Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS).

This study was designed to identify genes whose expression in peripheral blood may serve as early markers for treatment response to lithium (Li) in patients with bipolar disorder. Although changes in peripheral blood gene-expression may not relate directly to mood symptoms, differences in treatment response at the biochemical level may underlie some of the heterogeneity in clinical response to Li. Subjects were randomized to treatment with (n=28) or without (n=32) Li. Peripheral blood gene-expression was measured before and 1 month after treatment initiation, and treatment response was assessed after 6 months. In subjects treated with Li, 62 genes were differentially regulated in treatment responders and non-responders. Of these, BCL2L1 showed the greatest difference between Li responders and non-responders. These changes were specific to Li responders (n=9), and were not seen in Li non-responders or patients treated without Li, suggesting that they may have specific roles in treatment response to Li.

General medical burden in bipolar disorder: findings from the LiTMUS comparative effectiveness trial.

OBJECTIVE: This study examined general medical illnesses and their association with clinical features of bipolar disorder. METHOD: Data were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively. RESULTS: The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive-compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14). CONCLUSION: The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.

Medication adherence in a comparative effectiveness trial for bipolar disorder.

OBJECTIVE: Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (range 20-64%). We examined medication adherence in a multisite, comparative effectiveness study of lithium. METHOD: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared with optimized treatment in adult out-patients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. RESULTS: We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (<7%). Poor medication adherence was associated with more manic symptoms and side-effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. CONCLUSION: Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence.

Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.

OBJECTIVES: Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies. We aimed to determine strain diversity, adaptation mechanisms, and AMR features to better inform treatment. METHODS: P. aeruginosa from 180 bronchiectasis patients in 15 countries, obtained prior to a phase 3, randomised clinical trial (ORBIT-3), were analysed by whole-genome sequencing. Phylogenetic groups and sequence types were determined, and between versus within patient genetic diversity compared using Analysis of Molecular Variance (AMOVA). The frequency of AMR-associated genes and mutations was also determined. RESULTS: A total of 2854 P. aeruginosa isolates were analysed, predominantly belonging to phylogenetic group 1 (83%, n = 2359). Genetic diversity was far greater between than within patients, responsible for >99.9% of total diversity (AMOVA: phylogroup 1: df = 145, P < 0.01). Numerous pathways were under selection, some shared with CF (e.g., motility, iron acquisition), some unique to bronchiectasis (e.g., novel efflux pump PA1874). Multidrug resistance features were also frequent. CONCLUSIONS: We present a 10-fold increase in the availability of genomic data for P. aeruginosa in bronchiectasis, highlighting key distinctions with cystic fibrosis and potential targets for future treatments.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Blood culture and stimulation conditions for the diagnosis of tuberculosis in cervids by the Cervigam assay.

Mitogen- and antigen-induced interferon-gamma (IFN-gamma) responses of peripheral blood leucocytes from cervids were evaluated by a commercial whole-blood assay. The assay was applied to Mycobacterium bovis-infected white-tailed deer and reindeer, M bovis BCG-vaccinated white-tailed deer and elk, and unvaccinated, uninfected white-tailed deer, fallow deer, elk and reindeer. The responses of the M bovis-infected white-tailed deer to pokeweed mitogen (PWM) varied with time and between individuals. The responses of the M bovis-infected reindeer to PWM and M bovis purified protein derivative (PPD) were positively associated. Samples from tuberculosis-free captive herds in various parts of the USA were also evaluated. Four per cent of fallow deer, 20 per cent of elk, 44 per cent of white-tailed deer, and 91 per cent of reindeer had responses to PWM exceeding 0.25 Delta optical density, that is, PWM stimulation minus no stimulation. The specificity of the responses to M bovis PPD and a Mycobacterium tuberculosis complex-specific antigen rESAT-6:CFP-10, excluding animals not responding to PWM, ranged from 78 per cent to 100 per cent and was dependent upon the species and the positive response cut-off value. The results show that the commercial assay is valid for the detection of TB in reindeer; however, further development of the assay will be required before it is used in surveillance programmes for white-tailed deer, fallow deer, and elk.

Effects of creating a non-specific, virus-hostile environment in the nasopharynx on symptoms and duration of common cold.

The Common Cold remains the most frequent symptomatic viral infection in man. Current best therapies are all symptomatic. New pharmacological therapies are likely to be prescription-bound, and as most Common Cold infections are successfully treated without the intervention of a Physician, there is a need for effective non-prescription therapy options. Aim of this study is to propose a new type of approach, based on the concept of making a hostile biological environment for virus survival and spreading at the point of infection, the nasopharynx. The hypothesis was advanced that infections could be controlled using a physical biological approach to create an environment at the point of infection, that is inhibitory to the survival, and persistence of infecting virus, and of viruses newly released from infected mucosal epithelial cells. A nasal irrigation spray, designed to deliver a low pH gel to the nasal cavity, was developed and tested in this study. The study was a randomised, parallel, double-blind, placebo-controlled evaluation of three formulations of irrigation nasal spray in 441 subjects. The objective was to test whether the formulations reduced Cold severity and Cold duration compared to a placebo nasal spray. Subjects were recruited, and supplied with the product when healthy, and were instructed to begin treating and recording symptom severity once they experienced the "first signs" of a Common Cold. To qualify, subjects had to volunteer that they had at least one of the symptoms: sore/scratchy throat, runny nose or congested nose. The product was used 4 times daily, with at least 4 hours separating each dose, for a maximum of 7 days. Efficacy was assessed by an Interactive Voice Recall System whereby subjects were required to contact the investigation site, by telephone, twice daily when they were asked to assess the severity of their symptoms using a four point ordinal scale where 0 = "absent", and 3 = "severe". The symptoms assessed were sore throat, runny nose, blocked nose, cough and tired/run-down feeling. Two formulations demonstrated significant effects. A hydroxy methyl propyl cellulose based formulation reduced symptom severity compared with placebo by 17% and a Poloxamer based formulation reduced severity by 21%. Duration of illness was reduced with a hydroxy methyl propyl cellulose based formulation by 1.5 days to 2.4 days (according to the dose) and by a Poloxamer based formulation by 2.5 days. Results of this study suggest that the creation of a non virus-specific, inhibitory environment in the nasopharynx holds promise as an effective method of controlling the severity and duration of the Common Cold.

Dental treatment in children with asthma - a review.

This article aims to explain the effects of long-term use of asthma medications. It will discuss the effects of asthma on the oral cavity, as well considerations for the dentist when treating asthmatic patients. It will also explain how to manage asthma in the dental setting and provide advice on maintaining oral health for asthmatic patients.

Dental treatment for people with cystic fibrosis.

AIM: To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients. METHODS: A literature search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner. RESULTS: Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care. CONCLUSION: The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.

Lamotrigine has an anxiolytic-like profile in the rat conditioned emotional response test of anxiety: a potential role for sodium channels?

RATIONALE: Many anticonvulsants are used in disorders other than epilepsy. For example, lamotrigine is reported to be effective in post-traumatic stress disorder and mania. OBJECTIVE: We assessed the effects of the anticonvulsants lamotrigine, valproate and carbamazepine in an animal model of anxiety. We assessed a wide range of pharmacological tools to delineate the mechanism of lamotrigine's anxiolytic effect. METHODS: We assessed these compounds in the rat conditioned emotional response (CER) test of anxiety. RESULTS: Lamotrigine (30-80 mg/kg) dose-dependently and reproducibly engendered an anxiolytic response in this test, with similar efficacy to benzodiazepines. Carbamazepine (20-40 mg/kg) and riluzole (10 mg/kg), which block Na+ channels by a similar mechanism as lamotrigine, were also anxiolytic. By contrast, valproate (100-600 mg/kg) was inactive and appears to differ in its interaction with Na+ channels. The SSRI paroxetine, the GABA(A) receptor positive modulator propofol, the NMDA antagonists memantine and (+)MK-801, and the Ca2+ channel antagonist nifedipine were all inactive in the CER test, suggesting these mechanisms may not mediate the anxiolytic effect of lamotrigine. More directly, we showed that the anxiolytic effect of lamotrigine could be blocked by co-administering rats with the Na+ channel activator veratrine (0.1 mg/kg). By contrast, neither the Ca2+ channel agonist BAYK8644 (0.5 mg/kg) nor the 5-HT1A or 5-HT(1/2) antagonists WAY100635 (0.3 mg/kg) and metergoline (3 mg/kg), respectively, were able to block the effect. CONCLUSION: Lamotrigine's anxiolytic effect in the CER test may be mediated via block of Na+ channels, and this may represent a target for the development of novel anxiolytics.

Illness-induced context aversion learning in rats with lesions of the dorsal hippocampus.

In 2 experiments, rats with electrolytic lesions of the dorsal hippocampus and sham-operated control subjects were given injections of lithium chloride after exposure to a distinctive context. This procedure establishes a context-illness association in intact subjects. In Experiment 1, the strength of the context aversion was assessed by measuring the subjects' willingness to consume a novel flavor in the context. It was found that lesioned subjects showed less suppression of consumption than controls. Experiment 2 tested the ability of the context to block subsequent flavor-aversion learning and revealed less effective blocking in lesioned rats. These results are consistent with the view that hippocampal lesions retard context conditioning; unlike previous work that has made use of conditioned freezing as the measure of context conditioning, the present results are not explicable in terms of lesion-induced changes in general activity.

Nucleus accumbens lesions impair context, but not cue, conditioning in rats.

Previous work has provided evidence of a role for the hippocampal formation in contextual as opposed to cue conditioning. Similar deficits have been observed after transection of the fimbria/fornix, part of which consists of the hippocampal-nucleus accumbens (N.Acc) connection arising from both the dorsal and ventral subiculum. By means of electrolytic lesions of the N.Acc, we showed that the subiculo-accumbens projection appears to participate in aversive conditioning to context, but not to a cue (tone). Freezing, measured as an index of learning, in the experimental context was greatly reduced in animals with lesions of the N.Acc, as compared with sham-operated controls. No difference was found in freezing to a distinct tone. These data lend further support to the notion that the N.Acc is an important interface between limbic structures and motor output.

Psychobiology of novelty seeking and drug seeking behavior.

There is considerable evidence that high novelty seekers are at increased risk for using drugs of abuse relative to low novelty seekers. This review examines the potential biological mechanism that may help explain the relationship between novelty seeking and drug seeking behavior. Evidence is summarized to suggest that exposure to novelty activates, at least in part, the same neural substrate that mediates the rewarding effects of drugs of abuse. It is argued that individual differences in response to novelty and drugs may relate to individual differences in the mesolimbic dopamine (DA) system of the brain. Individual differences in both novelty seeking and drug seeking behavior, while under some degree of genetic control, appear to be modifiable by early development experiences and this modification may relate to alterations in activity of the mesolimbic DA system. Within the context of this biological formulation, implications for the prevention and treatment of drug abuse are discussed.

Task-specific enhancement of short-term, but not long-term, memory by class I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid in rats.

Pharmacological application of broad agonists and antagonists has supported the notion of a potential role of metabotropic glutamate receptors (mGluRs) in learning and memory formation, but the specific function of the different classes or individual subtypes remains elusive. Furthermore, our knowledge with respect to different learning mechanisms is still fragmentary. In an attempt to clarify further the function of mGluRs in learning, rats were trained in various paradigms in the presence/absence of the specific class I antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA). Intraperitoneal application of AIDA prior to training led to enhanced within-session performance in animals trained in a positively reinforced reference memory task in a three-choice maze. However, this enhancement did not result in increased retention as measured by the number of correct responses during the first four trials of each session on subsequent days. The increase was purely an enhancement in within-session performance, required doses higher than 2 mg/kg, and was not accompanied by an unspecific increase in activity as monitored in the open field. By contrast, AIDA animals trained in a combined shock-reinforced contextual and cue conditioning paradigm demonstrated a pronounced retention deficit compared with controls in conditioning to the context, but not the cue (a high-frequency tone). Although within-session performance during context and cue periods was slightly increased in the AIDA group, the difference did not reach significance. Drug-induced hyperactivity, which could account for the memory deficit, was excluded by recordings of activity in specific activity cages. These results shed new light on the possible function of class I mGluRs in learning and memory formation and imply that systemic blockade of class I mGluRs may enhance short-term memory under certain learning conditions.

Cognitive styles and life events interact to predict bipolar and unipolar symptomatology.

This study examined the interaction of cognitive style (as assessed self-report and information-processing battery) and stressful life events in predicting the clinician-rated depressive and manic symptomatology of participants with Research Diagnostic Criteria lifetime diagnoses of bipolar disorder (n = 49), unipolar depression (n = 97), or no lifetime diagnosis (n = 23). Bipolar and unipolar participants' attributional styles, dysfunctional attitudes, and negative self-referent information processing as assessed at Time 1 interacted significantly with the number of negative life events that occurred between Times 1 and 2 to predict increases in depressive symptoms from Time 1 to Time 2. Within the bipolar group, participants' Time 1 attributional styles and dysfunctional attitudes interacted significantly, and their self-referent information processing interacted marginally, with intervening life events to predict increases in manic symptoms from Time 1 to Time 2. These findings provide support for the applicability of cognitive vulnerability-stress theories of depression to bipolar spectrum disorders.

Differences in alcohol use and alcohol-related problems among fraternity and sorority members.

This study examined gender differences in alcohol consumption and problem behaviors among fraternity and sorority college students. Males were more likely to drink 13+ drinks at one time; females were more likely to drink 1-3, 4-6, and 7-12 drinks. Females experienced more problems at the 4-6 level; number of problems experienced were approximately equal at the 7-12 and 13+ levels. The correlation between consumption and problems was stronger for females (r = 0.58) than for males (r = 0.42). Problem behaviors might be due to individual differences or environmental forces acting upon individuals. Longitudinal studies should investigate possible causal pathways to inform the design of interventions for this at-risk population.

Dementia and its associations in type 2 diabetes mellitus: the Fremantle Diabetes Study.

BACKGROUND: recent studies indicate that diabetes is an important risk factor for dementia in older patients, but the cause remains unknown. OBJECTIVES: to determine whether vascular or diabetes-related risk factors predict the development of dementia in older subjects with diabetes. PATIENTS: 63 patients with type 2 diabetes of mean age 75.3 years. METHODS: Subjects were screened for cognitive impairment using the Mini-Mental State Examination (MMSE) and informants who knew the subjects answered the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). Probable dementia was diagnosed using highly specific criteria based on the combination of both tests. Potential risk factors for dementia obtained at the time of the cognitive test and annually from a median of 3.2 years previously were examined using univariate methods and simple general linear modelling. RESULTS: since there was a significant association between MMSE and English speaking ability, ten non-Anglo-Celt patients were excluded from the analysis. Probable dementia was diagnosed in six of the remaining 53 subjects (11%). Dementia was significantly and independently associated with higher diastolic and mean arterial blood pressure measurements over the 3 years before assessment. Blood pressure declined over this time in the patients with probable dementia and was similar to that in non-demented subjects at the time of cognitive assessment. CONCLUSIONS: these preliminary data suggest that the high rate of dementia found in older people with diabetes may be explained by the high rate of hypertension in this population.