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Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.
Alcohol induced liver disease (ALD) is the predominant cause of alcohol-related mortality in the UK. Therefore helping patients with ALD to quit is a primary treatment goal.
The primary aim of this study was to measure the effectiveness and tolerability of Baclofen in maintaining abstinence, and to determine if this resulted in a reduction in standard measures of liver damage.
An observational prospective clinical audit was performed. Patients with ALD were commenced on Baclofen titrated according to tolerability and response up to 30 mg TDS. Primary outcome measures were severity of physical dependence (SADQ score) and biochemical markers of liver damage GGT, ALT, Bilirubin fibroelastography. These were compared at baseline, and 1 year.
Of the 243 patients commenced on Baclofen, 151 (85 female 66 male) have completed 1 year follow-up (F/U) of which 130 (86%) have remained engaged. 10 have died. Comparison of baseline (B/L) and 1 year biochemical markers showed a reduction in GGT (c2= 66.8 P < 0.0001) and Bil (c2= 82.6 P < 0.0001). There was a significant reduction in alcohol consumption (P < 0.0001 95% CI = 10 to 22). And the presence of physical dependence (c<sup>2</sup> = 77.4 P < 0.0001) as categorised by SADQ.
Baclofen is well tolerated in this very difficult to treat, high risk patient group. It has a positive impact on alcohol consumption, and overall measures of liver function and harm. A RCT is needed to confirm the benefit of Baclofen in this patient group.</div>
Total laryngectomy is often utilised to manage squamous cell carcinoma of the larynx or hypopharynx. This study reports on surgical trends and outcomes over a 10-year period.
A retrospective review of patients undergoing total laryngectomy for squamous cell carcinoma was performed (n = 173), dividing patients into primary and salvage total laryngectomy cohorts.
A shift towards organ-sparing management was observed. Primary total laryngectomy was performed for locoregionally advanced disease and utilised reconstruction less than salvage total laryngectomy. Overall, 11 per cent of patients developed pharyngocutaneous fistulae (primary: 6 per cent; salvage: 20 per cent) and 11 per cent neopharyngeal stenosis (primary: 9 per cent; salvage: 15 per cent). Pharyngocutaneous fistulae rates were higher in the reconstructed primary total laryngectomy group (24 per cent; 4 of 17), compared with primary closure (3 per cent; 3 of 90) (p = 0.02). Patients were significantly more likely to develop neopharyngeal stenosis following pharyngocutaneous fistulae in salvage total laryngectomy (p = 0.01) and reconstruction in primary total laryngectomy (p = 0.02). Pre-operative haemoglobin level and adjuvant treatment failed to predict pharyngocutaneous fistulae development.
Complications remain hard to predict and there are continuing causes of morbidity. Additionally, prior treatment continues to affect surgical outcomes.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Depression frequently co-occurs with disorders of glucose and insulin homeostasis (DGIH) and obesity. Low-grade systemic inflammation and lifestyle factors in childhood may predispose to DGIH, obesity and depression. We aim to investigate the cross-sectional and longitudinal associations among DGIH, obesity and depression, and to examine the effect of demographics, lifestyle factors and antecedent low-grade inflammation on such associations in young people.
Using the Avon Longitudinal Study of Parents and Children birth cohort, we used regression analyses to examine: (1) cross-sectional and (2) longitudinal associations between measures of DGIH [insulin resistance (IR); impaired glucose tolerance] and body mass index (BMI) at ages 9 and 18 years, and depression (depressive symptoms and depressive episode) at age 18 years and (3) whether sociodemographics, lifestyle factors or inflammation [interleukin-6 (IL-6) at age 9 years] confounded any such associations.
We included 3208 participants. At age 18 years, IR and BMI were positively associated with depression. These associations may be explained by sociodemographic and lifestyle factors. There were no longitudinal associations between DGIH/BMI and depression, and adjustment for IL-6 and C-reactive protein did not attenuate associations between IR/BMI and depression; however, the longitudinal analyses may have been underpowered.
Young people with depression show evidence of DGIH and raised BMI, which may be related to sociodemographic and lifestyle effects such as deprivation, smoking, ethnicity and gender. In future, studies with larger samples are required to confirm this. Preventative strategies for the poorer physical health outcomes associated with depression should focus on malleable lifestyle factors.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP).
To investigate the effectiveness of commonly used antipsychotic medications in FEP.
A retrospective cohort study of naturalistic treatment of patients (N = 460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files.
Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation.
Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus.
Nanoenergetic composites are of overwhelming interest to the Department of Defense because of the higher power output and the ability to finely tune the ignition thresholds of these composites. Recently, several variants of a nanoaluminum-poly(perfluorinated methacrylate) (AlFA) have been synthesized and optimized for a variety of applications including reactive warhead liners and bullet spotters. While conventional techniques such as thermal analysis and bomb calorimetry can be used to characterize the reaction mechanism and energy output of AlFA composites, characterizing their dynamic behaviour is more challenging. Bullet spotter applications require a material to be impact sensitive at very low velocities, yet be adequately insensitive. Several live-fire tests were conducted which revealed the AlFA50 material reacted consistently upon target impact at high velocities, but unreliably at very low velocities. In an effort to better understand the fundamental impact ignition mechanism and to determine the impact velocity threshold of AlFA50 a series of Taylor gas gun experiments were conducted. It was determined that the light-initiation mechanism was consistent with a pinch mechanism, and that the ignition velocity threshold was near 74 m/s. Based on these results, it was hypothesized that the addition of a filler material could be used to sensitize the AlFA50, and that Asay shear impact testing could be used to determine a more optimal shape of such inclusions. Experiments performed using the Asay shear impact test setup confirmed the pinch ignition mechanism, but observations also revealed that the size of the pinch point was important. Finally, it was shown that the addition of large glass beads (> 1mm in diameter) was effective at sensitizing the AlFA50 material at high and low velocities, with ignition observed at impact velocities as low as 35 m/s.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
The ablation areas of debris-covered glaciers typically consist of a complex mosaic of surface features with contrasting processes and rates of mass loss. This greatly complicates glacier response to climate change, and increases the uncertainty of predictive models. In this paper we present a series of high-resolution DEMs and repeat lake bathymetric surveys on Ngozumpa Glacier, Nepal, to study processes and patterns of mass loss on a Himalayan debris-covered glacier in unprecedented detail. Most mass loss occurs by melt below supraglacial debris, and melt and calving of ice cliffs (backwasting). Although ice cliffs cover only ~5% of the area of the lower tongue, they account for 40% of the ablation. The surface debris layer is subject to frequent re-distribution by slope processes, resulting in large spatial and temporal differences in debris-layer thickness, enhancing or inhibiting local ablation rates and encouraging continuous topographic inversion. A moraine-dammed lake on the lower glacier tongue (Spillway Lake) underwent a period of rapid expansion from 2001 to 2009, but later experienced a reduction of area and volume as a result of lake level lowering and sediment redistribution. Rapid lake growth will likely resume in the near future, and may eventually become up to 7 km long.
Paleozoic echinoids are exceptionally rare, and little is known of their paleoenvironmental distribution. The echinoid fauna of the Fort Payne Formation (Late Osagean, Early Viséan) of south-central Kentucky is documented. Four genera, ?Archaeocidaris, Lepidocidaris, ?Lepidesthes, and an unidentified lepidocentrid, were recovered and represent three different families. This fauna, and their associated paleoenvironments, give important new insights into the facies distribution of Paleozoic echinoids and the taphonomic biases that affect this distribution. Lepidocidaris is known from the green shale facies, which comprises the core of Fort Payne’s carbonate buildups. ?Archaeocidaris and the lepidocentrid are known from the wackestone buildups and crinoidal packstone buildups. ?Lepidesthes is also known from crinoidal packstone and wackestone buildups, which argues against a semi-infaunal life mode for this taxon. All relatively semiarticulated echinoids were known from autochthonous facies, whereas the only echinoids from the allochthonous facies were disarticulated hemipyramids. Furthermore, deeper-water carbonate buildups were apparently capable of supporting diverse echinoid faunas during the Viséan.
A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid “tetanic” presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual “tetanus,” indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition. (JINS, 2015, 21, 831–840)
Many studies have used retrospective reports to assess the long-term consequences of early life stress. However, current individual characteristics and experiences may bias the recall of these reports. In particular, depressed mood may increase the likelihood of recall of negative experiences. The aim of the study was to assess whether specific factors are associated with consistency in the reporting of childhood adverse experiences.
The sample comprised 7466 adults from Canada's National Population Health Survey who had reported on seven childhood adverse experiences in 1994/1995 and 2006/2007. Logistic regression was used to explore differences between those who consistently reported adverse experiences and those whose reports were inconsistent.
Among those retrospectively reporting on childhood traumatic experiences in 1994/1995 and 2006/2007, 39% were inconsistent in their reports of these experiences. The development of depression, increasing levels of psychological distress, as well as increasing work and chronic stress were associated with an increasing likelihood of reporting a childhood adverse experience in 2006/2007 that had not been previously reported. Increases in mastery were associated with reduced likelihood of new reporting of a childhood adverse experience in 2006/2007. The development of depression and increases in chronic stress and psychological distress were also associated with reduced likelihood of ‘forgetting’ a previously reported event.
Concurrent mental health factors may influence the reporting of traumatic childhood experiences. Studies that use retrospective reporting to estimate associations between childhood adversity and adult outcomes associated with mental health may be biased.
Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity.
In imbibing seeds, resumption of metabolism leads to the unavoidable release of volatile by-products that are perceived as cues by rodent seed predators. The crypsis hypothesis proposes that the primary function of a water-impermeable, hard seed coat is to reduce rodent seed predation by rendering seeds olfactorily cryptic. In an opinion paper, Jayasuriya et al. (2015) find the crypsis hypothesis unscientific and ‘not consistent with Darwin's theory of evolution by natural selection’. It is unfortunate that Jayasuriya et al. (2015) did not appreciate that the crypsis hypothesis offers an alternative explanation for the evolution of water-impermeable seeds: released seed volatiles are cues used by rodents to locate seeds, and variation in seed-coat permeability leading to differences in seed volatile release represents the variable under selection. Furthermore, the sealing of water-impermeable seed coats imposes a cost of increased generation time and, therefore, dormancy-release mechanisms are expected to subsequently evolve in response to local environmental conditions. We also disagree with most other claims by Jayasuriya et al. (2015), who failed to appreciate how species with dimorphic seeds – one morph with permeable and the other with impermeable seed coats – benefit from rodent caching behaviour and population dynamics. We welcome this opportunity to clarify and elaborate on key features and the evolution of water-impermeable seed coats according to the crypsis hypothesis.
Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.
A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the ‘slow tail’ of the distribution).
Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09–0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07–1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60–1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.
Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.
Crinoids were relatively unaffected by the end-Devonian Hangenberg mass extinction event. Major clades of Devonian durophagous fishes suffered significant extinctions, however, and the dominant surviving clades were biting or nipping predators. In part as a response to the Hangenberg event, early Mississippian crinoids underwent an adaptive radiation, while fish clades with a shell-crushing durophagous strategy diversified. Durophagous predators are inferred to have been more effective predators on camerate crinoids; and it is hypothesized, following the predictions of escalation, that through the early Mississippian, camerate crinoids evolved more effective anti-predatory strategies in response. We test this hypothesis of escalation by examining the changes in spinosity and plate convexity among camerate crinoids throughout this interval. A new method was formulated to test for an increase in convexity of the tegmen plates. Traits in Agaricocrinus, Aorocrinus, and Dorycrinus (Family Coelocrinidae) were tested for congruence to the escalation hypothesis, and results were mixed. Convexity of tegmen plates in Agaricocrinus, spine length/calyx diameter in Aorocrinus, calyx size in Aorocrinus, central spine length in Dorycrinus, and spine width in Dorycrinus did not have size increase trends supporting escalation. Rather than an increase in convexity, the variance of convexity in Agaricocrinus tegmen plates narrowed, which could reflect an optimum. Alternatively, morphological change consistent with the escalation hypothesis occurred in calyx size of Agaricocrinus and in lateral spine length and calyx size in Dorycrinus. Furthermore, central and lateral spine length, parameters of the spine width, and size trends support escalation when Aorocrinus and Dorycrinus are treated as a lineage. Thus, inferred escalation acted on traits differently within a single lineage and was relevant for both speciation and the diversification of a new genus.
We must begin with names. ‘Tony Edwards’ is the person to whom this volume is dedicated, but it is not a name that everyone will immediately recognize, particularly those who know him only from his published work, for he has made himself known in public, from the first, as A. S. G. Edwards. When he began his career, this was the manner in which most scholars, most men at least, named themselves. Fashions have changed, and given names, one, two, or more, are now almost universal. But Tony has held on tenaciously to his initials, perhaps because he has three of them. We do not believe that he did so in any spirit of emulation of or desire to align himself with ‘Edwards A. S. G.’, the Edwards Active Strain Gauge well known to Google, an advanced form of technical engineering equipment which guarantees the vacuum conditions needed for the manufacture of certain precision instruments, such as aircraft engine turbine blades. It seems strangely apt as an analogous form of ‘A. S. G.’, whether one thinks of the ‘active strain’ involved as what he exerts upon himself or upon other people. The analogy fails, of course, when one comes to the creation of vacuum, where it works back to front, for Tony's work has essentially been to fill the vacuum that once existed in the study of manuscript history.