Morphology of the inner and peripheral ear of the loricariid catfish Pterygoplichthys gibbiceps K.

The morphology of the peripheral and inner ear structures was studied in the loricariid catfish Pterygoplichthys gibbiceps. Specimens (n=6) were preserved in fixative (4% paraformaldehyde, 2% glutaraldehyde in 0.1M phosphate buffer) and dissected for examination of the gross morphology (using light microscopy) and ultrastructure of the auditory sensory epithelia (using scanning electron microscopy). One additional specimen was cleaned in a dermestid beetle colony in order to examine the osteology of the skull. The swim bladder of P. gibbiceps is divided along the midline of the fish into two reduced but equal lobes residing in two laterally oriented bony encapsulations. Immediately lateral to the swim bladders, fenestrations were observed in the pterotic + supracleithrum. A single Weberian ossicle was attached to the medial apex of the bladder, which translates external sound pressure energy into interaural hydrodynamic motion of the fluid within the pars inferior. The single ossicle bends 90o through a bone which acts as a pivot point allowing linear motion at the extreme ends of the ossicle. Otoliths (solid calcareous bones in the inner ear) were similar in shape to those of other loricariids. The asteriscus was disk-like and had a large crescent shaped sulcus that covered the macular striola. Sagittae were slender at their caudal apex and exhibited two wing-like projections about the rostral region of the otolith. Utricular otoliths were thick, having a bulbous rostral region and a laterally flattened triangular caudal region. On its ventral surface there was a deep sigma-shaped sulcus which was not in contact with the utricular maculae. Auditory endorgan-specific patterns of the orientation of sensory hair cell kinocilia were observed on each macular surface. Maculae exhibited areas of reversed hair cell orientation called the striola. Sacculi possessed a vertical striolar pattern. The lagenar patterns were crescent shaped in similar fashion as the sulcus of the otolith, and the pattern of the utricle was unlike the shape its otolith and curved sigmoidally to terminate at the lateral extremities of the otolith. In general, while there are unique peripheral auditory structures in P. gibbiceps (bi-lobed and encapsulated swim bladders and a single Weberian ossicle), the inner ear maculae and striolar patterns found in P. gibbiceps are similar to those found in other catfishes

Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading

The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (approx. 9 inches from the source) dominated by direct wave propagation, mid-field environment (approx. 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This report documents the outcome of the assessment

Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading: Appendices

The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (approx. 9 inches from the source) dominated by direct wave propagation, mid-field environment (approx. 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This document contains appendices to the Volume I report

Prospectus, April 13, 2011

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Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading

The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (~9 inches from the source) dominated by direct wave propagation, mid-field environment (approximately 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This document contains appendices to the Volume I report

Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): a randomised, open-label phase 2/3 trial

BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m(2) by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40–50 mg/m(2) by body surface area once every 4 weeks; intravenous topotecan 4 mg/m(2) by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9–15·0) compared with 7·2 months (5·6–9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36–0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis

A patient safety toolkit for family practices

Objectives: Major gaps remain in our understanding of primary care patient safety. We describe a toolkit for measuring patient safety in family practices. Methods: Six tools were used in 46 practices. These tools were: NHS Education for Scotland Trigger Tool, NHS Education for Scotland Medicines Reconciliation Tool, Primary Care Safequest, Prescribing Safety Indicators, PREOS-PC, and Concise Safe Systems Checklist. Results: PC-Safequest showed that most practices had a well-developed safety climate. However, the Trigger Tool revealed that a quarter of events identified were associated with moderate or substantial harm, with a third originating in primary care and avoidable. Although medicines reconciliation was undertaken within 2 days in >70% of cases, necessary discussions with a patient/carer did not always occur. The prescribing safety indicators identified 1,435 instances of potentially hazardous prescribing or lack of recommended monitoring (from 92,649 patients). The Concise Safe Systems Checklist found that 25% of staff thought their practice provided inadequate follow-up for vulnerable patients discharged from hospital and inadequate monitoring of non-collection of prescriptions. Most patients had a positive perception of the safety of their practice although 45% identified at least one safety problem in the past year. Conclusions: Patient safety is complex and multidimensional. The Patient Safety Toolkit is easy to use and hosted on a single platform with a collection of tools generating practical and actionable information. It enables family practices to identify safety deficits that they can review and change procedures to improve their patient safety across a key sets of patient safety issues

B 12 -Mediated, Long Wavelength Photopolymerization of Hydrogels

Medical hydrogel applications have expanded rapidly over the past decade. Implantation in patients by non-invasive injection is preferred, but this requires hydrogel solidification from a low viscosity solution to occur in vivo via an applied stimuli. Transdermal photo-crosslinking of acrylated biopolymers with photoinitiators and lights offers a mild, spatiotemporally controlled solidification trigger. However, the current short wavelength initiators limit curing depth and efficacy because they do not absorb within the optical window of tissue (600 - 900 nm). As a solution to the current wavelength limitations, we report the development of a red light responsive initiator capable of polymerizing a range of acrylated monomers. Photo-activation occurs within a range of skin type models containing high biochromophore concentrations

Extraocular, rod-like photoreceptors in a flatworm express xenopsin photopigment.

Animals detect light using opsin photopigments. Xenopsin, a recently classified subtype of opsin, challenges our views on opsin and photoreceptor evolution. Originally thought to belong to the Gαi-coupled ciliary opsins, xenopsins are now understood to have diverged from ciliary opsins in pre-bilaterian times, but little is known about the cells that deploy these proteins, or if they form a photopigment and drive phototransduction. We characterized xenopsin in a flatworm, Maritigrella crozieri, and found it expressed in ciliary cells of eyes in the larva, and in extraocular cells around the brain in the adult. These extraocular cells house hundreds of cilia in an intra-cellular vacuole (phaosome). Functional assays in human cells show Maritigrella xenopsin drives phototransduction primarily by coupling to Gαi. These findings highlight similarities between xenopsin and c-opsin and reveal a novel type of opsin-expressing cell that, like jawed vertebrate rods, encloses the ciliary membrane within their own plasma membrane

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy