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.

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.

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.

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.

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.

Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting LiTMUS baseline data with pre-existing placebo controlled trials.

BACKGROUND: Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The LiTMUS trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. METHOD: To maximize generalizability, LiTMUS used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The LiTMUS study design and baseline sociodemographic data were compared to previous efficacy studies. RESULTS: As compared to the previous bipolar disorder efficacy studies, LiTMUS participants were of similar age, gender, weight and illness severity; however LiTMUS participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. CONCLUSIONS: LiTMUS was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the LiTMUS study to be a more representative of real world pharmacotherapuetic outcomes. LIMITATIONS: Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.

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.

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.

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.

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.

Aims and results of the NIMH systematic treatment enhancement program for bipolar disorder (STEP-BD).

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP-BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP-BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP-BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP-BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.

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.

Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders.

BACKGROUND: The impact of anxiety disorders has not been well delineated in prospective studies of bipolar disorder. AIMS: To examine the association between anxiety and course of bipolar disorder, as defined by mood episodes, quality of life and role functioning. METHOD: A thousand thousand out-patients with bipolar disorder were followed prospectively for 1 year. RESULTS: A current comorbid anxiety disorder (present in 31.9% of participants) was associated with fewer days well, a lower likelihood of timely recovery from depression, risk of earlier relapse, lower quality of life and diminished role function over I year of prospective study. The negative impact was greater with multiple anxiety disorders. CONCLUSIONS: Anxiety disorders, including those present during relative euthymia, predicted a poorer bipolar course. The detrimental effects of anxiety were not simply a feature of mood state. Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course.

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.

The muscarinic receptor agonist xanomeline has an antipsychotic-like profile in the rat.

The muscarinic receptor agonist xanomeline was examined and compared with the antipsychotics clozapine and/or haloperidol in the following in vivo rat models: apomorphine-induced disruption of prepulse inhibition (PPI), amphetamine-induced hyperlocomotion, and the conditioned emotional response (CER) test. The effects of xanomeline were also assessed ex vivo on dopamine turnover in the rat medial prefrontal cortex. Under conditions of varying dose and prepulse intensity, xanomeline, like haloperidol, had no effect on PPI. In contrast, the muscarinic receptor antagonist scopolamine and the muscarinic receptor agonist pilocarpine both induced significant dose-dependent deficits in PPI. Haloperidol and xanomeline, but not pilocarpine, dose dependently reversed apomorphine-induced disruption of PPI. Thus, xanomeline induced a clear antipsychotic-like effect in PPI, whereas pilocarpine appeared to induce a psychotomimetic-like effect. Xanomeline attenuated amphetamine-induced hyperactivity at doses that had no effect on spontaneous activity, possibly indicating a separation between attenuation of limbic hyperdopaminergic function and the induction of hypolocomotion. Haloperidol and clozapine also reversed amphetamine-induced hyperlocomotion, but at similar doses to those that reduced spontaneous locomotion. Clozapine, but not haloperidol had an anxiolytic-like effect in the CER test. The effects of xanomeline in the CER test were similar to those of clozapine, although at the anxiolytic dose it tended to disrupt baseline levels of lever pressing. Finally, haloperidol, clozapine, pilocarpine, and xanomeline, all induced an increase in dopamine turnover in medial prefrontal cortex. The antipsychotic-like effects of xanomeline in the animal models used here suggest that it may be a useful treatment for psychosis.

Evaluation of the All Stars character education and problem behavior prevention program: effects on mediator and outcome variables for middle school students.

The effects of All Stars, a character education and problem behavior prevention program, on variables theorized to mediate problem behaviors and on the problem behavior variables of substance use, sexual behavior, and violence among middle school students are reported. In an independent, randomized, single-cohort, longitudinal evaluation of the program, 1,655 students completed pretest, posttest, and 1-year follow-up surveys measuring demographics, mediating variables, and behavioral outcome variables. Results indicate that the All Stars program, when administered by teachers, had an immediate effect on mediating variables that did not persist over time. Inclusion of ethnicity in the design showed that the program, when administered by specialists, had delayed effects on mediating variables for African American and Hispanic students. However, no consistent effects were found for student problem behaviors in either condition. Implications for prevention practice and directions for future research are discussed.

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.