An Activity-Based Nanosensor for Traumatic Brain Injury.

Currently, traumatic brain injury (TBI) is detected by medical imaging; however, medical imaging requires expensive capital equipment, is time- and resource-intensive, and is poor at predicting patient prognosis. To date, direct measurement of elevated protease activity has yet to be utilized to detect TBI. In this work, we engineered an activity-based nanosensor for TBI (TBI-ABN) that responds to increased protease activity initiated after brain injury. We establish that a calcium-sensitive protease, calpain-1, is active in the injured brain hours within injury. We then optimize the molecular weight of a nanoscale polymeric carrier to infiltrate into the injured brain tissue with minimal renal filtration. A calpain-1 substrate that generates a fluorescent signal upon cleavage was attached to this nanoscale polymeric carrier to generate an engineered TBI-ABN. When applied intravenously to a mouse model of TBI, our engineered sensor is observed to locally activate in the injured brain tissue. This TBI-ABN is the first demonstration of a sensor that responds to protease activity to detect TBI

Investigation and comparison of multi-state and two-state atom laser output-couplers

We investigate the spatial structure and temporal dynamics created in a Bose-Einstein condensate (BEC) by radio-frequency (RF) atom laser output-couplers using a one-dimensional mean-field model. We compare the behavior of a `pure' two-state atom laser to the multi-level systems demonstrated in laboratories. In particular, we investigate the peak homogeneous output flux, classical fluctuations in the beam and the onset of a bound state which shuts down the atom laser output.Comment: 9 pages, 8 figure

A retrospective study of patient outcomes and satisfaction following pinnaplasty

Introduction: Up to 5% of all children have prominent ears. Psychological distress and bullying adversely affect these children and can cause significant social exclusion. In times of austerity, cosmetic procedures such as surgical correction of prominent ears are felt to be an unnecessary cost to the health service. Materials and methods: A retrospective case note review of all patients undergoing pinnaplasty was undertaken. Postoperative outcomes were compared against the Royal College of Surgeons of England standards. The Glasgow Benefit Inventory, a validated post-intervention questionnaire, was then posted out to all patients. Results: A total of 72 patients were identified. Average age at procedure was 13 years. Eleven patients were above the age of 19 years. Twenty-eight patients were male and forty-four female. Sixty-two cases underwent bilateral pinnaplasty. No patients developed hematoma, and there were no readmissions within 30 days of surgery. Twenty-nine patients responded to the questionnaire (40%), of whom 27 reported a positive impact on their psychosocial well-being with a mean score of 36. Conclusion: Pinnaplasty offers patients an opportunity to alleviate the psychological distress of bullying and harassment secondary to the appearance of prominent ears

Modelling the hepatitis B vaccination programme in prisons

A vaccination programme offering hepatitis B (HBV) vaccine at reception into prison has been introduced into selected prisons in England and Wales. Over the coming years it is anticipated this vaccination programme will be extended. A model has been developed to assess the potential impact of the programme on the vaccination coverage of prisoners, ex-prisoners, and injecting drug users (IDUs). Under a range of coverage scenarios, the model predicts the change over time in the vaccination status of new entrants to prison, current prisoners and IDUs in the community. The model predicts that at baseline in 2012 57% of the IDU population will be vaccinated with up to 72% being vaccinated depending on the vaccination scenario implemented. These results are sensitive to the size of the IDU population in England and Wales and the average time served by an IDU during each prison visit. IDUs that do not receive HBV vaccine in the community are at increased risk from HBV infection. The HBV vaccination programme in prisons is an effective way of vaccinating this hard-to-reach population although vaccination coverage on prison reception must be increased to achieve this

Inversion of surficial sediment thickness from under-ice acoustic transmission measurement

Author Posting. © Acoustical Society of America, 2021. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 149(1), (2021): 371, https://doi.org/10.1121/10.0003328.The under-ice acoustic transmission experiment of 2013, conducted under ice cover in the Fram Strait, was analyzed for bottom interactions for the purpose of developing a model of the seabed. Using the acoustic signals, as well as data from other sources, including cores, gravimetric, refraction, and seismic surveys, it was deduced that the seabed may be modeled as a thin surficial layer overlaid on a deeper sediment. The modeling was based on the Biot–Stoll model for acoustic propagation in porous sediments, aided by more recent developments that improve parameter estimation and depth dependence due to consolidation. At every stage, elastic and fluid approximations were explored to simplify the model and improve computational efficiency. It was found the surficial layer could be approximated as a fluid, but the deeper sediment required an elastic model. The full Biot–Stoll model, while instrumental in guiding the model construction, was not needed for the final computation. The model could be made to agree with the measurements by adjusting the surficial layer thickness.The fieldwork was performed under funding from the Research Council of Norway through the UNDER-ICE (Grant No. 226373) project and ENGIE E&P Norway providing additional support. This analysis was supported by the United States Office of Naval Research, Ocean Acoustics Program.2021-07-1

Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study

Breast cancer; Pharmacogenomics; Tumour biomarkersCáncer de mama; Farmacogenómica; Biomarcadores tumoralesCàncer de mama; Farmacogenòmica; Biomarcadors tumoralsThese analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2-mutation carriers. In the evaluable intent-to-treat population (N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non-BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2-mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non-BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial.In Manchester, this trial was undertaken in/supported by the NIHR Manchester Clinical Research Facility at The Christie Hospital NHS Foundation Trust. The ABRAZO study was sponsored by Medivation, which was acquired by Pfizer in September 2016 (grant number not applicable). The authors wish to thank Masaki Mihaila and the Pfizer clinical programming team for the ABRAZO correlative analyses. Medical writing support was provided by Dominic James, PhD, and Hannah Logan, PhD, of CMC AFFINITY, a division of IPG Health Medical Communications, and was funded by Pfizer

Why momentum width matters for atom interferometry with Bragg pulses

We theoretically consider the effect of the atomic source's momentum width on the efficiency of Bragg mirrors and beamsplitters and, more generally, on the phase sensitivity of Bragg pulse atom interferometers. By numerical optimization, we show that an atomic cloud's momentum width places a fundamental upper bound on the maximum transfer efficiency of a Bragg mirror pulse, and furthermore limits the phase sensitivity of a Bragg pulse atom interferometer. We quantify these momentum width effects, and precisely compute how mirror efficiencies and interferometer phase sensitivities vary as functions of Bragg order and source type. Our results and methodology allow for an efficient optimization of Bragg pulses and the comparison of different atomic sources, and will help in the design of large momentum transfer Bragg mirrors and beamsplitters for use in atom-based inertial sensors.Comment: 25 pages, 11 figure