Fluxes over Varanasi during intensive observation period of MONTBLEX-90

ABSTRACT. MONTBLEX-90 data for an Intensive Observational Period (IOP) was extracted to investigate the thunderstorm and its impacts on surface layer at Varanasi on 27 July 1990. Sensible heat flux has been computed by profile, aerodynamic and eddy correlation methods. In addition to that. momentum and moisture fluxes have been computed for comparative diagnosis of situations before, at the time and after thunderstorm, Monin-Obukhov similarity theory has been used for quantification of the fluxes. Findings indicate that surface is more buoyant at the time of thunderstorm. Under this influence, maxima of moisture and momentum fluxes occur at the tin1e of thunderstorm. However, heat flux was found to be maximum before the thunderstorm, The results provide an understanding of surface layer turbulent transfer during stable and unstable conditions.

Does Confinement Affect Treatment Dropout Rates in Patients With Gambling Disorder? A Nine-Month Observational Study

Background and Aims: COVID-19 pandemic and confinement have represented a challenge for patients with gambling disorder (GD). Regarding treatment outcome, dropout may have been influenced by these adverse circumstances. The aims of this study were: (a) to analyze treatment dropout rates in patients with GD throughout two periods: during and after the lockdown and (b) to assess clinical features that could represent vulnerability factors for treatment dropout.Methods: The sample consisted of n=86 adults, mostly men (n=79, 91.9%) and with a mean age of 45years old (SD=16.85). Patients were diagnosed with GD according to DSM-5 criteria and were undergoing therapy at a Behavioral Addiction Unit when confinement started. Clinical data were collected through a semi-structured interview and protocolized psychometric assessment. A brief telephone survey related to COVID-19 concerns was also administered at the beginning of the lockdown. Dropout data were evaluated at two moments throughout a nine-month observational period (T1: during the lockdown, and T2: after the lockdown).Results: The risk of dropout during the complete observational period was R=32/86=0.372 (37.2%), the Incidence Density Rate (IDR) ratio T2/T1 being equal to 0.052/0.033=1.60 (p=0.252). Shorter treatment duration (p=0.007), lower anxiety (p=0.025), depressive symptoms (p=0.045) and lower use of adaptive coping strategies (p=0.046) characterized patients who abandoned treatment during the lockdown. Briefer duration of treatment (p=0.001) and higher employment concerns (p=0.044) were highlighted in the individuals who dropped out after the lockdown. Treatment duration was a predictor of dropout in both periods (p=0.005 and p<0.001, respectively).Conclusion: The present results suggest an impact of the COVID-19 pandemic on treatment dropout among patients with GD during and after the lockdown, being treatment duration a predictor of dropout. Assessing vulnerability features in GD may help clinicians identify high-risk individuals and enhance prevention and treatment approaches in future similar situations.

Understanding of an Iceberg Breaking Off Event Based on Ice-Front Motion Analysis of Amery Ice Shelf, Antarctica

On 26 September 2019, a massive iceberg broke off the west side of the Amery Ice Shelf (AIS) in East Antarctica. Since 1973, the AIS calving front has steadily advanced at a rate of 1.0 km yr−1. However, the advancement rate of the central portion of the AIS increased dramatically during 2012–2015, which indicates a velocity increase prior to the calving event. Eight calving front locations from 1973 to 2018 were mapped to investigate the advancement rate of AIS over the entire observational period. Additionally, the propagation of rift A was observed unstable from 2012 to 2015. The westward propagation rate of rift A1 increased to 3.7 km yr−1 from 2015 to 2017, which was considerably faster than the other rifts near the AIS calving front. The increased advancement rate and the increasing propagation magnitude of at least one active rift appear to be precursors of this large calving event.

Reactogenicity of COVID-19 vaccine in hemodialysis patients: a single-center retrospective study

Introduction Some hemodialysis patients are reluctant to COVID-19 for the development of adverse events (AEs). The aim of this study was to verify the safety of mRNA-1273 vaccine in hemodialysis patients. Methods We conducted a retrospective analysis of in-center hemodialysis patients who underwent mRNA-1273 vaccine from March 1st to April 30th, 2021. All AEs occurring after the first and the second doses were collected and classified as local or systemic. Results Overall, 126 patients on chronic maintenance dialysis were vaccinated with two doses of mRNA-1273 vaccine. Mean age was 68 (IQR, 54,7-76) years and 53.6% of patients were aged ≥ 65 years. During the observational period of 68 (IQR, 66-70) days, AEs occurred in 57.9% and 61.9% of patients after the first dose and second dose, respectively. The most common AEs were: injection-site pain (61.9%), erythema (4.8%), itching (4.8%), swelling (16.7%), axillary swelling/tenderness (2.4%), fever (17.5%) headache (7.9%), fatigue (23.8%), myalgia (17.5%), arthralgia (12.7%), dyspnoea (2.4%); nausea/ vomiting (7.1%), diarrhoea (5.6%), shivers (4%) and vertigo (1.6%). The rates of local AEs were similar after the first and second doses (P=0.8), whereas systemic AEs occurred more frequently after the second dose (P=0.001). Fever (P=0.03), fatigue (P=0.02) and nausea/vomiting (P=0.03) were significantly more frequent after the second dose of vaccine. There were no age-related differences in the rate of AEs. Overall, vaccine-related AEs in hemodialysis patients seem lower than in the general population. Conclusion RNA-1273 vaccine is associated with the development of transient AEs after the first (57.9%) and second dose (61.9%) in patients on chronic maintenance dialysis. Systemic AEs were more common after the second dose. Overall, all AEs lasted for a few days, without any apparent sequelae.

Daratumumab As a Treatment for Adult Immune Thrombocytopenia: A Phase II Study with Safety Run-in (the DART Study)

Background: Immune thrombocytopenia (ITP) is characterized by antibody-mediated platelet destruction and impaired platelet production. Residual long-lived autoreactive plasma cells may be a source of treatment resistance in autoimmune cytopenias. Antiplatelet-specific plasma cells have been detected in the spleen of the rituximab refractory ITP patients. These cells can also migrate and reside in bone marrow as long-lived plasma cells. Daratumumab, an anti-CD38 antibody, targets plasma cells and is approved for the treatment of multiple myeloma. Daratumumab has been successfully used to treat refractory autoimmune cytopenias in children and a few cases of post-transplant autoimmune cytopenias and refractory SLE in adults. We hypothesized that long-lived autoreactive plasma cells may be the source of treatment failure in some ITP patients. Based on that, we initiated a multicenter, open-label, dose-escalating phase II study with a safety run-in to evaluate the safety and efficacy of daratumumab in patients with ITP (NCT04703621). The first 3 patients were included in the safety run-in during Jan - May 2021. Study design and methods: Main inclusion criteria include age ≥18, primary ITP with a platelet count of ≤30X109/L, failure of corticosteroid therapy, and at least one second-line therapy including rituximab and/or TPO-RA. Main exclusion criteria include active bleeding, secondary ITP, concomitant autoimmune hemolytic anemia. Twenty-one patients will be included in the study. The safety run-in phase includes 3 patients who receive 4 weekly subcutaneous daratumumab injections followed by a 4-week observational period. Enrollment of the next patient in this phase occurs after the previous patient has completed treatment and an observational period. In cohort 1, 9 patients will receive 8 weekly injections. If the response rate is <100% and no severe adverse events appear, the subsequent 9 patients will receive 8 weekly daratumumab injections followed by 2 injections administered every other week. Standard premedication before all daratumumab injections consists of antihistamine, corticosteroid (methylprednisolone 100 mg or equivalent before the 1 st daratumumab injection and 60 mg or equivalent before subsequent injections), and paracetamol. Rescue ITP medications are allowed during the first 8 weeks of the study. Steroid or TPO-RA (eltrombopag or romiplostim) dosing must remain stable during the 2 weeks preceding the inclusion. Dose escalation is not allowed during the study. The primary endpoint is a platelet count >50x10 9/L in 2 measurements 12 weeks after treatment initiation for cohort 1, and 16 weeks for cohort 2, without rescue therapy after week 8. Safety will be assessed by the incidence and severity of adverse events. Secondary endpoints will include the number of weeks with platelet count >50x10 9/L between the end of treatment and end of study without rescue therapy or dose increments of corticosteroids. Time to treatment failure (TTF) is defined as time to first platelet count <30x10 9/L or administration of any platelet elevating therapy after achieving response. Exploratory endpoints include: role of anti-GPIIb/IIIa and Ib antibodies; serial characterization of various subsets of immunocompetent cells in the bone marrow and blood; measurement of HRQoL and fatigue Statistics: The primary outcome (treatment response) will be reported separately for each cohort and the entire study population, expressed by absolute numbers and rates with the corresponding 95% confidence interval. Daratumumab treatment will be considered "successful" if we observe a response rate of 30% or higher. Current enrollment status: As of July 10, 2021, 2 sites are open. Two patients have completed the safety run-in; one is close. One/two responded to treatment at week 12. Platelet response in all 3 patients is shown in Figure 1. No serious or grade 3 adverse events were reported. Cohort 1 will start in August 2021. Figure 1 Figure 1. Disclosures Tsykunova: Ablynx: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sobi: Consultancy; Sanofi: Consultancy. Holme: bayer, Octapharma, Pfizer: Other: support to institution, Research Funding; Bayer, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda, Sobi: Consultancy, Honoraria. Tran: Astra Zeneca: Consultancy; Novartis, Janssen, Abbvie, Takeda, CSL Bering: Consultancy. Tvedt: Ablynx,Alexion, Novartis: Membership on an entity's Board of Directors or advisory committees. Michel: Amgen,Novartis,UCB,Argenx,Rigel: Honoraria. Frederiksen: Novartis: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Alexion: Research Funding; Gilead: Research Funding. Bussel: CSL: Other: DSMB; UCB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Principia/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; UptoDate: Honoraria; RallyBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova/Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Momenta/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kuter: Rubius: Current equity holder in publicly-traded company; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Up-to-Date: Patents & Royalties: Up-To-Date. Ghanima: Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Griffols, Sanofi: Honoraria; Bayer, BMS/Pfizer: Research Funding; Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Griffols, UCB, Argenx: Consultancy.

Superiority of mosapride citrate to picosulfate sodium as a laxative for withdrawal from regular enemas in children with severe functional constipation

Background: Severe functional constipation (FC) with low bowel movement frequency (BMF) of ?1 day/week and hard stools oftenrequires regularly repeated enemas or often leads to enema dependency (ED). Aim: The current study aimed to compare the efficacy of mosapride citrate (Mo) with the traditional stimulant laxative picosulfate sodium (Pi) for withdrawal from ED in children with severe FC. Results: Twenty-four treatment-naïve patients who met the Rome IV diagnostic criteria for FC seen at our center for 8 years from 2012 were enrolled. Glycerin enema was repeated until the BMF was ?3.5 days/week. Simultaneously, Mo at 0.3 mg/kg/day (n=11) or Pi at 0.25 mg/kg/day (n=13) was administered concomitantly with magnesium oxide or lactulose. The proportion of withdrawal from ED was significantly higher in the Mo group than Pi group during the 4 months observational period (90.9% vs. 46.2%, respectively; p=0.034) and shorter in time to withdraw from ED (0 vs. 3.5 months, respectively; p=0.015). Conclusion: Mo is more effective than Pi for withdrawal from ED in children with severe FC.

Alpha-synuclein alters the faecal viromes of rats in a gut-initiated model of Parkinson’s disease

Parkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study’s five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development.

Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study

Background Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. Methods PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). Results Overall, 190 patients with a median age of 61 years (range: 22.0–96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48–11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). Conclusions Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

Efficacy of Neuro-Psychomotor Approach in Children Affected by Autism Spectrum Disorders: A Multicenter Study in Italian Pediatric Population

Background: Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and reciprocal communication. ASD affects about 1% of the general population and is associated with substantial disability and economic loss. A variety of approaches to improve the core deficits and lives of people with ASD have been developed, including behavioral, developmental, educational, and medical interventions. The main objective of this study was to evaluate the efficacy of a neuro-psychomotor approach in children affected by ASD. Methods: The sample consisted of 84 children (66 males, mean age 56.9 ± 15.8 months) affected by ASD assessed between September 2020 to March 2021. The trained therapist was asked to complete the ASD behavior inventory (ASDBI) test at baseline (T0) (September 2020) and after six months (T1) (March 2021) to assess the child’s evolution over the observational period. The study was carried out in southern Italy (Campania Region). Results: ASD children showed a significant improvement for AUTISM composite after 6 months of neuro-psychomotor treatment (T1) compared to baseline (65.4 ± 12.2 vs. 75.8 ± 11.5, p < 0.0001). In particular, significant changes were observed for such domains as the problems of excitability (ECCIT), aggression (AGG), behaviors in social relations (RELSOC), expressive (all p < 0.001), sense/perceptual contact modes (SENS) (p = 0.0007), ritualisms/resistance to changes (RIT) (p = 0.0002), pragmatic/social problems (PPSOC) (p = 0.0009), specific fears (FEARS) (p = 0.01), and learning and memory (AMLR) (p = 0.0007). No differences for the domains Semantic/pragmatic problems (PPSEM) and language (LESP) were found. Conclusions: Our preliminary results suggest the usefulness of the neuro-psychomotor treatment in children with ASD. Although promising, these findings need to be tested further to better understand the long-term effects of this specific type of approach.

Partner loss and its effect on frailty trajectories: results from the 13-year follow-up Survey of Health, Ageing and Retirement in Europe (SHARE)

BackgroundFrailty is a geriatric syndrome closely linked to a variety of adverse health outcomes. Thus, it is important to identify factors associated with the development of frailty. It was the aim of this study to examine, if, and to what extent partner loss, a highly stressful life event, affects frailty trajectories of community dwelling adults aged 50 or older.MethodsUsing six waves of panel data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we investigated the effect of partner loss on frailty trajectories estimating growth curve models. Our sample included 183 502 observations of 83 494 community-dwelling individuals aged 50 or older from 21 European countries collected between 2004 and 2017. Frailty was measured using the validated sex-specific SHARE-Frailty-Instrument including muscular weakness, unintended weight loss, decrease in walking capacity, low physical activity and exhaustion.ResultsOur sample contained 79 874 participants who lived in a partnership during their entire observational period and 3620 participants who lost their partner during their observational period. Both men (β=0.184 (95% CI: −0.017 to 0.386), p=0.073) and women (β=0.237 (95% CI: 0.106 to 0.369), p<0.001) showed initial effects of partner loss on frailty, but while only women gradually recovered over time (β=−0.023 (95% CI: −0.039 to −0.008), p=0.002), among men, the effect of partner loss persisted (β<0.001 (95% CI: −0.029 to 0.029), p=0.998).ConclusionThis study revealed that partner loss is followed by elevated frailty. However, while women’s frailty tended to recover from partner loss over time, men’s frailty remained elevated. Notable individual differences in the response of frailty trajectories to partner loss suggest the existence of effect modifiers.