Model for coiling and meandering instability of viscous threads

A numerical model is presented to describe both the transient and steady-state dynamics of viscous threads falling onto a plane. The steady-state coiling frequency w is calculated as a function of fall height H. In the case of weak gravity, w ~ H^{-1} and w ~ H are obtained for lower and higher fall heights respectively. When the effect of gravity is significant, the relation w ~ H^2 is observed. These results agree with the scaling laws previously predicted. The critical Reynolds number for coil-uncoil transition is discussed. When the gravity is weak, the transition occurs with hysteresis effects. If the plane moves horizontally at a constant speed, a variety of meandering oscillation modes can be observed experimentally. The present model also can describe this phenomenon. The numerically obtained state diagram for the meandering modes qualitatively agrees with the experiment.Comment: 12 pages, 10 figure

Cervical cancer prevention in transgender men : a review

Funding MA was supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (grant no.847845)Peer reviewedPostprin

Cohort profile: the DASH (determinants of adolescent social well-being and health) study, an ethnically diverse cohort

No abstract available

AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated speck-like protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Optical and photoelectronic properties of a new material:Optoelectronic application

With the aim of studying the optical, electrochemical, and electronic properties of a new porphyrin-based material, we have synthesized a new porphyrinic complex, namely the (4,4$^{\prime}$-bipyridine)(meso-tetratrifluoromethylphenylporphyrinato)zinc(II) 4,4$^{\prime}$-bipyridine disolvate dihydrate complex with the formula [Zn(TFMPP)(4,4$^{\prime}$-bipy)]${\cdot }$2(4,4$^{\prime}$-bipy)${\cdot }$2H2O (I). This species is characterized by single-crystal X-ray molecular structure. The optical study is performed by UV–visible absorption and fluorescence spectroscopy. The fluorescence intensity presents an emission in the UV–visible range, indicating that this compound can be used as an optoelectronic material. The optical energy gap is 1.95 eV, and the current–voltage characteristics and impedance spectroscopy measurements have been studied to define the electronic properties of the zinc (II) porphyrin complex. The barrier height ${\phi }_{\mathrm{b}}$ is calculated, and the space-charge limited current mechanism is found to control the conductance. The results from the electronic study confirm that our porphyrin derivative can be used for various optoelectronic applications

The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values

Hybridisation and description of the trait-based and empirical selection programs

The hybridization and selection programmes for drought resistance in groundnut, implemented at 4 locations in India (Tirupati, Andhra Pradesh; NRCG [Junagadh, Gujarat]; Jalgaon, Maharashtra; and ICRISAT) and one location in Australia (Kingaroy, Queensland), are described. The trait-based (indirect) selection programme combined high transpiration efficiency, harvest index and transpiration using a Selection Index approach. F1 and F2 plants were grown under non-stressed conditions to maximize seed multiplication. The F3 progenies were divided between trait-based and empirical selection approaches. The F2:3 progeny bulks were evaluated for pod yield, total dry matter, transpiration efficiency, harvest index and transpiration. Some 400 progenies incorporating representative members from each cross were carried forward. The carried-forward F2:4 progeny bulks were grown under stressed and non-stressed conditions, and the aforementioned parameters were re-evaluated. The selected F2:4 progenies were used to generate 5 F2:5 families at each site for each selection method. The replicated field trials were conducted in 2000/01. For the empirical (direct) selection programme, the procedure involved selection for pod yield. The procedure was similar to that of the trait-based selection, except that selections were conducted in an appropriate target environment as chosen by the relevant breeding programme (for example, under rainfed or irrigated conditions at the main experimental site). By the end of the selection cycles, the empirical selection approach supplied a subset of F2:5 progenies for inclusion in multilocation testin

Assessing the safety culture of care homes: a multimethod evaluation of the adaptation, face validity and feasibility of the Manchester Patient Safety Framework

Background: Understanding the cultural characteristics of healthcare organisations is widely recognised to be an important component of patient safety. A growing number of vulnerable older people are living in care homes but little attention has been paid to safety culture in this sector. In this study, we aimed to adapt the Manchester Patient Safety Framework (MaPSaF), a commonly used tool in the health sector, for use in care homes and then to test its face validity and preliminary feasibility as a tool for developing a better understanding of safety culture in the sector. Methods: As part of a wider improvement programme to reduce the prevalence of common safety incidents among residents in 90 care homes in England, we adapted MaPSaF and carried out a multimethod participatory evaluation of its face validity and feasibility for care home staff. Data were collected using participant observation, interviews, documentary analysis and a survey, and were analysed thematically. Results: MaPSaF required considerable adaptation in terms of its length, language and content in order for it to be perceived to be acceptable and useful to care home staff. The changes made reflected differences between the health and care home sectors in terms of the local context and wider policy environment, and the expectations, capacity and capabilities of the staff. Based on this preliminary study, the adapted tool, renamed ‘Culture is Key’, appears to have reasonable face validity and, with adequate facilitation, it is usable by front-line staff and useful in raising their awareness about safety issues. Conclusions: ‘Culture is Key’ is a new tool which appears to have acceptable face validity and feasibility to be used by care home staff to deepen their understanding of the safety culture of their organisations and therefore has potential to contribute to improving care for vulnerable older people