Combinatorial Pharyngeal Taste Coding for Feeding Avoidance in Adult Drosophila.

Taste drives appropriate food preference and intake. In Drosophila, taste neurons are housed in both external and internal organs, but the latter have been relatively underexplored. Here, we report that Poxn mutants with a minimal taste system of pharyngeal neurons can avoid many aversive tastants, including bitter compounds, acid, and salt, suggesting that pharyngeal taste is sufficient for rejecting intake of aversive compounds. Optogenetic activation of selected pharyngeal bitter neurons during feeding events elicits changes in feeding parameters that can suppress intake. Functional dissection experiments indicate that multiple classes of pharyngeal neurons are involved in achieving behavioral avoidance, by virtue of being inhibited or activated by aversive tastants. Tracing second-order pharyngeal circuits reveals two main relay centers for processing pharyngeal taste inputs. Together, our results suggest that the pharynx can control the ingestion of harmful compounds by integrating taste input from different classes of pharyngeal neurons

Sea level driven marsh expansion in a coupled model of marsh erosion and migration

Coastal wetlands are among the most valuable ecosystems on Earth, where ecosystem services such as flood protection depend nonlinearly on wetland size and are threatened by sea level rise and coastal development. Here we propose a simple model of marsh migration into adjacent uplands and couple it with existing models of seaward edge erosion and vertical soil accretion to explore how ecosystem connectivity influences marsh size and response to sea level rise. We find that marsh loss is nearly inevitable where topographic and anthropogenic barriers limit migration. Where unconstrained by barriers, however, rates of marsh migration are much more sensitive to accelerated sea level rise than rates of edge erosion. This behavior suggests a counterintuitive, natural tendency for marsh expansion with sea level rise and emphasizes the disparity between coastal response to climate change with and without human intervention

The SSVEP tracks attention, not consciousness, during perceptual filling-in

Research on the neural basis of conscious perception has almost exclusively shown that becoming aware of a stimulus leads to increased neural responses. By designing a novel form of perceptual filling-in (PFI) overlaid with a dynamic texture display, we frequency-tagged multiple disappearing targets as well as their surroundings. We show that in a PFI paradigm, the disappearance of a stimulus and subjective invisibility is associated with increases in neural activity, as measured with steady-state visually evoked potentials (SSVEPs), in electroencephalography (EEG). We also find that this increase correlates with alpha-band activity, a well-established neural measure of attention. These findings cast doubt on the direct relationship previously reported between the strength of neural activity and conscious perception, at least when measured with current tools, such as the SSVEP. Instead, we conclude that SSVEP strength more closely measures changes in attention.</p

The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation

<p>Abstract</p> <p>Background</p> <p>Activated microglia are a feature of the host response to neurodegeneration in Parkinson's disease (PD) and are thought to contribute to disease progression. Recent evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of PD and that this may be mediated by a microglial response.</p> <p>Methods</p> <p>We wished to discover whether the host response to eSNCA would be sufficient to induce significant cytokine production. <it>In vitro </it>cultured BV-2 microglia were used to determine the basic inflammatory response to eSNCA. <it>In vivo</it>, 8-week old Biozzi mice were subjected to a single intranigral injection of either 3 μg SNCA, lipopolysaccharide (LPS) or serum protein (BSA) and allowed to recover for 24 hours. A second cohort of animals were peripherally challenged with LPS (0.5 mg/kg) 6 hours prior to tissue collection. Inflammation was studied by quantitative real-time PCR for a number of pro-inflammatory genes and immunohistochemistry for microglial activation, endothelial activation and cell death.</p> <p>Results</p> <p><it>In vitro </it>data showed a robust microglial response to SNCA, including a positive NFĸB response and the production of pro-inflammatory cytokines. Direct injection of SNCA into the substantia nigra resulted in the upregulation of mRNA expression of proinflammatory cytokines, the expression of endothelial markers of inflammation and microglial activation. However, these results were significantly different to those obtained after direct injection of LPS. By contrast, when the animals were injected intracerebrally with SNCA and subsequently challenged with systemic LPS, the level of production of IL-1β in the substantia nigra became comparable to that induced by the direct injection of LPS into the brain. The injection of albumin into the nigra with a peripheral LPS challenge did not provoke the production of a significant inflammatory response. Direct injection of LPS into the substantia nigra also induces cell death in a more robust manner than direct injection of either SNCA or BSA.</p> <p>Conclusion</p> <p>These results suggest that the presence of eSNCA protein 'primes' microglia, making them susceptible to environmental proinflammatory challenge. For this reason, we hypothesise that where 'inflammation' contributes to the disease progression in PD, it does so in a punctuate manner (on-off) as a result of systemic events.</p

Isolated displaced non-union of a triquetral body fracture: a case report

<p>Abstract</p> <p>Introduction</p> <p>Fractures of the body of the triquetral bone are the second most common carpal fractures, and these fractures can be missed on plain X-ray. Although non-union of triquetral body fractures is very rare, such cases are associated with considerable morbidity and reduction in functional activity.</p> <p>Case presentation</p> <p>We report the case of a 29-year-old Caucasian British man who sustained an isolated displaced triquetral body fracture that resulted in non-union, who was treated surgically. We describe an original operative management for this debilitating injury. An open reduction and internal fixation using double headed compression screws was performed, without bone grafting, and with early immobilization of the wrist.</p> <p>Conclusions</p> <p>We propose this novel approach and advocate early clinical suspicion of triquetral body fractures in patients with a history of fall on an outstretched hand and ulnar sided wrist pain. We recommend evaluation using computed tomography or magnetic resonance imaging scanning.</p

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain:A database analysis to determine recruitment feasibility for a clinical trial

BACKGROUND: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. AIM: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. DESIGN: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. SETTING/PARTICIPANTS: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. RESULTS: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62–77); negatively skewed (−0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996–1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m(2) in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. CONCLUSIONS: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription

Algorithmic Pirogov-Sinai theory

We develop an efficient algorithmic approach for approximate counting and sampling in the low-temperature regime of a broad class of statistical physics models on finite subsets of the lattice $\mathbb Z^d$ and on the torus $(\mathbb Z/n \mathbb Z)^d$. Our approach is based on combining contour representations from Pirogov-Sinai theory with Barvinok's approach to approximate counting using truncated Taylor series. Some consequences of our main results include an FPTAS for approximating the partition function of the hard-core model at sufficiently high fugacity on subsets of $\mathbb Z^d$ with appropriate boundary conditions and an efficient sampling algorithm for the ferromagnetic Potts model on the discrete torus $(\mathbb Z/n \mathbb Z)^d$ at sufficiently low temperature

The comprehensive cohort model in a pilot trial in orthopaedic trauma

Background: The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting. Methods: Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury. Results: At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management. Conclusions: Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions

Vacuum Stability, Perturbativity, and Scalar Singlet Dark Matter

We analyze the one-loop vacuum stability and perturbativity bounds on a singlet extension of the Standard Model (SM) scalar sector containing a scalar dark matter candidate. We show that the presence of the singlet-doublet quartic interaction relaxes the vacuum stability lower bound on the SM Higgs mass as a function of the cutoff and lowers the corresponding upper bound based on perturbativity considerations. We also find that vacuum stability requirements may place a lower bound on the singlet dark matter mass for given singlet quartic self coupling, leading to restrictions on the parameter space consistent with the observed relic density. We argue that discovery of a light singlet scalar dark matter particle could provide indirect information on the singlet quartic self-coupling.Comment: 25 pages, 10 figures; v2 - fixed minor typos; v3 - added to text discussions of other references, changed coloring of figures for easier black and white viewin