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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.
There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive Ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
This was a 12 week rater blind placebo controlled study. All to gather 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using PANSS, CGI, GAF and AIMS.
Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual (TAU) on PANSS total score, although, this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Anti-inflammatory treatments have shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. This study has led to a larger SMRI-funded, double blind, randomized control trial.
Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antagonist that has limited effects on cytokine production. This presentation will address their efficacy and mechanism of action.
1) Update on trials with minocycline including our own positive finding on negative symptoms (PMID: 16959472)
2) Present new results with ondansetron and simvastatin summarised below.
Ondansetron (8mg) and simvastatin (40mg) vs placebos in 2x2 design (PMID: 23782463). Patients aged 18-65, stable treatment, DSM IV schizophrenia-related diagnosis. PANSS and cognition at 0,3,6 months.
The four cells of the 2x2 design contained 302 patients. The interaction between ondansetron and simvastatin was significant at p=.006 reflecting the lower scores in the 3 active treatment groups than in the P+P group. Ondansetron improved verbal (p=.007) and visual list learning (p=.02) with no other treatment effects on cognition.
Minocycline appears to benefit negative symptoms in early psychosis with a minor effect on cognition. Simvastatin had limited effects in our patients with established schizophrenia but its anti-inflammatory effects could be worth investigating in early psychosis. Ondansetron has a significant effect on new learning, which might be expected from its 5-HT3 antagonist properties. This may underlie a benefit on negative symptoms reported by others and us.
There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene–environment correlation.
The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0–17 years; ALSPAC) and at age 8 years (MoBa).
Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure.
Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment.
The aim of this retrospective review was to assess the overall burden and trend in spinal tuberculosis (TB) at tertiary hospitals in the Western Cape Province of South Africa. All spinal TB cases seen at the province's three tertiary hospitals between 2012 and 2015 were identified and clinical records of each case assessed. Cases were subsequently classified as bacteriologically confirmed or clinically diagnosed and reported with accompanying clinical and demographic information. Odds ratios (OR) for severe spinal disease and corrective surgery in child vs. adult cases were calculated. A total of 393 cases were identified (319 adults, 74 children), of which 283 (72%) were bacteriologically confirmed. Adult cases decreased year-on-year (P = 0.04), however there was no clear trend in child cases. Kyphosis was present in 60/74 (81%) children and 243/315 (77%) adults with available imaging. Corrective spinal surgery was performed in 35/74 (47%) children and 80/319 (25%) adults (OR 2.7, 95% confidence interval 1.6–4.5, P = 0.0003). These findings suggest that Western Cape tertiary hospitals have experienced a substantial burden of spinal TB cases in recent years with a high proportion of severe presentation, particularly among children. Spinal TB remains a public health concern with increased vigilance required for earlier diagnosis, especially of child cases.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
The effects of shape and thickness of a tin surface layer and of the energy of a 170 ps neodymium:yttrium-aluminum-garnet laser pulse on the conversion efficiency (CE) into extreme ultraviolet emission in the 13.5 nm region is investigated. Whereas a CE of up to 1.16% into the 2% reflection band of multilayer Mo/Si optics was measured for a bulk Sn target at a laser energy of 25 mJ, significant CE enhancement up to 1.49% is demonstrated for a 200-nm-thick Sn layer on a microstructured porous alumina substrate.
To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source.
A 629-bed, tertiary-care, pediatric hospital in Houston, Texas.
Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units.
We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory.
Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2–148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation.
Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer.
Epidemiological studies have established an association between obesity, insulin resistance, type 2 diabetes and a number of cancer types. Research has focused predominantly on altered endocrine factors, growth factors and signalling pathways, with little known in man about the immune involvement in the relevant pathophysiological processes. Moreover, in an era of exciting new breakthroughs in cancer immunotherapy, there is also a need to study the safety and efficacy of immunotherapeutics in the complex setting of inflammatory-driven obesity-associated cancer. This review addresses key immune cell subsets underpinning obesity-associated inflammation and describes how such immune compartments might be targeted to prevent and treat obesity-associated cancer. We propose that the modulation, metabolism, migration and abundance of pro- and anti-inflammatory cells and tumour-specific T cells might be therapeutically altered to both restore immune balance, alleviating pathological inflammation, and to improve anti-tumour immune responses in obesity-associated cancer.
With prevention and treatment of mental disorders a challenge for primary care and increasing capability of electronic medical records (EMRs) to facilitate research in practice, we aim to determine the prevalence and treatment of mental disorders by using routinely collected clinical data contained in EMRs.
We reviewed EMRs of patients randomly sampled from seven general practices, by piloting a study instrument and extracting data on mental disorders and their treatment.
Data were collected on 690 patients (age range 18–95, 52% male, 52% GMS-eligible). A mental disorder (most commonly anxiety/stress, depression and problem alcohol use) was recorded in the clinical records of 139 (20%) during the 2-year study period. While most patients with the common disorders had been prescribed medication (i.e. antidepressants or benzodiazepines), a minority had been referred to other agencies or received psychological interventions. ‘Free text’ consultation notes and ‘prescriptions’ were how most patients with disorders were identified. Diagnostic coding alone would have failed to identify 92% of patients with a disorder.
Although mental disorders are common in general practice, this study suggests their formal diagnosis, disease coding and access to psychological treatments are priorities for future research efforts.
Decompression of the endolymphatic sac for Ménière's disease gives unpredictable results. This may be because the sac is difficult to identify and decompress accurately without causing surgical trauma.
In order to test this idea, transmastoid decompression was simulated in 5 cadaver half heads and the anatomy of the endolymphatic sac was reviewed in a further 14 specimens.
The endolymphatic sac was found and confirmed by histology in all five simulated decompressions. A newly described feature, a trapezoid thickening of dura, was a useful guide. The review showed that the sac was constant proximally, but variable distally. The posterior semicircular canal, posterior fossa dura and sigmoid sinus are at risk during dissection.
The endolymphatic sac may be identified on inspection by an overlying patch of dura, thereby reducing exploratory dissection. It is best to decompress the sac as far proximally as possible, whilst protecting the posterior semicircular canal.
The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009–August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.
It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations.
To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence.
Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study).
Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA.
A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.
EMU is a wide-field radio continuum survey planned for the new Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The primary goal of EMU is to make a deep (rms ∼ 10 μJy/beam) radio continuum survey of the entire Southern sky at 1.3 GHz, extending as far North as +30° declination, with a resolution of 10 arcsec. EMU is expected to detect and catalogue about 70 million galaxies, including typical star-forming galaxies up to z ∼ 1, powerful starbursts to even greater redshifts, and active galactic nuclei to the edge of the visible Universe. It will undoubtedly discover new classes of object. This paper defines the science goals and parameters of the survey, and describes the development of techniques necessary to maximise the science return from EMU.