Part 1. Are the legal grounds underlying Supreme Court decisions strategically chosen? This paper makes three improvements to previous efforts to answer this question. One, I disaggregate the data by ...issue type, justice ideology, and time. Two, I investigate not just the effects of external political constraint on instrument choice, but also the effects of consistency between the direction of case outcome and justice ideology. Three, I use the Bailey (2007) ideology scores, which offer better scaling of Court and Congress estimates. I find that, between 1953 and 2002, external constraint is almost never associated with higher probability of constitutional instrument use, but that ideological consistency often is, especially for liberals deciding civil liberties cases. Part 2. At what stage of the review process does the Supreme Court make its instrument choice - when disposing of a case on its merits, or when setting the Court agenda? Most of the cases heard by the Supreme Court 1953-2002 concern either constitutional or statutory provisions, not both, and thus offer only one instrument option. This suggests that agenda-setting is the main venue of strategic instrument choice. An analysis of Rehnquist Court cases finds that those predicted to have outcomes in line with justice ideological preferences contain a larger percentage of cases concerning constitutional provisions, even after controlling for issue area and cert rationale. This supports the idea that justices are more likely to grant certiorari to constitutional cases projected to have preferred outcomes. Part 3. The Supreme Court claimed supervisory authority over lower federal court procedure, a powerful legal instrument that allows the pursuit of policies beyond constitutional standards. Supervisory power is a neglected subject in political science, and this paper examines its strategic potential and the way it is used by the Court. Analyzing criminal procedure cases 1953-2002, I find that supervisory power is mainly used by liberal justices making pro-defendant decisions, and that liberals are likely to use the more durable constitutional instrument instead of supervisory power when facing an ideologically distant Congress.
In adults, human mesenchymal stem cells (hMSCs) are found in vivo at low frequency and are defined by their capacity to differentiate into bone, cartilage, and adipose tissue, depending on the ...stimuli and culture conditions under which they are expanded. Although MSCs were initially hypothesized to be the panacea for regenerating tissues, MSCs appear to be more important in therapeutics to regulate the immune response invoked in settings such as tissue injury, transplantation, and autoimmunity. MSCs have been used therapeutically in clinical trials and subsequently in practice to treat graft-versus-host disease following bone marrow transplantation. Reports of successful immune modulation suggest efficacy in a wide range of autoimmune conditions, such as demyelinating neurological disease (multiple sclerosis), systemic lupus erythematosus, and Crohn's disease, among others. This review provides background information about hMSCs and also describes their putative mechanisms of action in inflammation. We provide a summary of ongoing clinical trials to allow (a) full comprehension of the range of diseases in which hMSC therapy may be beneficial and (b) identification of gaps in our knowledge about the mechanisms of action of therapeutic MSCs in disease.
Tilapia are an important global food source due to their omnivorous diet, tolerance for high-density aquaculture, and relative disease resistance. Since 2009, tilapia aquaculture has been threatened ...by mass die-offs in farmed fish in Israel and Ecuador. Here we report evidence implicating a novel orthomyxo-like virus in these outbreaks. The tilapia lake virus (TiLV) has a 10-segment, negative-sense RNA genome. The largest segment, segment 1, contains an open reading frame with weak sequence homology to the influenza C virus PB1 subunit. The other nine segments showed no homology to other viruses but have conserved, complementary sequences at their 5' and 3' termini, consistent with the genome organization found in other orthomyxoviruses. In situ hybridization indicates TiLV replication and transcription at sites of pathology in the liver and central nervous system of tilapia with disease.
The economic impact of worldwide trade in tilapia is estimated at $7.5 billion U.S. dollars (USD) annually. The infectious agent implicated in mass tilapia die-offs in two continents poses a threat to the global tilapia industry, which not only provides inexpensive dietary protein but also is a major employer in the developing world. Here we report characterization of the causative agent as a novel orthomyxo-like virus, tilapia lake virus (TiLV). We also describe complete genomic and protein sequences that will facilitate TiLV detection and containment and enable vaccine development.
Salivary duct carcinoma (SDC) is a rare, aggressive malignancy with limited treatment options and poor outcome. Twenty-nine primary resected SDC, including 15 SDC de novo (SDCDN), and 14 SDC ex ...pleomorphic adenoma (SDCXPA) were subjected to the massive parallel sequencing assay (MSK-IMPACT) targeting 287 to 468 cancer-related genes. TP53 was the most frequently altered gene (69%). TP53 mutations and ERBB2 amplification were more frequent in SDCXPA than in SDCDN (P = .0007 and P = .01, respectively). Potentially targetable mutations were detected in 79% (23/29) of SDC involving ERBB2 (31%), PIK3CA (28%), HRAS (21%), ALK (7%) and BRAF (3%), and 22% (5/23) of those cases harbored possible primary resistance mutations involving CCNE1, NF1 and PTEN. A novel HNRNPH3-ALK rearrangement was found in one SDCDN. In another case, EML4-ALK fusion detected in the primary tumor was associated with ALK G1202R secondary resistance mutation in the post-treatment metastasis. A germline analysis of the DNA repair genes revealed a case with a pathogenic BRCA1 E23fs germline variant. SDCDN and SDCXPA are genetically distinct. Although the majority of SDC may be amenable to molecular targeted therapy, concurrent possible resistance mutations may be found in a significant minority of cases. A broad genomic profiling is necessary to ensure detection of rare but clinically actionable somatic alterations in SDC.
•79% SDC harbor targetable somatic mutations.•22% SDC with targetable somatic mutations may harbor concurrent primary resistance mutations.•A novel HNRNPH3-ALK rearrangement is detected in SDC.•ALK inhibition in an EML4-ALK positive SDC can lead to ALK G1202R secondary resistance mutation.•First SDC patient harboring BRCA1 E23fs germline mutation is reported.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over‐expression of Lin28a have shown related phenotypes. Here, we ...describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b‐deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue‐specific KO mice implicated skeletal muscle‐deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo‐insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life‐long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. STEM Cells 2013;31:1563–1573
(1) Objective: The World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) classification is a unified framework for the description of health and ...health-related states. This study aimed to use the ICF framework to classify outcome measures used in follow-up studies of coronavirus outbreaks and make recommendations for future studies. (2) Methods: EMBASE, MEDLINE, CINAHL and PsycINFO were systematically searched for original studies assessing clinical outcomes in adult survivors of severe acute respiratory distress syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease-19 (COVID-19) after hospital discharge. Individual items of the identified outcome measures were linked to ICF second-level and third-level categories using ICF linking rules and categorized according to an ICF component. (3) Results: In total, 33 outcome measures were identified from 36 studies. Commonly used (a) ICF body function measures were Pulmonary Function Tests (PFT), Impact of event scale (IES-R) and Hospital Anxiety and Depression Scale (HADS); (b) ICF activity was 6-Minute Walking Distance (6MWD); (c) ICF participation measures included Short Form-36 (SF-36) and St George's Respiratory Questionnaire (SGRQ). ICF environmental factors and personal factors were rarely measured. (4) Conclusions: We recommend future COVID-19 follow-up studies to use the ICF framework to select a combination of outcome measures that capture all the components for a better understanding of the impact on survivors and planning interventions to maximize functional return.
OBJECTIVE—High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between ...HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function.
APPROACH AND RESULTS—Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX.
CONCLUSIONS—WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT00163943
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