Clear Cell Cancer of the Uterine Corpus: The Association of Clinicopathologic Parameters and Treatment on Disease Progression

This paper presents a single-institution experience regarding the clinicopathologic features and treatment strategies used in uterine clear cell cancer (UCC), a rare, aggressive histologic subtype of uterine cancer with poor prognosis and discusses parameters associated with progression-free survival (PFS) and overall survival (OS). A retrospective chart review was performed on all patients (n = 80) diagnosed with UCC and treated between 1994 and 2009 at a single academic institution. Data on demographics, FIGO stage, treatment regimens, and recurrences were collected. Patients with early-stage UCC had an excellent survival regardless of adjuvant therapy. Advanced-stage patients had a worse survival. Vaginal apex brachytherapy was associated with an increased OS (P = 0.02) but not PFS (P = 0.10). The use of platinum-based chemotherapy in combination with vaginal apex brachytherapy did not significantly improve survival. Innovative therapies still need to be identified for this uncommon uterine cancer

Gaucher disease: A cause of massive splenomegaly in a 15-year-old black African male

Patients with Gaucher disease (GD), a rare autosomal recessive lysosomal storage disease, commonly present to paediatricians with massive splenomegaly. While the diagnosis and management of patients with this chronic multisystem disorder has evolved significantly in recent years, the initial diagnosis represents a challenge. We describe the case of a 15-year-old black African male who presented with abdominal distension, delayed growth and fatigue. Initial laboratory studies revealed severe anaemia (haemoglobin concentration 8 g/dL) and moderate thrombocytopenia (platelet count 80 × 109/L). A computed tomography scan of the abdomen showed an enlarged liver of 173 mm and massive splenomegaly of 27 mm. The diagnosis of GD was confirmed by reduced beta-glucocerebrosidase activity and heterozygous mutations in the GBA1 gene. The patient was managed at a dedicated paediatric haematology unit with enzyme replacement therapy and regular clinical, biochemical and radiological monitoring

In the Absence of Frazzled Over-Expression of Abelson Tyrosine Kinase Disrupts Commissure Formation and Causes Axons to Leave the Embryonic CNS

BACKGROUND: In the Drosophila embryonic nerve cord, the formation of commissures require both the chemoattractive Netrin receptor Frazzled (Fra) and the Abelson (Abl) cytoplasmic tyrosine kinase. Abl binds to the cytoplasmic domain of Fra and loss-of-function mutations in abl enhance fra-dependent commissural defects. To further test Abl's role in attractive signaling, we over-expressed Abl in Fra mutants anticipating rescue of commissures. METHODOLOGY/PRINCIPAL FINDINGS: The Gal4-UAS system was used to pan-neurally over-express Abl in homozygous fra embryos. Surprisingly, this led to a significant decrease in both posterior and anterior commissure formation and induced some commissural and longitudinal axons to project beyond the CNS/PNS border. Re-expressing wild-type Fra, or Fra mutants with a P-motif deleted, revert both commissural and exiting phenotypes, indicating that Fra is required but not a specific P-motif. This is supported by S2 cell experiments demonstrating that Abl binds to Fra independent of any specific P-motif and that Fra continues to be phosphorylated when individual P-motifs are removed. Decreasing midline repulsion by reducing Robo signaling had no effect on the Abl phenotype and the phenotypes still occur in a Netrin mutant. Pan-neural over-expression of activated Rac or Cdc42 in a fra mutant also induced a significant loss in commissures, but axons did not exit the CNS. CONCLUSION/SIGNIFICANCE: Taken together, these data suggest that Fra activity is required to correctly regulate Abl-dependent cytoskeletal dynamics underlying commissure formation. In the absence of Fra, increased Abl activity appears to be incorrectly utilized downstream of other guidance receptors resulting in a loss of commissures and the abnormal projections of some axons beyond the CNS/PNS border

Exploring the Potential of Miniature Electrodynamic Tethers and Developments in the Miniature Tether Electrodynamics Experiment

The success of nanospacecraft has spurred an interest in using even smaller satellites for longer-duration, constellation scale missions, requiring the use of a propulsion source on board to counteract the effects of drag and for coordination and maneuverability. Previous papers have shown that the use of short electrodynamic tethers (EDTs) has the potential to provide propellentless propulsion for drag make-up and the ability to change orbits of these small satellites. The Miniature Tether Electrodynamics Experiment (MiTEE) mission is a student-led technology demonstration mission by the University of Michigan to demonstrate the use of these short EDTs in a 1U CubeSat frame. This paper presents updates for the major MiTEE subsystems. The mission has progressed significantly with the use of a high-altitude balloon flight successfully demonstrating the communications subsystem and satellite integration. The paper concludes with an overview of the future plans for the MiTEE mission

Prevalence of self-reported disability, activity limitation and social participation in Sri Lanka

Introduction The World Health Organization estimates that 15% of the global population has a disability. Available evidence from Sri Lanka shows variable estimates of the magnitude of disability. Objectives Determine the prevalence of self-reported disability in the adult population aged ≥18 years, and associated risk factors in a nationally representative sample in Sri Lanka. Methods The Washington Group short questionnaire was used to identify persons with self-reported disability. Data were collected from responsible adults aged ≥18 years in the selected households. A four point-scale: “no difficulty”, “some difficulty”, “a lot of difficulty” and “cannot do at all” was used. Individuals screening positive for disability were administered an additional questionnaire on activity limitations, social participation and their health and financial concerns. Results Overall 41.5% (4131) [95% CI: 40.5-42.4] reported functional difficulty in at least one domain. The prevalence of disability, i.e. a lot of difficulty or cannot do at all was 3.8% (382) [95% CI: 3.5 – 4.2], while the prevalence of “some functional difficulty” was 37.6% (3749) [95% CI: 36.7-38.6]. The prevalence of disability increased with age and was higher among females, urban residents, and those with lower education and socio-economic status. Minor degrees of functional difficulties were more common among older people, females and people with lower education. Conclusions The prevalence of disability and varying degrees of functional difficulty is high among the adult population of Sri Lanka. Evidence shows that a strategic plan is required to address the magnitude of disability and functional limitations in Sri Lanka

Results from the Supernova Photometric Classification Challenge

We report results from the Supernova Photometric Classification Challenge (SNPCC), a publicly released mix of simulated supernovae (SNe), with types (Ia, Ibc, and II) selected in proportion to their expected rate. The simulation was realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point-spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). A spectroscopically confirmed subset was provided for training. We challenged scientists to run their classification algorithms and report a type and photo-z for each SN. Participants from 10 groups contributed 13 entries for the sample that included a host-galaxy photo-z for each SN, and 9 entries for the sample that had no redshift information. Several different classification strategies resulted in similar performance, and for all entries the performance was significantly better for the training subset than for the unconfirmed sample. For the spectroscopically unconfirmed subset, the entry with the highest average figure of merit for classifying SNe~Ia has an efficiency of 0.96 and an SN~Ia purity of 0.79. As a public resource for the future development of photometric SN classification and photo-z estimators, we have released updated simulations with improvements based on our experience from the SNPCC, added samples corresponding to the Large Synoptic Survey Telescope (LSST) and the SDSS, and provided the answer keys so that developers can evaluate their own analysis.Comment: accepted by PAS

Rational design and characterization of bioplastics from Hermetia illucens prepupae proteins

In this study proteins extracted from prepupae of Hermetia illucens, also known as black soldier fly,are investigated as promising base for a new type of bioplastics for agricultural purposes. Designof experiments techniques are employed to perform a rational study on the effects of differentcombination of glycerol as plasticizer, citric acid as cross-linking agent and distilled water as solventon the capability of proteins to form a free-standing film through casting technique, keeping asfixed the quantity of proteins. Glycerol shows interesting properties as plasticizer contributing tothe formation of homogenous and free-standing film. Moreover, mechanical and thermalcharacterizations are performed to estimate the effect of increasing amounts of proteins on thefinal properties and thickness of the specimens. Proteins derived from H. illucens can be success-fully employed as base for bioplastics to be employed for agricultural purposes

What does it mean to be affiliated with care?: Delphi consensus on the definition of unaffiliation and specialist in sickle cell disease

Accruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a SCD expert provider . In this study, we conducted a Delphi process to obtain expert consensus on what it means to be an unaffiliated patient with SCD and to define an SCD specialist, as no standard definition is available. Twenty-eight SCD experts participated in three rounds of questions. Consensus was defined as 80% or more of respondents agreeing. Experts reached consensus that an individual with SCD who is unaffiliated from care is someone who has not been seen by a sickle cell specialist in at least a year. A sickle cell specialist was defined as someone with knowledge and experience in SCD. Having knowledge means: being knowledgeable of the 2014 NIH Guidelines, Evidence-Based Management of SCD , trained in hydroxyurea management and transfusions, trained on screening for organ damage in SCD, trained in pain management and on SCD emergencies, and is aware of psychosocial and cognitive issues in SCD. Experiences that are expected of a SCD specialist include experience working with SCD patients, mentored by a SCD specialist, regular attendance at SCD conferences, and obtains continuing medical education on SCD every 2 years. The results have strong implications for future research, practice, and policy related to SCD by helping to lay a foundation for an new area of research (e.g., to identify subpopulations of unaffiliation and targeted interventions) and policies that support reaffiliation and increase accessibility to quality care

Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: Implications for AMP Kinase

Mammalian cytochrome c (Cytc) plays a key role in cellular life and death decisions, functioning as an electron carrier in the electron transport chain and as a trigger of apoptosis when released from the mitochondria. However, its regulation is not well understood. We show that the major fraction of Cytc iso- lated from kidneys is phosphorylated on Thr28, leading to a par- tial inhibition of respiration in the reaction with cytochrome c oxidase. To further study the effect of Cytc phosphorylation in vitro, we generated T28E phosphomimetic Cytc, revealing supe- rior behavior regarding protein stability and its ability to degrade reactive oxygen species compared with wild-type un- phosphorylated Cytc. Introduction of T28E phosphomimetic Cytc into Cytc knock-out cells shows that intact cell respiration, mitochondrial membrane potential (����m), and ROS levels are reduced compared with wild type. As we show by high resolu- tion crystallography of wild-type and T28E Cytc in combination with molecular dynamics simulations, Thr28 is located at a cen- tral position near the heme crevice, the most flexible epitope of the protein apart from the N and C termini. Finally, in silico prediction and our experimental data suggest that AMP kinase, which phosphorylates Cytc on Thr28 in vitro and colocalizes with Cytc to the mitochondrial intermembrane space in the kid- ney, is the most likely candidate to phosphorylate Thr28 in vivo. We conclude that Cytc phosphorylation is mediated in a tissue- specific manner and leads to regulation of electron transport chain flux via “controlled respiration,” preventing ����m hyperpolarization, a known cause of ROS and trigger of apoptosis