The Emperor\u27s New Clothes: A Survey of Significant Court Decisions Interpreting Pennsylvania\u27s Sovereign Immunity Act and Its Waivers

This article surveys and analyzes the history of sovereign immunity in the Commonwealth of Pennsylvania. The article traces the adoption of sovereign immunity, its abrogation by the Pennsylvania Supreme Court, and the General Assembly\u27s reaffirmation of the doctrine in the Sovereign Immunity Act. The article provides a review of the important sections of the Sovereign Immunity Act and examines many of the appellate decisions which have addressed the Act and the waivers of immunity contained therein

Seasonal and ontogenetic variation in depth use by a critically endangered benthic elasmobranch and its implications for spatial management

The project was undertaken through the Movement Ecology of the Flapper skate project at St Andrews and received support from the Ecology and Conservation Group, Marine Scotland Science, and Marine Scotland Planning & Policy and NatureScot. It was funded by Marine Scotland projects SP004 and SP02B0 and NatureScot project 015960.Seasonal and ontogenetic variation in depth use by benthic species are often concomitant with changes in their spatial distribution. This has implications for the efficacy of spatial conservation measures such as Marine Protected Areas (MPAs). The critically endangered flapper skate (Dipturus intermedius) is the designation feature of an MPA in Scotland. This species is generally associated with deeper waters >100 m; however, little is known about its seasonal or ontogenetic variation in habitat use. This study used archival depth data from 25 immature and mature flapper skate tagged in the MPA over multiple years. Time series ranged from 3 to 772 (mean = 246) days. Generalised additive mixed models and highest density intervals were used to identify home (95%) and core (50%) highest density depth regions (HDDRs) to quantify depth use in relation to time of year and body size. Skate used a total depth range of 1 – 312 m, but home HDDRs typically occurred between 20 – 225 m. Core HDDRs displayed significant seasonal and ontogenetic variation. Summer core HDDRs (100 – 150 m) suggest high occupancy of the deep trenches in the region by skate of most size classes. There was an inverse relationship between body size and depth use, and a seasonal trend of skate moving into shallow water over winter months. These results suggest flapper skate are not solely associated with deep water, as skate, especially large females, are frequently found in shallow waters (25 – 75 m). The current management, which protects the entire depth range, is appropriate for the protection of flapper skate through much of its life-history. This research demonstrates why collecting data across seasonal scales and multiple ontogenetic stages is needed to assess the effectiveness of spatial management.Publisher PDFPeer reviewe

Environmental cycles and individual variation in the vertical movements of a benthic elasmobranch

This research was supported by a PhD Studentship at the University of St Andrews, jointly funded by NatureScot via the Marine Alliance for Science and Technology for Scotland (MASTS), and the Centre for Research into Ecological and Environmental Modelling. The data were collected as part of research funded by NatureScot (project 015960) and Marine Scotland (projects SP004 and SP02B0) and the Movement Ecology of Flapper Skate (MEFS) project funded by the same organisations. Additional funding was provided from MASTS, in the form of a Small Research Grant, and Shark Guardian. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.Trends in depth and vertical activity reflect the behaviour, habitat use and habitat preferences of marine organisms. However, among elasmobranchs, research has focused heavily on pelagic sharks, while the vertical movements of benthic elasmobranchs, such as skate (Rajidae), remain understudied. In this study, the vertical movements of the Critically Endangered flapper skate (Dipturus intermedius) were investigated using archival depth data collected at 2 min intervals from 21 individuals off the west coast of Scotland (56.5°N, −5.5°W) in 2016–17. Depth records comprised nearly four million observations and included eight time series longer than 1 year, forming one of the most comprehensive datasets collected on the movement of any skate to date. Additive modelling and functional data analysis were used to investigate vertical movements in relation to environmental cycles and individual characteristics. Vertical movements were dominated by individual variation but included prolonged periods of limited activity and more extensive movements that were associated with tidal, diel, lunar and seasonal cycles. Diel patterns were strongest, with irregular but frequent movements into shallower water at night, especially in autumn and winter. This research strengthens the evidence for vertical movements in relation to environmental cycles in benthic species and demonstrates a widely applicable flexible regression framework for movement research that recognises the importance of both individual-specific and group-level variation.Publisher PDFPeer reviewe

Assessment of processes and operating conditions in UK pork abattoirs

In order to determine typical and atypical operations in the slaughtering and dressing of pigs for pork and bacon practices and operations were recorded at eight pig abattoirs. Data included physical parameters such as temperatures and durations. The results indicate that plants are reasonably similar if processing pigs mainly for pork, but those processing mainly for bacon had more aggressive singeing and polishing (black scraper) arrangements. The plants visited used either hot water (tank) or vertical (sprayed hot water) scalding systems prior to dehairing

Infundibular sparing versus transinfundibular approach to the repair of tetralogy of Fallot

IntroductionThe right ventricular infundibular sparing approach (RVIS) to the repair of tetralogy of Fallot (TOF) avoids a full‐thickness ventricular incision, typically utilized in the transinfundibular (TI) method.MethodsWe performed a retrospective, age‐matched cohort study of patients who underwent RVIS at Texas Children’s Hospital or TI at Children’s Hospital Medical Center in Nebraska and subsequently underwent cardiac magnetic resonance imaging (CMR). We compared right ventricular end‐diastolic and systolic volumes indexed to body surface area (RVEDVi and RVESVi) and right ventricular ejection fraction (RVEF) as primary endpoints. Secondary endpoints were indexed left ventricular diastolic and systolic volume (LVEDVi and LVESVi), left ventricular ejection fraction (LVEF), right ventricular (RV) sinus ejection fraction (EF) and RV outflow tract EF (RVOT EF).ResultsSeventy‐nine patients were included in the analysis; 40 underwent RVIS and 39 underwent TI repair. None of the patients in the TI repair group had an initial palliation with a systemic to pulmonary arterial shunt compared to seven (18%) in the RVIS group (P < .01). There was no appreciable difference in RVEDVi (122 ± 29 cc/m2 vs 130 ± 29 cc/m2, P = .59) or pulmonary regurgitant fraction (40 ± 13 vs 37 ± 18, P = .29) between the RVIS and TI groups. Compared to the TI group, the RVIS group had higher RVEF (54 ± 6% vs 44 ± 9%, P < .01), lower RVESV (57 ± 17 cc/m2 vs 67 ± 25 cc/m2, P = .03), higher LVEF (61 ± 11% vs 54 ± 8%, P < .01), higher RVOT EF (47 ± 12% vs 41 ± 11%, P = .03), and higher RV sinus EF (56 ± 5% vs 49 ± 6%, P < .01)ConclusionsIn this selected cohort, patients who underwent RVIS repair for TOF had higher right and left ventricular ejection fraction compared to those who underwent TI repair.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152818/1/chd12863_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152818/2/chd12863.pd

Statistical methods for non-adherence in non-inferiority trials: useful and used? A systematic review.

BACKGROUND: In non-inferiority trials with non-adherence to interventions (or non-compliance), intention-to-treat and per-protocol analyses are often performed; however, non-random non-adherence generally biases these estimates of efficacy. OBJECTIVE: To identify statistical methods that adjust for the impact of non-adherence and thus estimate the causal effects of experimental interventions in non-inferiority trials. DESIGN: A systematic review was conducted by searching the Ovid MEDLINE database (31 December 2020) to identify (1) randomised trials with a primary analysis for non-inferiority that applied (or planned to apply) statistical methods to account for the impact of non-adherence to interventions, and (2) methodology papers that described such statistical methods and included a non-inferiority trial application. OUTCOMES: The statistical methods identified, their impacts on non-inferiority conclusions, and their advantages/disadvantages. RESULTS: A total of 24 papers were included (4 protocols, 13 results papers and 7 methodology papers) reporting relevant methods on 26 occasions. The most common were instrumental variable approaches (n=9), including observed adherence as a covariate within a regression model (n=3), and modelling adherence as a time-varying covariate in a time-to-event analysis (n=3). Other methods included rank preserving structural failure time models and inverse-probability-of-treatment weighting. The methods identified in protocols and results papers were more commonly specified as sensitivity analyses (n=13) than primary analyses (n=3). Twelve results papers included an alternative analysis of the same outcome; conclusions regarding non-inferiority were in agreement on six occasions and could not be compared on six occasions (different measures of effect or results not provided in full). CONCLUSIONS: Available statistical methods which attempt to account for the impact of non-adherence to interventions were used infrequently. Therefore, firm inferences about their influence on non-inferiority conclusions could not be drawn. Since intention-to-treat and per-protocol analyses do not guarantee unbiased conclusions regarding non-inferiority, the methods identified should be considered for use in sensitivity analyses. PROSPERO REGISTRATION NUMBER: CRD42020177458

On the breaking of a plasma wave in a thermal plasma: I. The structure of the density singularity

The structure of the singularity that is formed in a relativistically large amplitude plasma wave close to the wavebreaking limit is found by using a simple waterbag electron distribution function. The electron density distribution in the breaking wave has a typical "peakon" form. The maximum value of the electric field in a thermal breaking plasma is obtained and compared to the cold plasma limit. The results of computer simulations for different initial electron distribution functions are in agreement with the theoretical conclusions.Comment: 21 pages, 12 figure

Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1α Stability in Aerobic Conditions.

Hypoxia-inducible transcription factors (HIFs) control adaptation to low oxygen environments by activating genes involved in metabolism, angiogenesis, and redox homeostasis. The finding that HIFs are also regulated by small molecule metabolites highlights the need to understand the complexity of their cellular regulation. Here we use a forward genetic screen in near-haploid human cells to identify genes that stabilize HIFs under aerobic conditions. We identify two mitochondrial genes, oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1α in a non-hydroxylated form. Disruption of OGDH complex activity in OGDH or LIAS mutants promotes L-2-hydroxyglutarate formation, which inhibits the activity of the HIFα prolyl hydroxylases (PHDs) and TET 2-oxoglutarate dependent dioxygenases. We also find that PHD activity is decreased in patients with homozygous germline mutations in lipoic acid synthesis, leading to HIF1 activation. Thus, mutations affecting OGDHC activity may have broad implications for epigenetic regulation and tumorigenesis.This work was supported by a Wellcome Trust Senior Clinical Research Fellowship to J.A.N. (102770/Z/13/Z), Wellcome Trust Principal Research Fellowship to P.J.L. (084957/Z/08/Z), and the Medical Research Council (A.S.H.C. and C.F.). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140).This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cmet.2016.09.01

Adolescent tuberculosis.

Adolescence is characterised by a substantial increase in the incidence of tuberculosis, a known fact since the early 20th century. Most of the world's adolescents live in low-income and middle-income countries where tuberculosis remains common, and where they comprise a quarter of the population. Despite this, adolescents have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services, and emerging evidence suggests that current models of care do not meet their needs. This Review discusses up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. We outline the progress in vaccine development and highlight important directions for future research