Effects of transcranial direct current stimulation in children and young people with psychiatric disorders: a systematic review.

Transcranial direct current stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to December 2022. Eligible studies involved multiple session (i.e., treatment) tDCS in CYP (≤ 25 years old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Of 33 eligible studies (participant N = 517), the majority (n = 27) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 13) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well tolerated with minimal side effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 79.7; range 15-172) than published studies. Although encouraging, the evidence to date is insufficient to firmly conclude that tDCS can improve clinical symptoms, mood, or cognition in CYP with psychiatric disorders. Ongoing studies appear of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e., treatment regimens). [Abstract copyright: © 2023. The Author(s).

Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial

Background: Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3–5 years in primary care patients with treatment-resistant depression. Methods: CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18–75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3–5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0–63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs). This study is registered with isrctn.com, number ISRCTN38231611. Findings: Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5–51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means −4·7 [95% CI −6·4 to −3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000. Interpretation: CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective

Oviposition by European Corn Borer (Lepidoptera: Crambidae) in Response to Various Transgenic Corn Events

Oviposition preference by European corn borers, Ostrinia nubilalis (Hubner), for or against transgenic corn would influence amounts of refuge required for resistance management. The objective of this research was to determine if various Bacillus thuringiensis (Bt) corn transgenic events influence 0. nubilalis oviposition. All commercially available events (currently 5) were evaluated, plus 1 experimental event. Results from 3 independent studies are reported, including 3 field-cage experiments with vegetative corn, 2 field-cage experiments with reproductive corn, and 2 field experiments with natural 0. nubilalis on reproductive corn. In each case, Bt corn hybrids are compared with their near isogenic hybrids by counting numbers of egg masses on each plant type. More extensive comparisons were made in 3 of the experiments by determining the number, size, and location of egg masses on the corn hybrids. Moths laid more egg masses on Bt corn than on non-Bt corn in 1 cage experiment. These results, however, were not found in any of the other experiments. There is evidence that suggests cage effects influence moth oviposition more than Bt protein. Four of the 5 cage experiments and 2 field experiments indicate that the tested Bt events do not influence 0. nubilalis oviposition. Larval injury to isogenic corn during the vegetative stage did not influence adult oviposition during the corn reproductive stage when compared with Bt corn and noninjured isogenic corn. Based on these experiments, suggestions are made for future studies that use natural 0. nubilalis rather than 0. nubilalis in cages

Effectiveness and safety of misoprostol distributed to antenatal women to prevent postpartum haemorrhage after child-births: a stepped-wedge cluster-randomized trial.

BACKGROUND: Oral misoprostol, administered by trained health-workers is effective and safe for preventing postpartum haemorrhage (PPH). There is interest in expanding administration of misoprostol by non-health workers, including task-shifting to pregnant women themselves. However, the use of misoprostol for preventing PPH in home-births remains controversial, due to the limited evidence to support self-administration or leaving it in the hands of non-health workers. This study aimed to determine if antenatally distributing misoprostol to pregnant women to self-administer at home birth reduces PPH. METHODS: Between February 2013 and March 2014, we conducted a stepped-wedge cluster-randomized trial in six health facilities in Central Uganda. Women at 28+ weeks of gestation attending antenatal care were eligible. Women in the control-arm received the standard-of-care; while the intervention-arm were offered 600 mcg of misoprostol to swallow immediately after birth of baby, when oxytocin was not available. The primary outcome (PPH) was a drop in postpartum maternal haemoglobin (Hb) by ≥ 2 g/dl, lower than the prenatal Hb. Analysis was by intention-to-treat at the cluster level and we used a paired t-tests to assess whether the mean difference between the control and intervention groups was statistically significant. RESULTS: 97% (2466/2545) of eligible women consented to participate; 1430 and 1036 in the control and intervention arms respectively. Two thousand fifty-seven of the participants were successfully followed up and 271 (13.2%) delivered outside a health facility. There was no significant difference between the study group in number of women who received a uterotonic at birth (control 80.4% vs intervention 91.4%, mean difference = -11.0%, 95% confidence interval [CI] -25.7% to 3.6%, p = 0.11). No woman took misoprostol before their baby's birth. Shivering and fever were 14.9% in the control arm compared to 22.2% in the intervention arm (mean difference = -7.2%, 95% CI -11.1% to -3.7%), p = 0.005). There was a slight, but non-significant, reduction in the percentage of women with Hb drop ≥ 2g/dl from 18.5% in the control arm to 11.4% in the intervention arm (mean difference = 7.1%, 95% CI -3.1% to 17.3%, p = 0.14). Similarly, there was no significant difference between the groups in the primary outcome in the women who delivered at home (control 9.6% vs intervention 14.5%, mean difference -4.9; 95% CI -12.7 to 2.9), p = 0.17). CONCLUSION: This study was unable to detect a significant reduction in PPH following the antenatal distribution of misoprostol. The study was registered with Pan-African Clinical Trials Network ( PACTR201303000459148, on 19/11/2012)

Determining Cloud Thermodynamic Phase from Micropulse Lidar Network Data

Determining cloud thermodynamic phase is a critical factor in studies of Earth's radiation budget. Here we use observations from the NASA Micro Pulse Lidar Network (MPLNET) and thermodynamic profiles from the Goddard Earth Observing System, version 5 (GEOS-5) to distinguish liquid water, mixed-phase, and ice water clouds. The MPLNET provides sparse global, autonomous, and continuous measurements of clouds and aerosols which have been used in a number of scientific investigations to date. The use of a standardized instrument and a common suite of data processing algorithms with thorough uncertainty characterization allows for straightforward comparisons between sites. Lidars with polarization capabilities have recently been incorporated into the MPLNET project which allows, for the first time, the ability to infer a cloud thermodynamic phase. This presentation will look specifically at the occurrence of ice and mixed phase clouds in the temperature region of -10 C to -40 C for different climatological regions and seasons. We compare MPLNET occurrences of mixed-phase clouds to an historical climatology based on observations from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) instrument aboard the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) spacecraft

The NASA Micro Pulse Lidar Network (MPLNET): Introduction of the New Version 3 Release

The NASA Micro-Pulse Lidar Network (MPLNET) is a global federated network of polarized Micro-Pulse Lidar (MPL) systems running continuously. MPLNET began in 2000, and there have been over 70 sites deployed worldwide, with 24 sites currently active and a few more planned over the next year. Seven of the long-term sites have 10+ years of data, and many more have 5+ years. Most sites are co-located with AERONET providing joint data on column and vertically resolved aerosol and cloud information. This presentation will introduce our new Version 3 MPLNET data. All sites in the network now feature eye-safe polarized backscatter MPL instruments, providing information on attenuated backscatter and particle shape. In addition to change with our signal data, we have an enhanced cloud product suite, a new PBL height product, and inclusion of the new AERONET lunar aerosol optical depth into MPLNET aerosol retrievals. A new quality flag process will be used to better describe all data products. Finally, a new data portal will provide near-real-time (NRT) access to all data products, including new quality assured NRT L1.5 products. Custom products developed for model specific applications will also be provided

Daytime Cirrus Cloud Top-of-Atmosphere Radiative Forcing Properties at a Midlatitude Site and their Global Consequence

One year of continuous ground-based lidar observations (2012) is analyzed for single-layer cirrus clouds at the NASA Micro Pulse Lidar Network site at the Goddard Space Flight Center to investigate top-of-the-atmosphere (TOA) annual net daytime radiative forcing properties. A slight positive net daytime forcing is estimated (i.e., warming): 0.070.67 W m(exp -2) in sample-relative terms, which reduces to 0.030.27 W m(exp -2) in absolute terms after normalizing to unity based on a 40% midlatitude occurrence frequency rate estimated from satellite data. Results are based on bookend solutions for lidar extinction-to-backscatter (20 and 30 sr) and corresponding retrievals of the 532-nm cloud extinction coefficient. Uncertainties due to cloud under sampling, attenuation effects, sample selection, and lidar multiple scattering are described. A net daytime cooling effect is found from the very thinnest clouds (cloud optical depth of less than or equal to 0.01), which is attributed to relatively high solar zenith angles. A relationship involving positive negative daytime cloud forcing is demonstrated as a function of solar zenith angle and cloud-top temperature. These properties, combined with the influence of varying surface albedos, are used to conceptualize how daytime cloud forcing likely varies with latitude and season, with cirrus clouds exerting less positive forcing and potentially net TOA cooling approaching the summer poles (not ice and snow covered) versus greater warming at the equator. The existence of such a gradient would lead cirrus to induce varying daytime TOA forcing annually and seasonally, making it a far greater challenge than presently believed to constrain the daytime and diurnal cirrus contributions to global radiation budgets

Overview of MPLNET Version 3 Cloud Detection

The National Aeronautics and Space Administration Micro Pulse Lidar Network, version 3, cloud detection algorithm is described and differences relative to the previous version are highlighted. Clouds are identified from normalized level 1 signal profiles using two complementary methods. The first method considers vertical signal derivatives for detecting low-level clouds. The second method, which detects high-level clouds like cirrus, is based on signal uncertainties necessitated by the relatively low signal-to-noise ratio exhibited in the upper troposphere by eye-safe network instruments, especially during daytime. Furthermore, a multitemporal averaging scheme is used to improve cloud detection under conditions of a weak signal-to-noise ratio. Diurnal and seasonal cycles of cloud occurrence frequency based on one year of measurements at the Goddard Space Flight Center (Greenbelt, Maryland) site are compared for the new and previous versions. The largest differences, and perceived improvement, in detection occurs for high clouds (above 5 km, above MSL), which increase in occurrence by over 5%. There is also an increase in the detection of multilayered cloud profiles from 9% to 19%. Macrophysical properties and estimates of cloud optical depth are presented for a transparent cirrus dataset. However, the limit to which the cirrus cloud optical depth could be reliably estimated occurs between 0.5 and 0.8. A comparison using collocated CALIPSO measurements at the Goddard Space Flight Center and Singapore Micro Pulse Lidar Network (MPLNET) sites indicates improvements in cloud occurrence frequencies and layer heights

Minimal impact electro-injection of cells undergoing dynamic shape change reveals calpain activation

AbstractThe ability of neutrophils to rapidly change shape underlies their physiological functions of phagocytosis and spreading. A major problem in establishing the mechanism is that conventional microinjection of substances and indicators interferes with this dynamic cell behaviour. Here we show that electroinjection, a “no-touch” point-and-shoot means of introducing material into the cell, is sufficiently gentle to allow neutrophils to be injected whilst undergoing chemokinesis and spreading without disturbing cell shape change behaviour. Using this approach, a fluorogenic calpain-1 selective peptide substrate was introduced into the cytosol of individual neutrophils undergoing shape changes. These data showed that (i) physiologically elevated cytosolic Ca2+ concentrations were sufficient to trigger calpain-1 activation, blockade of Ca2+ influx preventing calpain activation and (ii) calpain-1 activity was elevated in spreading neutrophil. These findings provide the first direct demonstration of a physiological role for Ca2+ elevation in calpain-1 activation and rapid cell spreading. Electroinjection of cells undergoing dynamic shape changes thus opens new avenues of investigation for defining the molecular mechanism underlying dynamic cell shape changes