Cyanobacteria blooms cannot be controlled by effective microorganisms (EM) from mud- or Bokashi-balls

In controlled experiments, the ability of ‘‘Effective Microorganisms (EM, in the form of mudballs or Bokashi-balls)’’ was tested for clearing waters from cyanobacteria. We found suspensions of EM-mudballs up to 1 g l-1 to be ineffective in reducing cyanobacterial growth. In all controls and EM-mudball treatments up to 1 g l-1 the cyanobacterial chlorophyll-a (Chl-a) concentrations increased within 4 weeks from&120 to 325–435 lg l-1. When pieces of EM-mudballs (42.5 g) were added to 25-l lake water with cyanobacteria, no decrease of cyanobacteria as compared to untreated controls was observed. In contrast, after 4 weeks cyanobacterial Chl-a concentrations were significantly higher in EM-mudball treatments (52 lg l-1) than in controls (20 lg l-1). Only when suspensions with extremely high EM-mudball concentrations were applied (i.e., 5 and 10 g l-1), exceeding the recommended concentrations by orders of magnitude, cyanobacterial growth was inhibited and a bloom forming concentration was reduced strongly. In these high dosing treatments, the oxygen concentration dropped initially to very low levels of 1.8 g l-1. This was most probably through forcing strong light limitation on the cyanobacteria caused by the high amount of clay and subsequent high turbidity of the water. Hence, this study yields no support for the hypothesis that EM is effective in preventing cyanobacterial proliferation or in terminating blooms. We consider EM products to be ineffective because they neither permanently bind nor remove phosphorus from eutroficated systems, they have no inhibiting effect on cyanobacteria, and they could even be an extra source of nutrients

Optimal Alignment of Structures for Finite and Periodic Systems

Finding the optimal alignment between two structures is important for identifying the minimum root-mean-square distance (RMSD) between them and as a starting point for calculating pathways. Most current algorithms for aligning structures are stochastic, scale exponentially with the size of structure, and the performance can be unreliable. We present two complementary methods for aligning structures corresponding to isolated clusters of atoms and to condensed matter described by a periodic cubic supercell. The first method (Go-PERMDIST), a branch and bound algorithm, locates the global minimum RMSD deterministically in polynomial time. The run time increases for larger RMSDs. The second method (FASTOVERLAP) is a heuristic algorithm that aligns structures by finding the global maximum kernel correlation between them using fast Fourier transforms (FFTs) and fast SO(3) transforms (SOFTs). For periodic systems, FASTOVERLAP scales with the square of the number of identical atoms in the system, reliably finds the best alignment between structures that are not too distant, and shows significantly better performance than existing algorithms. The expected run time for Go-PERMDIST is longer than FASTOVERLAP for periodic systems. For finite clusters, the FASTOVERLAP algorithm is competitive with existing algorithms. The expected run time for Go-PERMDIST to find the global RMSD between two structures deterministically is generally longer than for existing stochastic algorithms. However, with an earlier exit condition, Go-PERMDIST exhibits similar or better performance.This work was supported by the EPSRC Cambridge NanoDTC, EP/G037221/1

The COVID-19 Psychological Distress Scale (CPDS-16): development and initial validation

The outbreak of COVID-19 has caused psychological distress among the Indian population. There are several scales that assess fear and distress related to COVID-19 among individuals. However, these scales are context-specific and lack multi-cultural environment applicability in countries such as India. Therefore, the present study developed a psychometric instrument to assess psychological responses to COVID-19 among the Indian population. A total of 420 participants (60.5% females, Mage=25.89 years) were recruited online using a convenience sampling technique. The 16-item COVID-19 Psychological Distress Scale (CPDS-16) was developed based on the extensive review of the existing scales on psychological constructs related to COVID-19 (yielding four scales with a total of 37 items) and independent review by two external experts. Internal consistency and reliability of the scale was established by using corrected item-total correlations, Cronbach's alpha, and McDonald's omega. Factor structure of the scale was determined by using exploratory factor analysis (EFA). Convergent validity of the scale was established by correlating CPDS-16 scores with the three subscales of the Depression, Anxiety, and Stress Scale (DASS-21). Corrected item-total correlations (range = 0.43 to 0.70), Cronbach's alpha (α = 0.90), and McDonald's omega (ω = 0.89) provided evidence for very good internal consistency and reliability of the scale. EFA of the CPDS-16 demonstrated a two-factor structure identified as 'individual level distress' (10 items) and 'community level distress' (6 items). Convergent validity of the scale was established using the DASS-21 with statistically significant and positive correlations between CPDS-16 and the three DASS-21 subscales (i.e., depression, anxiety, and stress). The CPDS-16 is a reliable and valid instrument in assessing psychological distress caused due to COVID-19 with robust psychometric properties. The scale can be administered rapidly and is useful in screening psychological distress caused due to COVID-19

Structure and stability of symptoms in first episode psychosis: a longitudinal network approach

Early psychosis is characterised by heterogeneity in illness trajectories, where outcomes remain poor for many. Understanding psychosis symptoms and their relation to illness outcomes, from a novel network perspective, may help to delineate psychopathology within early psychosis and identify pivotal targets for intervention. Using network modelling in first episode psychosis (FEP), this study aimed to identify: (a) key central and bridge symptoms most influential in symptom networks, and (b) examine the structure and stability of the networks at baseline and 12-month follow-up. Data on 1027 participants with FEP were taken from the National EDEN longitudinal study and used to create regularised partial correlation networks using the ‘EBICglasso’ algorithm for positive, negative, and depressive symptoms at baseline and at 12-months. Centrality and bridge estimations were computed using a permutation-based network comparison test. Depression featured as a central symptom in both the baseline and 12-month networks. Conceptual disorganisation, stereotyped thinking, along with hallucinations and suspiciousness featured as key bridge symptoms across the networks. The network comparison test revealed that the strength and bridge centralities did not differ significantly between the two networks (C = 0.096153; p = 0.22297). However, the network structure and connectedness differed significantly from baseline to follow-up (M = 0.16405, p = <0.0001; S = 0.74536, p = 0.02), with several associations between psychosis and depressive items differing significantly by 12 months. Depressive symptoms, in addition to symptoms of thought disturbance (e.g. conceptual disorganisation and stereotyped thinking), may be examples of important, under-recognized treatment targets in early psychosis, which may have the potential to lead to global symptom improvements and better recovery

Exploring professionals' understanding, interpretation and implementation of the 'appropriate medical treatment test' in the 2007 amendment of the Mental Health Act 1983.

BACKGROUND: The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available. AIMS: As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice. METHOD: Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process. RESULTS: We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice. CONCLUSIONS: Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter

We address the open question of performing an explicit stabilisation of all closed string moduli (including dilaton, complex structure and Kaehler moduli) in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric geometry we construct Calabi-Yau manifolds with del Pezzo singularities. D-branes located at such singularities can support the Standard Model gauge group and matter content. In order to control complex structure moduli stabilisation we consider Calabi-Yau manifolds which exhibit a discrete symmetry that reduces the effective number of complex structure moduli. We calculate the corresponding periods in the symplectic basis of invariant three-cycles and find explicit flux vacua for concrete examples. We compute the values of the flux superpotential and the string coupling at these vacua. Starting from these explicit complex structure solutions, we obtain AdS and dS minima where the Kaehler moduli are stabilised by a mixture of D-terms, non-perturbative and perturbative alpha'-corrections as in the LARGE Volume Scenario. In the considered example the visible sector lives at a dP_6 singularity which can be higgsed to the phenomenologically interesting class of models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde

Molecular diversity and distribution of eastern Atlantic and Mediterranean dogfishes Squalus highlight taxonomic issues in the genus

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The alpha taxonomy of the globally distributed shark genus Squalus has been under intense investigation recently, and many new species have been described over the last decade. However, taxonomic uncertainty remains about several taxa. Without consistent nomenclature and the ability to reliably distinguish between the different Squalus species, basic data collection, downstream conservation and management efforts are seriously compromised. To aid in clarifying the taxonomic status of Squalus species in the eastern Atlantic and Mediterranean, we assessed species diversity at the molecular level and evaluated the consistency in species identification in the region. Samples from all nominal Squalus species recognized in the above regions were collected in an international effort and sequenced for regions of the mitochondrial COI and ND2 genes. These data were further analysed alongside publicly available sequences, including 19 of the 26 Squalus species globally recognized, to compare the regional genus-level diversity with that found elsewhere. Our results confirm inconsistent species identification in the eastern Atlantic and Mediterranean Squalus, particularly concerning S. blainville and S. megalops, and reinforce the need to revise the status of S. megalops and S. mitsukurii as they may include several distinct species distributed around the world. The status of S. blainville is also discussed in the light of the current findings and its problematic taxonomic history.Systematic Research Fund. Fundação para a Ciência e Tecnologia. Grant Number: SFRH/BPD/77487/2007. Social European Fund. Portuguese funds. New Zealand National Institute of Water and Atmospheric Research Lt

Prevalence of treatment resistance and clozapine use in early intervention services

BACKGROUND: Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics. AIMS: This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services. METHOD: Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points. RESULTS: A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine. CONCLUSIONS: Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period

The generalised anxiety stigma scale (GASS): psychometric properties in a community sample

<p>Abstract</p> <p>Background</p> <p>Although there is substantial concern about negative attitudes to mental illness, little is known about the stigma associated with Generalised Anxiety Disorder (GAD) or its measurement. The aim of this study was to develop a multi-item measure of Generalised Anxiety Disorder stigma (the GASS).</p> <p>Methods</p> <p>Stigma items were developed from a thematic analysis of web-based text about the stigma associated with GAD. Six hundred and seventeen members of the public completed a survey comprising the resulting 20 stigma items and measures designed to evaluate construct validity. Follow-up data were collected for a subset of the participants (n = 212).</p> <p>Results</p> <p>The factor structure comprised two components: Personal Stigma (views about Generalised Anxiety Disorder); and Perceived Stigma (views about the beliefs of most others in the community). There was evidence of good construct validity and reliability for each of the Generalised Anxiety Stigma Scale (GASS) subscales.</p> <p>Conclusions</p> <p>The GASS is a promising brief measure of the stigma associated with Generalised Anxiety Disorder.</p

A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301)

\ua9 The Author(s) 2024.Purpose: 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU. Patients and methods: NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity. Results: Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0–11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in &lt; 10% of patients. NUC-3373 showed a favorable PK profile, with dose-proportionality and a prolonged half-life compared to 5-FU. A best overall response of stable disease was observed, with prolonged progression-free survival. Conclusion: NUC-3373 was well-tolerated in a heavily pre-treated solid tumor patient population, including those who had relapsed on prior 5-FU. The MTD and RP2D was defined as 2500 mg/m2 NUC-3373 weekly. NUC-3373 is currently in combination treatment studies. Trial registration: Clinicaltrials.gov registry number NCT02723240. Trial registered on 8th December 2015. https://clinicaltrials.gov/study/NCT02723240