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A small spherical source discharges a fluid into a porous medium that is already fully saturated with another fluid. The injected fluid has higher density than the ambient fluid, and so it forms a plume that moves downward under the effects of gravity. We present a simple asymptotic analysis assuming the two fluids do not mix that gives the width of the plume far from the source as a function of the injected volume flux. A spectral method is then developed for solving the full nonlinear problem in Boussinesq theory. Accurate numerical solutions are presented, which show in detail the evolution of the plume of heavier injected fluid over time. Close agreement with the asymptotic plume shape far from the source is demonstrated at later times.

The classical Rayleigh–Taylor instability occurs when a heavy fluid overlies a lighter one, and the two fluids are separated by a horizontal interface. The configuration is unstable, and a small perturbation to the interface grows with time. Here, we consider such an arrangement for planar flow, but in a porous medium governed by Darcy’s law. First, the fully saturated situation is considered, where the two horizontal fluids are separated by a sharp interface. A classical linearized theory is reviewed, and the nonlinear model is solved numerically. It is shown that the solution is ultimately limited in time by the formation of a curvature singularity at the interface. A partially saturated Boussinesq theory is then presented, and its linearized approximation predicts a stable interface that merely diffuses. Nonlinear Boussinesq theory, however, allows the growth of drips and bubbles at the interface. These structures develop with no apparent overturning at their heads, unlike the corresponding flow for two free fluids.

There was no Reichstag fire. No storming of the Bastille. No mutiny on the Aurora. Instead, the mediocre have seized power without firing a single shot. They rose to power on the tide of an economy where workers produce assembly-line meals without knowing how to cook at home, give customers instructions over the phone that they themselves don't understand, or sell books and newspapers that they never read. Canadian intellectual juggernaut Alain Deneault has taken on all kinds of evildoers: mining companies, tax-dodgers, and corporate criminals. Now he takes on the most menacing threat of all: the mediocre.

The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.

The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival.

Aims/Objectives/BackgroundFractured neck of femur is a common presentation and is associated with high rates of morbidity and mortality. RCEM Best Practice specifies that Fascia Iliaca Block should be available in Emergency Departments as part of the pain management strategy.AimsImprove compliance with RCEM guidance for safe administration, documentation and post-procedure monitoring following FIB.Employ QIP methodology to create a FIB protocol.Empower the junior SHO workforce to gain competence in FIB administration through structured teaching.Improve understanding of post-block monitoring in nursing and medical staff.Methods/DesignData collection identified the number of blocks administered to those presenting with fractured neck of femur in November 2019. Documentation and post-procedure monitoring were evaluated.Interventions were piloted in January 2020. These were: pre-made block packs, a block checklist sticker incorporating post-procedure monitoring chart and laminated ‘quick prompt’ guide.Nurse champions facilitated MDT teaching sessions and junior SHOs were empowered to gain competence in block administration through teaching sessions.Retrospective data from January 2020 was compared to November 2019, allowing us to establish the efficacy of changes.Abstract 127 Figure 1Results/ConclusionsOctober 2019 results demonstrated 59% of patients received a FIB, this increased to 78% in January 2020. Pre-intervention, 45% of patients had the correct dose of local anaesthetic. This increased to 79% post-intervention. Initially, documentation was correct in just 5% of cases, improving to 59% after re-auditing.Feedback from teaching sessions was positive with nursing staff better understanding the need for post-procedure monitoring. SHOs gained increased confidence delivering FIBs, freeing up senior doctors for other tasks.The new protocol has improved the administration of FIBs with better post-procedure care and standardised dosing of local anaesthetic. Interventions are embedded in departmental practice; this will be re-audited in 6 months. Following the transition to e-noting we are developing an electronic template to translate these successes onto the new system.

The Berg Balance Scale (BBS) is a balance measure commonly used for people with multiple sclerosis (MS). The Mini-BESTest is an alternative based on balance systems. The study objective was to compare the BBS and the Mini-BESTest for sensitivity to change, likelihood ratios for walking aid use and falls, and associations with clinical variables in people who have MS and are ambulatory. This was a cohort study with measurements before and after exposure to 8 weeks of routine physical therapy intervention. For 52 participants who had a primary diagnosis of MS and who were independently mobile, with or without an aid, demographic details and a history of falls and near falls were collected. Participants completed the Mini-BESTest, Multiple Sclerosis Impact Scale-29, Multiple Sclerosis Walking Scale-12, BBS, Modified Fatigue Impact Scale, and Six-Minute Walk Test. No participant started with a baseline Mini-BESTest maximum score of 28, whereas 38.5% (n=20) started with a baseline BBS maximum score of 56. Statistically significant changes in the Mini-BESTest score (X̅=5.31, SD=3.5) and the BBS score (X̅=1.4, SD=1.9) were demonstrated. Effect sizes for the Mini-BESTest and the BBS were 0.70 and 0.37, respectively; standard response means for the Mini-BESTest and the BBS were 1.52 and 0.74, respectively. Areas under the receiver operating characteristic curves for the Mini-BESTest and the BBS were 0.88 and 0.77, respectively, for detecting mobility device use and 0.88 and 0.75, respectively, for detecting self-reported near falls. The Mini-BESTest had a higher correlation for each secondary measure than did the BBS. This study involved a sample of convenience; 61% of the participants did not use a walking aid. The order of testing was not randomized, and fall status was obtained through retrospective recall. The Mini-BESTest had a lower ceiling effect and higher values on responsiveness tests. These findings suggest that the Mini-BESTest may be better at detecting changes in balance in people who have MS, are ambulatory, and have relatively little walking disability.

Sox18 as a lymphatic switch Mutations in the Sox18 transcription factor gene cause lymphatic dysfunction in the rare human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that it may play a role in lymphatic development of function. That role has now been identified: Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells via the direct activation of transcription of the Prox1 lymphatic marker in lymphatic precursor cells of the embryonic venous system. This suggests possible new strategies for therapeutic stimulation or suppression of lymphoangiogenesis. A role for Sox18 transcription factor has been suggested by lymphatic dysfunction in the human syndrome hypotrichosis-lymphedema-telangiectasia (HLT), which is caused by mutations in Sox18 . This paper shows that Sox18 directly activates Prox1 transcription. Sox18 -null embryos show a complete absence of Prox1 -positive lymphatic endothelial cells emanating from the cardinal vein. The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia 1 , 2 , 3 . However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4 ). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia 5 , suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18 -null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies.

The prevalence of tumours of the germ line is increasing in the male population. This complex disease has a complex aetiology. We examine the contribution of genetic mutations to the development of germ line tumours in this review. In particular, we concentrate on fly and mouse experimental systems in order to demonstrate that mutations in some conserved genes cause pathologies typical of certain human germ cell tumours, whereas other mutations elicit phenotypes that are unique to the experimental model. Despite these experimental systems being imperfect, we show that they are useful models of human testicular germ cell tumourigenesis.

Queer Methods and Methodologies provides the first systematic consideration of the implications of a queer perspective in the pursuit of social scientific research. This volume grapples with key contemporary questions regarding the methodological implications for social science research undertaken from diverse queer perspectives, and explores the limitations and potentials of queer engagements with social science research techniques and methodologies. With contributors based in the UK, USA, Canada, Sweden, New Zealand and Australia, this truly international volume will appeal to anyone pursuing research at the intersections between social scientific research and queer perspectives, as well as those engaging with methodological considerations in social science research more broadly.