Reanalysis of the ß-ν[over ¯]_{e} Angular Correlation Measurement from the aSPECT Experiment with New Constraints on Fierz Interference.

On the basis of revisions of some of the systematic errors, we reanalyzed the electron-antineutrino angular correlation (a coefficient) in free neutron decay inferred from the recoil energy spectrum of the protons which are detected in 4π by the aSPECT spectrometer. With a=-0.104 02(82) the new value differs only marginally from the one published in 2020. The experiment also has sensitivity to b, the Fierz interference term. From a correlated (b,a) fit to the proton recoil spectrum, we derive a limit of b=-0.0098(193) which translates into a somewhat improved 90% confidence interval region of -0.041≤b≤0.022 on this hypothetical term. Tighter constraints on b can be set from a combined [shown as superscript (c)] analysis of the PERKEO III (ß asymmetry) and aSPECT measurement which suggests a finite value of b with b^{(c)}=-0.0181±0.0065 deviating by 2.82σ from the standard model.

Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

Neuromodulation and Eating Disorders.

PURPOSE OF REVIEW: We review recent evidence on the use of neuromodulation for treating eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. We evaluate studies on (a) modern non-invasive methods of brain stimulation, such as transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), (b) electroconvulsive therapy (ECT) and (c) more invasive techniques, including deep brain stimulation (DBS). RECENT FINDINGS: Most reports on the clinical applications of neuromodulation in EDs are limited to case studies, case series and small clinical trials. The majority have focused on severe, enduring and hard-to-treat cases of AN. In this population, data suggest that both rTMS and DBS have therapeutic potential and are safe and acceptable. High-quality clinical trials in different ED populations are needed which investigate different stimulation methods, sites and parameters, the use of neuromodulation as stand-alone and/or adjunctive treatment, as well as the mechanisms of action.

[Gene-based treatment in spinal muscular atrophy]. / Genetisch basierte Therapien bei spinaler Muskelatrophie.

BACKGROUND: The 5q-associated spinal muscular atrophy (SMA) affects ~ 80-120 newborns annually. The disease is characterized by progressive paresis involving the bulbar and respiratory musculatures. The phenotypes are very heterogeneous ranging from severe courses with early death in the first years of life to loss of gait in older age. OBJECTIVE: There are now an increasing number of causally targeted therapies available that can either directly interfere with the transcription of the gene causing the disease or replace the homozygous loss of the SMN1 gene. This work aims to elucidate the current state of therapy in different groups of patients with SMA. MATERIAL AND METHODS: Presentation of clinical trials and basic studies with a focus on patients with disease onset in adulthood. RESULTS: The clinical studies all show improvement or stabilization of motor function; however, in individual cases, the burden of the therapy for severely immobilized patients must be considered in addition to the efficacy in the treatment decision. Even if the drugs show a good safety profile, observations on the long-term efficacy and safety of the new substance classes are still lacking. CONCLUSION: The study landscape shows a good efficacy of the currently approved therapies across all degrees of severity and age groups. Due to the lack of comparative studies, the decision on the appropriate therapy should therefore be made according to an individual risk-benefit assessment.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Confocal Raman microscopy in life sciences.

Microscopy techniques are widely used in life sciences to study cells and tissues. Fluorescence microscopy, for example, is a very common method in many laboratories. While reliable and strong fluorescence signals are a clear advantage of this method, the labelling procedure with fluorescent dyes, the availability of required antibodies or the potentially necessary genetic modifications of the studied organism all introduce potential complications. By contrast, confocal Raman microscopy is a label-free and non-destructive imaging technique. In contrast to infrared microscopy, it is easily applicable in aqueous environments. Different microscope setups and combinations allow for the examination of various solid and liquid samples, even in their typical environments. The article demonstrates the analyzing capability of confocal Raman microscopy and correlative techniques through application examples of eukaryotic and prokaryotic cells, and cancerous and normal tissues and shows how confocal Raman microscopy provides valuable information for a more comprehensive understanding of the investigated sample.

Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study.

OBJECTIVE: To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. RESULTS: Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI): -0.33, 0.76]; 400 U: 0.42 [95% CI: -0.26, 1.10]; 200 U: -0.03 [95% CI: -0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. CONCLUSIONS: There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. GOV IDENTIFIER: NCT02230956.

Advances in the treatment of anorexia nervosa: a review of established and emerging interventions.

BACKGROUND: Anorexia nervosa (AN) is a disabling, deadly and costly mental disorder. Until recently, treatment recommendations were based on expert opinion and limited evidence. The aim of this systematic review is to synthesise recent evidence on established and emerging AN treatments and to forecast trends for future developments. METHODS: We systematically review trials of established treatments and associated process outcome studies from the last 5 years, published since a previous review in this journal. 'Established' treatments were those that are widely used in AN, recommended by guidelines and/or have been tested in at least one large randomised controlled trial. Secondly, we summarise emerging treatments for AN, i.e. those that have only been (or are currently being) tested in proof-of concept, feasibility or pilot trials. RESULTS: We identified 19 published trials of established treatments (15 of high or moderate quality), mostly assessing psychological therapies (n = 17). We also found 11 published trials of emerging treatments, and a total of 34 registered, as yet unpublished trials. Promising emerging treatments include cognitive remediation therapy, exposure therapy and non-invasive neuromodulation. CONCLUSIONS: Evidence generation on the treatment of AN has dramatically accelerated, with our understanding of the role of family-based approaches for adolescents more nuanced and a range of psychological approaches available for the treatment of adults. Evidence on emerging treatments and from forthcoming trials suggests that there is a shift towards more targeted brain-based interventions. Future studies need to focus on elucidating mechanisms of action of treatments and what works best for whom.

A multimodal microcharacterisation of trace-element zonation and crystallographic orientation in natural cassiterite by combining cathodoluminescence, EBSD, EPMA and contribution of confocal Raman-in-SEM imaging.

In cassiterite, tin is associated with metals (titanium, niobium, tantalum, indium, tungsten, iron, manganese, mercury). Knowledge of mineral chemistry and trace-element distribution is essential for: the understanding of ore formation, the exploration phase, the feasibility of ore treatment, and disposal/treatment of tailings after the exploitation phase. However, the availability of analytical methods make these characterisations difficult. We present a multitechnical approach to chemical and structural data that includes scanning electron microscopy (SEM)-based imaging and microanalysis techniques such as: secondary and backscattered electrons, cathodoluminescence (CL), electron probe microanalyser (EPMA), electron backscattered diffraction (EBSD) and confocal Raman-imaging integrated in a SEM (RISE). The presented results show the complementarity of the used analytical techniques. SEM, CL, EBSD, EPMA provide information from the interaction of an electron beam with minerals, leading to atomistic information about their composition, whereas RISE, Raman spectroscopy and imaging completes the studies with information about molecular vibrations, which are sensitive to structural modifications of the minerals. The correlation of Raman bands with the presence/absence of Nb, Ta, Fe (heterovalent substitution) and Ti (homovalent substitution) is established at a submicrometric scale. Combination of the different techniques makes it possible to establish a direct link between chemical and crystallographic data of cassiterite.

Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans. METHODS: To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST). RESULTS: Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects. CONCLUSIONS: This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the generalizability of our findings. Future studies have to explore the gender dependency and the tolerability of the oxytocin-mediated increase in heart rate. This randomized controlled trial was retrospectively registered at the German Trials Register (DRKS00009399) on the 02 October 2015.

A randomised controlled trial of three psychological treatments for anorexia nervosa.

BACKGROUND: There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy. METHOD: A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25-40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment. RESULTS: Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up. CONCLUSION: The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN 12611000725965) http://www.anzctr.org.au/.

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Determination of physical emulsion stabilization mechanisms of wood hemicelluloses via rheological and interfacial characterization.

Materials manufacturing industries seek efficient, economic, and sustainable compounds for stabilizing dispersed systems such as emulsions. In this study, novel, abundant biobased hydrocolloids spruce galactoglucomannans (GGM) and birch glucuronoxylans (GX) were obtained from a forestry biorefining process and characterized as versatile stabilizers of rapeseed oil-in-water emulsions. For the first time, GGM and GX isolated by pressurized hot water extraction (PHWE) of spruce and birch saw meal, respectively, were studied in emulsions. The PHWE wood hemicelluloses-polysaccharides with relatively low molar mass-facilitated the formation of emulsions with small average droplet size and efficiently prevented droplet coalescence. GGM and GX lowered the surface tension of emulsions' oil-water interface and increased the viscosity of the continuous phase. However, viscosity of the wood hemicellulose-based systems was low compared to that of commercial polymeric stabilizers. GGM-stabilized emulsions with varying oil volume fractions were characterized in terms of their rheological properties, including large amplitude oscillation shear (LAOS) measurements, and compared to emulsions prepared with a classical small-molecular surfactant, Tween20. The physical emulsion stabilization mechanisms of GGM and GX are suggested as steric repulsion assisted by Pickering-type stabilization. Wood hemicelluloses have potential as highly promising future bioproducts for versatile industrial applications involving colloidal systems and soft materials.

[Mortui vivos docent : The dead teach the living]. / Mortui vivos docent : Die Toten lehren die Lebenden.

There are considerable similarities and intersections between forensic medicine and emergency medicine. This applies especially to frustraneously resuscitated patients or other lethal clinical courses of traumatized patients who are subject to latter forensic autopsy. Cooperation between departments of emergency and forensic medicine not only has emergency medical training potential, but also the possibility of retrospective evaluation of medical emergency measures - both in individual cases and with regard to epidemiological aspects. In particular, the widespread registration of autopsied pre-hospital trauma deaths that occurred despite on-scene resuscitation attempts is useful. The pre-hospital situation represents a hotspot, but also a blind spot in the overall trauma mortality. In recent clinical registers, preclinical deaths go mostly unrecorded, despite the undisputed benefits of clinical registers.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

New limit on Lorentz-invariance- and CPT-violating neutron spin interactions using a free-spin-precession He3-Xe129 comagnetometer.

We report on the search for a CPT- and Lorentz-invariance-violating coupling of the He3 and Xe129 nuclear spins (each largely determined by a valence neutron) to posited background tensor fields that permeate the Universe. Our experimental approach is to measure the free precession of nuclear spin polarized He3 and Xe129 atoms in a homogeneous magnetic guiding field of about 400 nT using LTC SQUIDs as low-noise magnetic flux detectors. As the laboratory reference frame rotates with respect to distant stars, we look for a sidereal modulation of the Larmor frequencies of the colocated spin samples. As a result we obtain an upper limit on the equatorial component of the background field interacting with the spin of the bound neutron b(⊥)(n)<8.4 × 10(-34) GeV (68% C.L.). Our result improves our previous limit (data measured in 2009) by a factor of 30 and the world's best limit by a factor of 4.

Gravity resonance spectroscopy constrains dark energy and dark matter scenarios.

We report on precision resonance spectroscopy measurements of quantum states of ultracold neutrons confined above the surface of a horizontal mirror by the gravity potential of Earth. Resonant transitions between several of the lowest quantum states are observed for the first time. These measurements demonstrate that Newton's inverse square law of gravity is understood at micron distances on an energy scale of 10-14 eV. At this level of precision, we are able to provide constraints on any possible gravitylike interaction. In particular, a dark energy chameleon field is excluded for values of the coupling constant ß>5.8×108 at 95% confidence level (C.L.), and an attractive (repulsive) dark matter axionlike spin-mass coupling is excluded for the coupling strength gsgp>3.7×10-16 (5.3×10-16) at a Yukawa length of λ=20 µm (95% C.L.).

An Internet-based program to enhance motivation to change in females with symptoms of an eating disorder: a randomized controlled trial.

BACKGROUND: Previous research has demonstrated an association between low motivation to change and an unfavorable treatment outcome in patients with an eating disorder. Consequently, various studies have examined the effects of motivational enhancement therapy (MET) on motivation to change and treatment outcome in eating disorders. In each of these studies, MET was administered in a face-to-face setting. However, because of its anonymity and ease of access, the internet provides several advantages as the format for such an intervention. Therefore, the current study investigated the effects of an internet-based program ('ESS-KIMO') to enhance motivation to change in eating disorders. METHOD: In total, 212 females were accepted for participation and assigned randomly to the intervention condition (n = 103) or waiting-list control condition (n = 109). The intervention consisted of six online MET sessions. Before and after the intervention or waiting period respectively, participants completed the Eating Disorder Examination Questionnaire (EDE-Q), the Stages of Change Questionnaire for Eating Disorders (SOCQ-ED), the Pros and Cons of Eating Disorders Scale (P-CED), the Self-Efficacy Scale (SES), and the Rosenberg Self-Esteem Scale (RSES). A total of 125 participants completed the assessment post-treatment. Completer analyses and intent-to-treat analyses were performed. RESULTS: Significant time × group interactions were found, indicating a stronger increase in motivational aspects and self-esteem, in addition to a stronger symptom reduction on some measures from pre- to post-treatment in the intervention group compared to the control group. CONCLUSIONS: Internet-based approaches can be considered as useful for enhancing motivation to change in eating disorders and for yielding initial symptomatic improvement.

Modular real-time PCR screening assay for common European animal families.

A screening assay based on real-time PCR and melt curve analysis was developed to detect DNA from nine common European animal families/species and human. The assay consists of a 10-cycle universal pre-amplification followed by specific nested PCR and was designed to exploit the different melting temperatures (T m) of family/species-specific 12S ribosomal ribonucleic acid and cytochrome b fragments, which are amplified in duplex reactions. Case-related modular application is possible. Beyond determination of the animal family and discrimination from human DNA, evaluation of the melt curve in some cases additionally allows for species determination (e.g. cat vs. lynx). The method presents a quick, flexible and sample-saving approach to assess non-human DNA at low expenses, and it is especially useful in resolution of DNA mixtures.