Burning plasma achieved in inertial fusion.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Energy Principles of Scientific Breakeven in an Inertial Fusion Experiment.

Fusion "scientific breakeven" (i.e., unity target gain G_{target}, total fusion energy out > laser energy input) has been achieved for the first time (here, G_{target}∼1.5). This Letter reports on the physics principles of the design changes that led to the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce target gain greater than unity and exceeded the previously obtained conditions needed for ignition by the Lawson criterion. Key elements of the success came from reducing "coast time" (the time duration between the end of the laser pulse and implosion peak compression) and maximizing the internal energy delivered to the "hot spot" (the yield producing part of the fusion fuel). The link between coast time and maximally efficient conversion of kinetic energy into internal energy is explained. The energetics consequences of asymmetry and hydrodynamic-induced mixing were part of high-yield big radius implosion design experimental and design strategy. Herein, it is shown how asymmetry and mixing consolidate into one key relationship. It is shown that mixing distills into a kinetic energy cost similar to the impact of implosion asymmetry, shifting the threshold for ignition to higher implosion kinetic energy-a factor not normally included in most statements of the generalized Lawson criterion, but the key needed modifications clearly emerge.

Unravelling the impact of heat stress on daughter pregnancy rate in Mehsana buffalo through innovative breeding interventions.

Heat stress profoundly affects the reproductive success of buffaloes, which are vital for the dairy industry due to their unique anatomical and physiological characteristics, necessitating careful evaluation under such conditions. Hence, this guided our search for quantifying heat stress' impact on Mehsana buffaloes using the best THI model and evaluating sires' performance. Fertility records (days open converted to daughter pregnancy rate) were collected in the span of over 24 years, w.e.f. 1989 to 2012. Finally, 3070 records of first lactation cows, daughters of 117 sires from DURDA, Gujarat, India, were used in the analysis. Meteorological data were retrieved from IMD, Pune, to understand the relationship between daughter pregnancy rate (DPR) and heat stress indicators. Several heat stress models were compared based on R2, adjusted R2, AIC, and BIC values, and the impact of heat stress was quantified. The year was classified into different heat stress zones, viz., Non heat stress zone (NHSZ), Heat stress zone (HSZ), and critical heat stress zone (CHSZ), drawing from the findings of DPR and THI. The THI 4th model based on dry and wet bulb temperature was identified as the best-fit model, and DPR significantly changed (P < 0.01) by 1.14% per unit change in THI value based on the month of calving. The average EBVs of the sires for DPR were found to be 20.78% (NHSZ), 38.09% (HSZ), and 39.08% (CHSZ) using BLUP-SM and 20.78% (NHSZ), 37.30% (HSZ), and 38.87% (HSZ) using BLUP-AM. Subsequently, the optimum sire for each of the zones was prioritized. It is noteworthy that bulls that performed better in NHSZ did not perform as well in HSZ and CHSZ, and vice versa. This supports the possibility of evaluating bulls independently in each heat stress zone.

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model.

OBJECTIVES: A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model. METHODS: A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome. RESULTS: Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies. CONCLUSIONS: Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Multinational comparison study of aircraft pilot healthcare avoidance behaviour.

BACKGROUND: US and Canadian pilots are required to meet medical standards to secure their active flying status, but a subgroup exhibit healthcare avoidance behaviour due to fear of loss of that status. This phenomenon has the potential to impact pilot health, aeromedical screening and aviation safety. No international comparison study of pilot healthcare avoidance currently exists between US and Canadian pilots. AIMS: To compare the rate and subtypes of healthcare avoidance behaviour secondary to fear for loss of flying status between US and Canadian pilots. METHODS: A comparison analysis of data collected during two independent, non-probabilistic, cross-sectional internet surveys including any individual certified to perform flying duties in the USA (US survey) or Canada (Canadian survey). RESULTS: There were 4320 US pilots and 1415 Canadian pilots who completed informed consent and 3765 US pilots and 1405 Canadian pilots were included in the results. There were 56% of US pilots who reported a history of healthcare avoidance behaviour compared to 55% of Canadian pilots (P = 0.578). A multivariable logistic regression that included age, pilot type and gender showed that US pilots were slightly more likely than Canadian pilots to report this behaviour (odds ratio 1.22, 95% confidence interval 1.06-1.4). CONCLUSIONS: Healthcare avoidance behaviour due to fear of loss of flying status has a relatively high prevalence in both US and Canadian pilot populations.

Multiparameter flood hazard, socioeconomic vulnerability and flood risk assessment for densely populated coastal city.

In the current study, flood risk assessment of densely populated coastal urban Surat City, on the bank of the lower Tapi River in India, was conducted by combining the hydrodynamic model-based flood hazard and often neglected socioeconomic vulnerability. A two-dimensional (2D) hydrodynamic (HD) model was developed using physically surveyed topographic data and the existing land use land cover (LULC) of the study area (5248 km2). The satisfactory performance of the developed model was ascertained by comparing the observed and simulated water levels/depths across the river and floodplain. The 2D HD model outputs with geographic information system (GIS) applications were further used to develop probabilistic multiparameter flood hazard maps for coastal urban city. During a 100-year return period flood (Peak discharge = 34,459 m3/s), 86.5% of Surat City and its outskirt area was submerged, with 37% under the high hazard category. The north and west zones are the worst affected areas in Surat City. The socioeconomic sensitivity and adaptive capacity indicators were selected at the city's lowest administrative (ward) level. The socioeconomic vulnerability was evaluated by employing the robust data envelopment analysis (DEA) technique. Fifty-five of 89 wards in Surat City, covering 60% of the area under the jurisdiction of the Municipal Corporation, are highly vulnerable. Finally, the flood risk assessment of the city was conducted using a bivariate technique describing the distinctive contribution of flood hazard and socioeconomic vulnerability to risk. The wards adjoining the river and creek are at high flood risk, with an equal contribution of hazard and vulnerability. The ward-level hazard, vulnerability, and risk assessment of the city will help local and disaster management authorities to priorities high risk areas while planning flood management and mitigation strategies.

Spatiotemporal variability of extreme temperature indices and their implications over the heterogeneous river basin, India.

The current study on spatiotemporal variability of temperature presents a holistic approach for quantifying the joint space-time variability of extreme temperature indices over the physio-climatically heterogeneous Tapi River basin (TRB) using two unsupervised machine learning algorithms, i.e., principal component analysis (PCA) and cluster analysis. The long-term variability in extreme temperature indices, recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI), was evaluated for 1951-2016. The magnitude and statistical significance of the temporal trend in extreme temperature indices were estimated using non-parametric Sen's slope estimator and modified Mann Kendall (MMK) tests, respectively. The multivariate assessment of temporal trends using PCA resulted in four principal components (PCs) encapsulating more than 90% variability. The cluster analysis of corresponding PCs resulted in two spatial clusters exhibiting homogeneous spatiotemporal variability. Cluster 1 is characterized by significantly increasing hottest, very hot, and extremely hot days with rising average maximum temperature and intraday temperature variability. On the other hand, cluster 2 showed significantly rising coldest nights, mean minimum, mean temperature, and Tx37 with significantly decreasing intraday and interannual temperature variability, very cold, and extremely cold nights with reducing cold spell durations. The summertime heat stress computation revealed that the Purna sub-catchment of the Tapi basin is more vulnerable to various health issues and decreased work performance (> 10%) for more than 45 days per year. The current study dealing with the associated effects of rising temperature variability on crop yield, human health, and work performance would help policymakers formulate better planning and management strategies to safeguard society and the environment.

Metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

OBJECTIVES: The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer. MATERIAL AND METHODS: Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35mg) in 1mL olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4mg/kg and 2mg/kg), Met (200mg/kg) alone and in combination with Dox (4mg/kg). Met pre-treated DMBA control groups received Dox 4mg/kg and 2mg/kg. RESULTS: Met pre-treated groups treated with Dox exhibited a decrease in tumor incidence, tumor volume and increased survival rate than the DMBA group. Organ-to-body weight ratios and histopathology of heart, liver and lungs of Met pre-treated groups treated with Dox showed lesser toxicity than Dox treated DMBA control groups. There was a noteworthy decrease in malondialdehyde levels and a substantial increase in the levels of reduced glutathione together with a significant decrease in the levels of inflammatory markers like IL-6, IL-1ß and NF-κB in Met pre-treated groups treated with Dox. Histopathology of breast tumors revealed better control of tumors in Met pre-treated groups treated with Dox than DMBA control group. Immunohistochemistry and real-time PCR data revealed a significant reduction in Ki67 expression in Met pre-treated groups treated with Dox as compared to the DMBA control group. CONCLUSION: The present study suggests that metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

Simultaneous determination of emtricitabine, tenofovir alafenamide fumarate and dolutegravir sodium by validated stability-indicating RP-HPLC-DAD method.

OBJECTIVE: The purpose of this research was to develop and validate a stability-indicating RP-HPLC technique for simultaneous quantification of Emtricitabine (EMT), Tenofovir Alafenamide Fumarate (TEN), and Dolutegravir Sodium (DOL) in bulk and in their combined formulation. MATERIAL AND METHODS: The developed approach was done on Exterra C18 column (150×4.6mm, 5µm) and Methanol and Buffer (comprising 0.1 (v/v) of Triethylamine and o-phosphoric acid in water, pH 2.6) as mobile phase in the proportion of 75:25 (v/v), eluted at 1mL/min. The analytes were quantified using DAD detector at 265nm. RESULTS: The approach was validated in accordance with the ICH guidelines. Linearity, precision, accuracy, specificity, Limit of Detection (LOD), Limit of Quantitation (LOQ), and robustness were used to validate the proposed method. Linear response was found in the range of 500-1500µg/mL for EMT, 62.5-187.5µg/mL for TEN and 125-375µg/mL for DOL. The LOD values of EMT, TEN and DOL were found 91.78µg/mL, 10.47µg/mL and 19.28µg/mL correspondingly. The LOQ values of EMT, TEN and DOL were found and 278.11µg/mL, 31.74µg/mL and 58.42µg/mL correspondingly. The assay outcomes for all drugs were observed between 99.11-100.84%. To access the method's stability indicating capabilities, the drugs were exposed to various environmental (acid, alkaline, neutral, oxidative, photolytic and thermal) conditions. CONCLUSION: The established approach was considered to be accurate, linear, precise, specific, robust and it can be utilized to analyse the drugs mentioned in its tablet.

UNDERSTANDING THE VITAL DETERMINANTS SHAPING LEARNERS' PHYSICAL ACTIVITYAND PSYCHOEMOTIONAL WELLBEING IN THE COVID-19 PERIOD.

The Corona Virus (COV-19) epidemic significantly affected the educational environment, requiring a quick transition to distance and blended learning methods. This extraordinary disruption had an incredible impact on pupil's levels of physical activity (PA), psycho-emotional health (PEH) and engagement with academic material. The research aims to examine the vital determinants that influenced various areas of learners' lives during CoV-19. The purpose of this 600-person study was to collect data on the subjects' overall health and PA levels for the CoV-19 pandemic. The SPSS application was used to process the questionnaire's collected data. The information given reveals the respondents' degree of PA throughout the quarantine. According to the breakdown, 15% indicated low levels of PA, 39% reported medium levels and 46% reported high levels. The data show that, despite the respondents' different levels of PA, little PA predominated for most of them. The limitations of distance learning throughout quarantine and the prevalent recommendation of leaving residence for necessary reasons were blamed for this tendency. There were fewer prospects for higher-intensity PA due to these circumstances.

Measurement of Dark Ice-Ablator Mix in Inertial Confinement Fusion.

We present measurements of ice-ablator mix at stagnation of inertially confined, cryogenically layered capsule implosions. An ice layer thickness scan with layers significantly thinner than used in ignition experiments enables us to investigate mix near the inner ablator interface. Our experiments reveal for the first time that the majority of atomically mixed ablator material is "dark" mix. It is seeded by the ice-ablator interface instability and located in the relatively cooler, denser region of the fuel assembly surrounding the fusion hot spot. The amount of dark mix is an important quantity as it is thought to affect both fusion fuel compression and burn propagation when it turns into hot mix as the burn wave propagates through the initially colder fuel region surrounding an igniting hot spot. We demonstrate a significant reduction in ice-ablator mix in the hot-spot boundary region when we increase the initial ice layer thickness.

Hexagonal Prisms Form in Water-Ice Clouds on Mars, Producing Halo Displays Seen by Perseverance Rover.

Observations by several cameras on the Perseverance rover showed a 22° scattering halo around the Sun over several hours during northern midsummer (solar longitude 142°). Such a halo has not previously been seen beyond Earth. The halo occurred during the aphelion cloud belt season and the cloudiest time yet observed from the Perseverance site. The halo required crystalline water-ice cloud particles in the form of hexagonal columns large enough for refraction to be significant, at least 11 µm in diameter and length. From a possible 40-50 km altitude, and over the 3.3 hr duration of the halo, particles could have fallen 3-12 km, causing downward transport of water and dust. Halo-forming clouds are likely rare due to the high supersaturation of water that is required but may be more common in northern subtropical regions during northern midsummer.

The role of thalidomide in dermatology.

Thalidomide is a medication that has been in existence for over half a century, and has proven to be useful and effective in severe dermatological conditions. For dermatologists, the ability of thalidomide to reduce the levels of the cytokine tumour necrosis factor-α, along with its immunomodulatory and anti-angiogenic properties, is of great significance, with the added advantage of being an oral medication. Its use is of course strictly monitored, owing to its potential adverse effects (AEs), particularly teratogenicity, with precautions taken to ensure its safe and correct use by both prescriber and patient. In this review, we look at the background and mechanism of action of thalidomide, provide an overview of conditions it can be used for with case examples, explain the potential AEs and monitoring requirements, and discuss future developments.

Patient outcomes following transfer between intensive care units during the COVID-19 pandemic.

Transferring critically ill patients between intensive care units (ICU) is often required in the UK, particularly during the COVID-19 pandemic. However, there is a paucity of data examining clinical outcomes following transfer of patients with COVID-19 and whether this strategy affects their acute physiology or outcome. We investigated all transfers of critically ill patients with COVID-19 between three different hospital ICUs, between March 2020 and March 2021. We focused on inter-hospital ICU transfers (those patients transferred between ICUs from different hospitals) and compared this cohort with intra-hospital ICU transfers (patients moved between different ICUs within the same hospital). A total of 507 transfers were assessed, of which 137 met the inclusion criteria. Forty-five patients underwent inter-hospital transfers compared with 92 intra-hospital transfers. There was no significant change in median compliance 6 h pre-transfer, immediately post-transfer and 24 h post-transfer in patients who underwent either intra-hospital or inter-hospital transfers. For inter-hospital transfers, there was an initial drop in median PaO2 /FI O2 ratio: from median (IQR [range]) 25.1 (17.8-33.7 [12.1-78.0]) kPa 6 h pre-transfer to 19.5 (14.6-28.9 [9.8-52.0]) kPa immediately post-transfer (p < 0.05). However, this had resolved at 24 h post-transfer: 25.4 (16.2-32.9 [9.4-51.9]) kPa. For intra-hospital transfers, there was no significant change in PaO2 /FI O2 ratio. We also found no meaningful difference in pH; PaCO2 ;, base excess; bicarbonate; or norepinephrine requirements. Our data demonstrate that patients with COVID-19 undergoing mechanical ventilation of the lungs may have short-term physiological deterioration when transferred between nearby hospitals but this resolves within 24 h. This finding is relevant to the UK critical care strategy in the face of unprecedented demand during the COVID-19 pandemic.

Screening of osmotic stress-tolerant bacteria for plant growth promotion in wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought conditions.

Drought stress adversely affects plant growth and productivity. Therefore, the application of plant growth-promoting bacteria is a viable option for combating drought resistance in crops. In this study, 144 bacteria were isolated from the Kutch desert soil in Gujarat. Based on osmotic stress tolerance and PGP properties, two strains, Bacillus tequilensis (KS5B) and Pseudomonas stutzeri (KS5C) were tested for their effect on wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought stress conditions. Inoculation with osmotic stress-tolerant bacteria showed 15·15-29·27% enhancement in root length of wheat and 15·27-32·59% in brinjal plants. Similarly, the enhancement of shoot length ranged from 14·72 to 37·70% for wheat and 59·39-95·94% for brinjal plants. Furthermore, the inoculated plants showed significant improvement in chlorophyll content and antioxidant properties such as proline, peroxidase and polyphenol oxidase activity compared to the control. Therefore, the bacterial strains identified in this study can be used to mitigate drought stress and enhance plant biomass.