adjusted length of acute hospital stay overall (-1.5 (-2.5 to -0.4) days; P<0.01), indicating 6750 fewer bed days a year. The number of patients treated in a hyperacute stroke unit increased from 39% in 2010-12 to 86% in 2015/16. In London, the 90 day mortality rate was sustained (P>0.05), length of hospital stay declined (P<0.01), and more than 90% of patients were treated in a hyperacute stroke unit. Achievement of evidence based clinical interventions generally remained constant or improved in both areas.
Centralised models of acute stroke care, in which all stroke patients receive hyperacute care, can reduce mortality and length of acute hospital stay and improve provision of evidence based clinical interventions. Effects can be sustained over time.
Approximately 23 700 US children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function.
To evaluate neurocognitive ...outcomes of children who survive pediatric intensive care unit (PICU) hospitalization for acute respiratory failure compared with their biological siblings.
Prospective sibling-matched cohort study conducted at 31 US PICUs and associated neuropsychology testing centers. Patients were 8 years or younger with a Pediatric Cerebral Performance Category score of 1 (normal) before PICU admission and less than or equal to 3 (no worse than moderate neurocognitive dysfunction) at PICU discharge, excluding patients with a history of neurocognitive deficits or who were readmitted and underwent mechanical ventilation. Biological siblings were aged 4 to 16 years at testing, with Pediatric Cerebral Performance Category score of 1 and no history of mechanical ventilation or general anesthesia. A total of 121 sibling pairs were enrolled from September 2, 2014, to December 13, 2017, and underwent neurocognitive testing starting March 14, 2015. The date of the final follow-up was November 6, 2018.
Critical illness and PICU treatment for acute respiratory failure.
The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included measures of attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Evaluations occurred 3 to 8 years after hospital discharge.
Patients (n = 121; 55 45% female patients) underwent PICU care at a median (IQR) age of 1.0 (0.2-3.2) years, received a median (IQR) of 5.5 (3.1-7.7) days of invasive mechanical ventilation, and were tested at a median (IQR) age of 6.6 (5.4-9.1) years. Matched siblings (n = 121; 72 60% female siblings) were tested at a median (IQR) age of 8.4 (7.0-10.2) years. Patients had a lower mean estimated IQ than matched siblings (101.5 vs 104.3; mean difference, -2.8 95% CI, -5.4 to -0.2). Among secondary outcomes, patients had significantly lower scores than matched siblings on nonverbal memory (mean difference, -0.9 95% CI, -1.6 to -0.3), visuospatial skills (mean difference, -0.9 95% CI, -1.8 to -0.1), and fine motor control (mean difference, -3.1 95% CI, -4.9 to -1.4) and significantly higher scores on processing speed (mean difference, 4.4 95% CI, 0.2-8.5). There were no significant differences in the remaining secondary outcomes, including attention, verbal memory, expressive language, and executive function.
Among children, survival of PICU hospitalization for respiratory failure and discharge without severe cognitive dysfunction was associated with significantly lower subsequent IQ scores compared with matched siblings. However, the magnitude of the difference was small and of uncertain clinical importance.
Background
Patient and public involvement is required where changes to care provided by the UK National Health Service are proposed. Yet involvement is characterized by ambiguity about its ...rationales, methods and impact.
Aims
To understand how patients and carers were involved in major system changes (MSCs) to the delivery of acute stroke care in 2 English cities, and what kinds of effects involvement was thought to produce.
Methods
Analysis of documents from both MSC projects, and retrospective in‐depth interviews with 45 purposively selected individuals (providers, commissioners, third‐sector employees) involved in the MSC.
Results
Involvement was enacted through consultation exercises; lay membership of governance structures; and elicitation of patient perspectives. Interviewees’ views of involvement in these MSCs varied, reflecting different views of involvement per se, and of implicit quality criteria. The value of involvement lay not in its contribution to acute service redesign but in its facilitation of the changes developed by professionals. We propose 3 conceptual categories—agitation management, verification and substantiation—to identify types of process through which involvement was seen to facilitate system change.
Discussion
Involvement was seen to have strategic and intrinsic value. Its strategic value lay in facilitating the implementation of a model of care that aimed to deliver evidence‐based care to all; its intrinsic value was in the idea of citizen participation in change processes as an end in its own right. The concept of value, rather than impact, may provide greater traction in analyses of contemporary involvement practices.
Rapid advances in eradicating invasive species from islands are improving conservation outcomes in these biodiversity hotspots. However, recent conservation gains could be reversed not only by future ...invasions from non-native species but also by future extinctions of native taxa, both of which may be facilitated by – or exacerbated by interactions among drivers of – global environmental change. We highlight relevant knowledge gaps that must be filled to reduce uncertainty about the ecological effects of future climate change. We use Aotearoa New Zealand as a case study of island ecosystems to demonstrate that in addition to sealevel rise, most ecologically meaningful impacts of climate change on biodiversity responses are indirect and due to exacerbation of existing threats, including the impact of invasive species as well as the loss and fragmentation of habitat. We identify key topics where progress is needed to future-proof conservation management for island ecosystems susceptible to the direct and indirect effects of climate change.
The centralisation of specialist cancer surgical services across London Cancer and Greater Manchester Cancer, England, may significantly change how patients experience care. These centres are ...changing specialist surgical pathways for several cancers including prostate, bladder, kidney, and oesophago-gastric cancers, increasing the specialisation of centres and providing surgery in fewer hospitals. While there are potential benefits related to centralising services, changes of this kind are often controversial. The aim of this study was to identify factors related to the centralisation of specialist surgical services that are important to patients, carers and health care professionals.
This was a questionnaire-based study involving a convenience sample of patient and public involvement (PPI) and cancer health care professional (HCP) sub-groups in London and Greater Manchester (n = 186). Participants were asked to identify which of a list of factors potentially influenced by the centralisation of specialist cancer surgery were important to them and to rank these in order of importance. We ranked and shortlisted the most important factors.
We obtained 52 responses (28% response rate). The factors across both groups rated most important were: highly trained staff; likelihood and severity of complications; waiting time for cancer surgery; and access to staff members from various disciplines with specialised skills in cancer. These factors were also ranked as being important separately by the PPI and HCP sub-groups. There was considerable heterogeneity in the relative ordering of factors within sub-groups and overall.
This study examines and ranks factors important to patients and carers, and health care professionals in order to inform the implementation of centralisation of specialist cancer surgical services. The most important factors were similar in the two stakeholder sub-groups. Planners should consider the impact of reorganising services on these factors, and disseminate this information to patients, the public and health care professionals when deciding whether or not and how to centralise specialist cancer surgical services.
Purpose
Quantitative MRI (qMRI) was performed using a 1.5T protocol that includes a novel chemical exchange saturation transfer/magnetization transfer (CEST/MT) approach. The purpose of this ...prospective study was to determine if qMRI metrics at baseline, at the 10th and 20th fraction during a 30 fraction/6 week standard chemoradiation (CRT) schedule, and at 1 month following treatment could be an early indicator of response for glioblastoma (GBM).
Methods
The study included 51 newly diagnosed GBM patients. Four regions-of-interest (ROI) were analyzed: (i) the radiation defined clinical target volume (CTV), (ii) radiation defined gross tumor volume (GTV), (iii) enhancing-tumor regions, and (iv) FLAIR-hyperintense regions. Quantitative CEST, MT, T
1
and T
2
parameters were compared between those patients progressing within 6.9 months (early), and those progressing after CRT (late), using mixed modelling. Exploratory predictive modelling was performed to identify significant predictors of early progression using a multivariable LASSO model.
Results
Results were dependent on the specific tumor ROI analyzed and the imaging time point. The baseline CEST asymmetry within the CTV was significantly higher in the early progression cohort. Other significant predictors included the T
2
of the MT pools (for semi-solid at fraction 20 and water at 1 month after CRT), the exchange rate (at fraction 20) and the MGMT methylation status.
Conclusions
We observe the potential for multiparametric qMRI, including a novel pulsed CEST/MT approach, to show potential in distinguishing early from late progression GBM cohorts. Ultimately, the goal is to personalize therapeutic decisions and treatment adaptation based on non-invasive imaging-based biomarkers.
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