One-year outcome of selective caries removal versus pulpotomy treatment of deep caries: A pilot randomized controlled trial.

AIM: This study aimed to compare the outcome of SCR and Pulpotomy in teeth with deep caries extending at least 75% into dentine. METHODOLOGY: This two-armed, parallel-group, randomized, superiority trial included vital mature permanent teeth with deep primary or secondary caries diagnosed radiographically as being at least 75% into the thickness of dentine, without clinical signs of symptomatic irreversible pulpitis or radiographic evidence of a periapical lesion. Carious teeth were blindly allocated to receive either SCR or Pulpotomy using computer-generated randomized patient codes concealed in opaque envelopes. All teeth were reviewed clinically and radiographically at 6 months and 1 year post-treatment. Using a significance level of p < .05, the log rank test and Cox proportional hazards regression were used to compare the outcome of SCR and Pulpotomy and to identify potential prognostic factors, respectively. RESULTS: In all, 58 teeth in the SCR group and 55 teeth in the pulpotomy group completed treatment, after excluding 6 teeth because they did not complete the allocated treatment and another due to severe periodontal disease. At one year, 57/58 (98.3%) teeth from the SCR group and 48/55 (87.3%) teeth from the Pulpotomy group were available for analysis. One tooth in the Pulpotomy group (2.1%) and eight teeth in the SCR group (14.0%) required the further intervention of root canal treatment (p < .05). There were no other significant prognostic factors for survival. Overall, 91.4% of teeth treated with either SCR or Pulpotomy survived without requiring further intervention over a period of one year. No other adverse events occurred over the review period. CONCLUSION: Within the limitations of this study, Pulpotomy fares better than SCR in preserving the remaining pulp and periapical health. As a treatment modality, Pulpotomy carries greater cost outlay to patient and takes a longer time to complete treatment than SCR. Long-term follow-up is needed to study the pulpal and restorative outcomes of Pulpotomy and SCR.

What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis.

BACKGROUND: Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. OBJECTIVE AND RATIONALE: A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. SEARCH METHODS: The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. OUTCOMES: The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. WIDER IMPLICATIONS: Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

Prevalence of alcohol-tolerant and antibiotic-resistant bacterial pathogens on public hand sanitizer dispensers.

BACKGROUND: Since the advent of the COVID-19 pandemic, alcohol-based hand sanitizer dispensers (HSDs) have been installed in most public and clinical settings for hygiene purposes and convenient application. AIM: To determine whether sanitizer-tolerant bacterial pathogens can colonize HSDs, spreading diseases and antibiotic resistance. METHODS: Sampling was conducted from operational automatic HSDs, specifically the dispensing nozzle in direct contact with sanitizer. Culture-dependent cultivation of bacteria and MALDI-TOF were employed to assess microbiological contamination. Bacterial isolates were selected for rapid killing and biofilm eradication assays with alcohol treatment. Antibiotic minimum inhibitory concentration assays were performed according to the Clinical and Laboratory Standards Institute guidelines. Virulence potential of bacterial isolates was evaluated in the Caenorhadbitis elegans infection model. FINDINGS: Nearly 50% of HSDs from 52 locations, including clinical settings, food industry, and public spaces, contain microbial contamination at 103-106 bacteria/mL. Bacterial identification revealed Bacillus cereus as the most frequent pathogen (29%), while Enterobacter cloacae was the only Gram-negative bacterial pathogen (2%). Selecting B. cereus and E. cloacae isolates for further evaluation, these isolates and associated biofilms were found to be tolerant to alcohol with survival up to 70%. They possessed resistance to various antibiotic classes, with higher virulence than laboratory strains in the C. elegans infection model. CONCLUSION: HSDs serve as potential breeding grounds for dissemination of pathogens and antibiotic resistance across unaware users. Proper HSD maintenance will ensure protection of public health and sustainable use of sanitizing alcohols, to prevent emergence of alcohol-resistant pathogens.

No selective integration required: A race model explains responses to audiovisual motion-in-depth.

Looming motion is an ecologically salient signal that often signifies danger. In both audition and vision, humans show behavioral biases in response to perceiving looming motion, which is suggested to indicate an adaptation for survival. However, it is an open question whether such biases occur also in the combined processing of multisensory signals. Towards this aim, Cappe, Thut, Romei, and Murraya (2009) found that responses to audiovisual signals were faster for congruent looming motion compared to receding motion or incongruent combinations. They considered this as evidence for selective integration of multisensory looming signals. To test this proposal, here, we successfully replicate the behavioral results by Cappe et al. (2009). We then show that the redundant signals effect (RSE - a speedup of multisensory compared to unisensory responses) is not distinct for congruent looming motion. Instead, as predicted by a simple probability summation rule, the RSE is primarily modulated by the looming bias in audition, which suggests that multisensory processing inherits a unisensory effect. Finally, we compare a large set of so-called race models that implement probability summation, but that allow for interference between auditory and visual processing. The best-fitting model, selected by the Akaike Information Criterion (AIC), virtually perfectly explained the RSE across conditions with interference parameters that were either constant or varied only with auditory motion. In the absence of effects jointly caused by auditory and visual motion, we conclude that selective integration is not required to explain the behavioral benefits that occur with audiovisual looming motion.

Prediction of delirium using data mining: A systematic review.

Delirium remains a significant cause of morbidity, mortality and economic burden to society. "Big data" refers to data of significantly large volume, obtained from a variety of resources, which is created and processed at high velocity. We conducted a systematic review and meta-analysis exploring whether big data could predict the incidence of delirium of patients in the inpatient setting. Medline, Embase, the Cochrane Library, Web of Science, CINAHL, clinicaltrials.gov, who.int and IEEE Xplore were searched using MeSH terms "big data", "data mining", "delirium" and "confusion" up to 30th September 2019. We included both randomised and observational studies. The primary outcome of interest was development of delirium and the secondary outcomes of interest were type of statistical methods used, variables included in the mining algorithms and clinically important outcomes such as mortality and length of hospital stay. The quality of studies was graded using the CHARMs checklist. Six retrospective single centre observational studies were included (n = 178,091), of which 17, 574 participants developed delirium. Studies were of generally of low to moderate quality. The most commonly studied method was random forest, followed by support vector machine and artificial neural networks. The model with best performance for delirium prediction was random forest, with area under receiver operating curve (AUROC) ranging from 0.78 to 0.91. Sensitivity ranged from 0.59 to 0.81 and specificity ranged from 0.73 to 0.92. Our systematic review suggests that machine-learning techniques can be utilised to predict delirium.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Age-related natural fertility outcomes in women over 35 years: a systematic review and individual participant data meta-analysis.

STUDY QUESTION: What is the rate of natural conception leading to ongoing pregnancy or livebirth over 6-12 months for infertile women of age ≥35 years? SUMMARY ANSWER: Natural conception rates were still clinically relevant in women aged 35 years and above and were significantly higher in women with unexplained infertility compared to those with other diagnoses. WHAT IS KNOWN ALREADY: In recent years, increasing numbers of women have attempted to conceive at a later age, resulting in a commensurate increase in the need for ART. However, there is a lack of data on natural fertility outcomes (i.e. no interventions) in women with increasing age. STUDY DESIGN, SIZE, DURATION: A systematic review with individual participant data (IPD) meta-analysis was carried out. PubMed, MEDLINE, EMBASE, the Cochrane Library, clinicaltrials.gov were searched until 1 July 2018 including search terms 'fertility service', 'waiting list', 'treatment-independent' and 'spontaneous conception'. Language restrictions were not imposed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were studies (at least partly) reporting on infertile couples with female partner of age ≥35 years who attended fertility services, underwent fertility workup (e.g. history, semen analysis, tubal status and ovulation status) and were exposed to natural conception (e.g. independent of treatment such as IVF, ovulation induction and tubal surgery). Studies that exclusively studied only one infertility diagnosis, without including other women presenting to infertility services for other causes of infertility, were excluded. For studies that met the inclusion criteria, study authors were contacted to provide IPD, after which fertility outcomes for women of age ≥35 years were retrieved. Time to pregnancy or livebirth and the effect of increasing age on fertility outcomes after adjustment for other prognostic factors were analysed. Quality of studies was graded with the Newcastle-Ottawa Scale (non-randomised controlled trials (RCTs)) or the Cochrane Risk of Bias tool (for RCTs). MAIN RESULTS AND THE ROLE OF CHANCE: We included nine studies (seven cohort studies and two RCTs) (n = 4379 women of at least age 35 years), with the observed composite primary outcome of ongoing pregnancy or livebirth occurring in 429 women (9.8%) over a median follow-up of 5 months (25th to 75th percentile: 2.5-8.5 months). Studies were of moderate to high quality. The probability of natural conception significantly decreased with any diagnosis of infertility, when compared with unexplained infertility. We found non-linear effects of female age and duration of infertility on ongoing pregnancy and tabulated the predicted probabilities for unexplained infertile women aged 35-42 years with either primary or secondary infertility and with a duration of infertility from 1 to 6 years. For a 35-year-old woman with 2 years of primary unexplained infertility, the predicted probability of natural conception leading to ongoing pregnancy or livebirth was 0.15 (95% CI 0.11-0.19) after 6 months and 0.24 (95% CI 0.17-0.30) after 12 months. For a 42-year-old woman, this decreased to 0.08 (95% CI 0.04-0.11) after 6 months and 0.13 (95% CI 0.07-0.18) after 12 months. LIMITATIONS, REASONS FOR CAUTION: In the studies selected, there were different study designs, recruitment strategies in different centres, protocols and countries and different methods of assessment of infertility. Data were limited for women above the age of 40 years. WIDER IMPLICATIONS OF THE FINDINGS: Women attending fertility services should be encouraged to pursue natural conception while waiting for treatment to commence and after treatment if it is unsuccessful. Our results may aid in counselling women, and, in particular, for those with unexplained infertility. STUDY FUNDING/COMPETING INTEREST(S): S.J.C. received funding from the University of Adelaide Summer Research Scholarship. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437), B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, iGenomix and Guerbet. B.W.M. reports research support by Merck and Guerbet. PROSPERO REGISTRATION NUMBER: CRD42018096552.

Importance of the physical exam: double-blind randomized controlled trial of radiologic interpretation of ventral hernias after selective clinical information.

PURPOSE: Increasingly, radiologic imaging is obtained as part of the pathway in diagnosing ventral hernias. Often, radiologists receive incomplete or incorrect clinical information from clinicians. OBJECTIVE: The aim of the study is to determine if clinical exam findings alter radiological interpretation of ventral hernias on CT. METHODS: This is a single-institution double-blind, randomized trial. All patients with a recent abdominal/pelvic CT scan seen in various surgical clinics were enrolled. A surgeon blinded to the CT scan findings performed a standardized physical examination and assessed for the presence of a ventral hernia. Seven independent radiologists blinded to the study design reviewed the scans. Each radiologist received one of three types of clinical exam data per CT: accurate (correct), inaccurate (purposely incorrect), or none. Allocation was random and stratified by the presence of clinical hernia. The primary outcome was the proportion of radiologic hernias detected, analyzed by chi square. RESULTS: 115 patients were enrolled for a total of 805 CT scan reads. The proportion of hernias detected differed by up to 25% depending on if accurate, no, or inaccurate clinical information was provided. Inaccurate clinical data in patients with no hernia on physical exam led to a significant difference in the radiologic hernia detection rate (54.3% versus 35.7%, p = 0.007). No clinical data in patients with a hernia on physical exam led to a lower radiologic hernia detection rate (75.0% versus 93.8%, p = 0.001). CONCLUSIONS: The presence and accuracy of clinical information provided to radiologists impacts the diagnosis of abdominal wall hernias in up to 25% of cases. Standardization of both clinical and radiologic examinations for hernias and their reporting are needed. TRIAL REGISTRATION: Clinicaltrials.gov, Number NCT03121131, https://clinicaltrials.gov/ct2/show/NCT03121131.

Quantitative susceptibility mapping as an indicator of subcortical and limbic iron abnormality in Parkinson's disease with dementia.

Late stage Parkinson's disease (PD) patients were commonly observed with other non-motor comorbidities such as dementia and psychosis. While abnormal iron level in the substantia nigra was clinically accepted as a biomarker of PD, it was also suggested that the increased iron deposition could impair other brain regions and induce non-motor symptoms. A new Magnetic Resonance Imaging (MRI) called Quantitative Susceptibility Mapping (QSM) has been found to measure iron concentration in the grey matter reliably. In this study, we investigated iron level of different subcortical and limbic structures of Parkinson's disease (PD) patients with and without dementia by QSM. QSM and volumetric analysis by MRI were performed in 10 PD dementia (PDD) patients (73 ±â€¯6 years), 31 PD patients (63 ±â€¯8 years) and 27 healthy controls (62 ±â€¯7 years). No significant differences were observed in the L-Dopa equivalent dosage for the two PD groups (p = 0.125). Putative iron content was evaluated in different subcortical and limbic structures of the three groups, as well as its relationship with cognitive performance. One-way ANCOVA with FDR adjustment at level of 0.05, adjusted for age and gender, showed significant group differences for left and right hippocampus (p = 0.015 & 0.032, respectively, BH-corrected for multiple ROIs) and right thalamus (p = 0.032, BH-corrected). Post-hoc test with Bonferroni's correction suggested higher magnetic susceptibility in PDD patients than healthy controls in the left and right hippocampus (p = 0.001 & 0.047, respectively, Bonferroni's corrected), while PD patients had higher magnetic susceptibility than the healthy controls in right hippocampus and right thalamus (p = 0.006 & 0.005, respectively, Bonferroni's corrected). PDD patients also had higher susceptibility than the non-demented PD patients in left hippocampus (p = 0.046, Bonferroni's corrected). The magnetic susceptibilities of the left and right hippocampus were negatively correlated with the Mini-Mental State Examination score (r = -0.329 & -0.386, respectively; p < 0.05). This study provides support for iron accumulation in limbic structures of PDD and PD patients and its correlation with cognitive performance, however, its putative involvement in development of non-motor cognitive dysfunction in PD pathogenesis remains to be elucidated.

The impact factor of an open access journal does not contribute to an article's citations.

Background Citations of papers are positively influenced by the journal's impact factor (IF). For non-open access (non-OA) journals, this influence may be due to the fact that high-IF journals are more often purchased by libraries, and are therefore more often available to researchers, than low-IF journals. This positive influence has not, however, been shown specifically for papers published in open access (OA) journals, which are universally accessible, and do not need library purchase. It is therefore important to ascertain if the IF influences citations in OA journals too. Methods 203 randomized controlled trials (102 OA and 101 non-OA) published in January 2011 were included in the study. Five-year citations for papers published in OA journals were compared to those for non-OA journals. Source papers were derived from PubMed. Citations were retrieved from Web of Science, Scopus, and Google Scholar databases. The Thompson-Reuter's IF was used. Results OA journals were found to have significantly more citations overall compared to non-OA journals (median 15.5 vs 12, p=0.039). The IF did not correlate with citations for OA journals (Spearman's rho =0.187, p=0.60). The increase in the citations with increasing IF was minimal for OA journals (beta coefficient = 3.346, 95% CI -0.464, 7.156, p=0.084). In contrast, the IF did show moderate correlation with citations for articles published in non-OA journals (Spearman's rho=0.514, p<0.001). The increase in the number of citations was also significant (beta coefficient = 4.347, 95% CI 2.42, 6.274, p<0.001). Conclusion It is better to publish in an OA journal for more citations. It may not be worth paying high publishing fees for higher IF journals, because there is minimal gain in terms of increased number of citations. On the other hand, if one wishes to publish in a non-OA journal, it is better to choose one with a high IF.

High Temperature Terahertz Detectors Realized by a GaN High Electron Mobility Transistor.

In this work, a high temperature THz detector based on a GaN high electron mobility transistor (HEMT) with nano antenna structures was fabricated and demonstrated to be able to work up to 200 °C. The THz responsivity and noise equivalent power (NEP) of the device were characterized at 0.14 THz radiation over a wide temperature range from room temperature to 200 °C. A high responsivity Rv of 15.5 and 2.7 kV/W and a low NEP of 0.58 and 10 pW/Hz0.5 were obtained at room temperature and 200 °C, respectively. The advantages of the GaN HEMT over other types of field effect transistors for high temperature terahertz detection are discussed. The physical mechanisms responsible for the temperature dependence of the responsivity and NEP of the GaN HEMT are also analyzed thoroughly.

Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness.

OBJECTIVES: External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF). METHODS: A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness. RESULTS: The mean axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA) testing in all three groups demonstrated no significant difference (F(2,12) = 2.057, p = 0.171).There was a significant difference in mean torsional stiffness between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP (0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No catastrophic failures were observed. CONCLUSION: Using the LCP as an external fixator may provide a viable and attractive alternative to the traditional UEF as its lower profile makes it more acceptable to patients, while not compromising on axial and torsional stiffness.Cite this article: B. F. H. Ang, J. Y. Chen, A. K. S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe. Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness. Bone Joint Res 2017;6:216-223. DOI: 10.1302/2046-3758.64.2000470.

Spatial and Temporal distribution of Aedes (Diptera: Culicidae) mosquitoes in Shah Alam.

Surveys are conducted at central zone of Shah Alam in determining the distribution of dengue vector mosquito population. A minimum of 100 houses was randomly searched for breeding at every 24 localities in central zone of Shah Alam. Number of buildings at central zone of Shah Alam was obtained from the local authorities in order to calculate the sample size. The positive and wet containers in each locality were recorded and the types of container for positive containers were categorized accordingly. The numbers of larvae in each container were collected. The pupal index (PI), house index (HI), container index (CI), and the Breteau index were calculated for each locality. Plastic containers (CID 1) showed the highest number of positive, while Seksyen 1 and Seksyen 14 showed the highest percentage of BI with 70% and 80% respectively. This study would provide the information regarding Aedes mosquito infestation and , highlighted the central region as the dengue fever was fluctuating in these area. It can also help to create strategy to reduce the mosquito menace in our country with more cost-effective mosquito larval control.

Ring-opened aminothienopyridazines as novel tau aggregation inhibitors.

Aminothienopyridazines (ATPZs) have demonstrated efficacy, in vitro, as tau protein aggregation inhibitors. Modifications were made to the ATPZ scaffold to determine the importance of certain structural features for activity. More specifically, ring-opened analogues detached at the nitrogen-nitrogen bond of the pyridazine, were synthesized and their inhibitory activity evaluated. Preliminary data suggests that the ring-opened structures retain inhibitory activity, independent of tau oxidation. The structures detailed represent the beginnings of a deconstruction-reconstruction-elaboration study, with the aim of identifying simpler scaffolds, which retain activity and can be optimized in terms of physiochemical properties.

Optomechanical design and construction of a vacuum-compatible optical parametric oscillator for generation of squeezed light.

With the recent detection of gravitational waves, non-classical light sources are likely to become an essential element of future detectors engaged in gravitational wave astronomy and cosmology. Operating a squeezed light source under high vacuum has the advantages of reducing optical losses and phase noise compared to techniques where the squeezed light is introduced from outside the vacuum. This will ultimately provide enhanced sensitivity for modern interferometric gravitational wave detectors that will soon become limited by quantum noise across much of the detection bandwidth. Here we describe the optomechanical design choices and construction techniques of a near monolithic glass optical parametric oscillator that has been operated under a vacuum of 10(-6) mbar. The optical parametric oscillator described here has been shown to produce 8.6 dB of quadrature squeezed light in the audio frequency band down to 10 Hz. This performance has been maintained for periods of around an hour and the system has been under vacuum continuously for several months without a degradation of this performance.

Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality.

More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6·5 to -1·5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8·4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.

Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model.

Prenatal exposure to maternal immune activation (MIA) increases the risk of schizophrenia and autism in the offspring. The MIA rodent model provides a valuable tool to directly test the postnatal consequences of exposure to an early inflammatory insult; and examine novel preventative strategies. Here we tested the hypotheses that behavioural differences in the MIA mouse model are accompanied by in vivo and ex vivo alterations in brain biochemistry; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acid (PUFA). The viral analogue PolyI:C (POL) or saline (SAL) was administered to pregnant mice on gestation day 9. Half the resulting male offspring (POL=21; SAL=17) were weaned onto a conventional lab diet (n-6 PUFA); half were weaned onto n-3 PUFA-enriched diet. In vivo magnetic resonance spectroscopy measures were acquired prior to behavioural tests; glutamic acid decarboxylase 67 (GAD67) and tyrosine hydroxylase protein levels were measured ex vivo. The main findings were: (i) Adult MIA-exposed mice fed a standard diet had greater N-acetylaspartate/creatine (Cr) and lower myo-inositol/Cr levels in the cingulate cortex in vivo. (ii) The extent of these metabolite differences was correlated with impairment in prepulse inhibition. (iii) MIA-exposed mice on the control diet also had higher levels of anxiety and altered levels of GAD67 ex vivo. (iv) An n-3 PUFA diet prevented all the in vivo and ex vivo effects of MIA observed. Thus, n-3 PUFA dietary enrichment from early life may offer a relatively safe and non-toxic approach to limit the otherwise persistent behavioural and biochemical consequences of prenatal exposure to inflammation. This result may have translational importance.