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We show that SQUIRLS transcends previous state-of-the-art accuracy in classifying splice variants as assessed by rank analysis in simulated exomes, and is significantly faster than competing methods. SQUIRLS provides tabular output files for incorporation into diagnostic pipelines for exome and genome analysis, as well as visualizations that contextualize predicted effects of variants on splicing to make it easier to interpret splice variants in diagnostic settings.

To investigate the relationship between retinal fluid and vision in ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD).

Clinical cohort study using post hoc analysis of clinical trial data.

Setting HARBOR (NCT00891735) phase III, randomized, controlled trial.

917 patients aged ≥50 years with subfoveal nAMD associated with subretinal (SRF) and/or intraretinal fluid (IRF) at baseline, screening, or week 1.

Intravitreal ranibizumab 0.5 or 2.0 mg (all treatment arms pooled).

Mean best-corrected visual acuity (BCVA) and BCVA change from baseline at months (M)12/24 evaluated by presence/absence of SRF and/or IRF.

Baseline BCVA was higher with residual versus resolved SRF at M12 (mean [95% confidence interval (CI)], 58.8 letters [57.2 to 60.4] vs 53.5 [52.4 to 54.5]) and M24 (59.3 letters [57.8 to 60.8] vs 53.5 [52.5 to 54.5]). Mean BCVA change (adjusted for baseline) to M12 was greater with residual versus resolved SRF (mean difference [95% CI], +2.4 letters [+0.1 to +4.7]), but lower with residual versus resolved IRF (-3.5 letters [-5.8 to -1.2]). Eyes with residual SRF (no IRF) exhibited the largest mean BCVA gains (M12, +14.1 letters; M24, +13.2), followed by resolved SRF/IRF (M12, +10.6 letters; M24, +10.0), residual SRF/IRF (M12, +7.2 letters; M24, +8.5), and residual IRF only (M12, +5.5 letters; M24, +3.6).

Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual versus resolved SRF, and worse with residual versus resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management.

Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual versus resolved SRF, and worse with residual versus resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management.

To compare visual outcome and recurrence rates of eyes with non-infectious inflammatory CNV treated with or without anti-VEGF injections and immunosuppression.

Retrospective, non-randomized clinical study METHODS Participants Patients with CNV secondary to non-infectious inflammatory causes who attended uveitis clinics at Moorfields Eye Hospital between January 2000 and April 2016. Data was gathered from the clinical notes of all subjects examined in clinic.

change in best corrected visual acuity (BCVA), mean time to CNV recurrence, moderate vision loss (MVL; ≤ 20/50), severe vision loss (SVL; ≤20/200).

A total of 166 patients (204 eyes) with non-infectious inflammatory CNV were included in this study with a median follow-up of 6.9 years (IQR 2.9-11.7; 1652 eye-years). The mean BCVA at the time of CNV diagnosis was 0.38±0.05 logMAR (Snellen equivalent 20/47) in the eyes which received the first-line anti-VEGF treatment and 0.44±0.03 logMAR (Snellen equivalent 20/55) in the eyes on other treatment modd inflammatory CNV were at risk of vision loss. Those receiving early anti-VEGF injections achieved a better visual outcome and had a reduced risk of CNV recurrence. Oral corticosteroids also had an effect reducing the risk of recurrence in eyes previously treated.

To evaluate the presence of angle dysgenesis on ASOCT (ADoA) as a predictive factor in determining outcomes of selective laser trabeculoplasty (SLT).

A prospective clinical cohort study.

Patients with Juvenile onset open-angle glaucoma (JOAG) without angle dysgenesis on gonioscopy (ADoG).

JOAG patients with uncontrolled IOP, who were to undergo SLT, were evaluated for the presence or absence of ADoA, which was defined as the absence of Schlemm's canal (SC) and/or presence of hyper-reflective membrane (HM) over TM as identified on ASOCT before the SLT procedure. Further, the number of ASOCT B-scans in which SC was identified as present, were then quantified. Success of SLT was defined as a reduction of IOP by 20% or more from pre-laser value at 6-months follow-up without any further IOP-lowering medication or surgery. Only one repeat SLT was admissible for defining SLT success over the 6-month period. A successful reduction in IOP at six-month follow-up was correlated with the extent of ADoA.

In comparison to pre-SLT IOP, 57.1% (20/35) eyes showed more than 20% reduction in IOP at six months with a mean reduction of 7.6±1.8mmHg (29.6%). When all three observers agreed, SC was identified in 80% (18/20) eyes with success vs 26.6% (4/15) eyes with failure (p < 0.001). All (5/5) eyes with presence of HM showed failure (p < 0.001). All eyes (19/19) in which SC was present in >50% ASOCT B-scans (>25/50 scans/eye) showed success (p < 0.001). On a bias reduced regression analysis, the identification of SC on any two consecutive scans increased the chances of success at 6months by 8.3 times, while the identification of SC in >50% of ASOCT scans was associated with a 21.4 times greater chance of success.

The presence of SC on ASOCT is a strong predictor for successful IOP reduction after SLT in JOAG eyes.

The presence of SC on ASOCT is a strong predictor for successful IOP reduction after SLT in JOAG eyes.An outbreak of severe acute respiratory syndrome coronavirus 2 caused by the Gamma variant of concern infected 24/44 (55%) employees of a gold mine in French Guiana (87% symptomatic, no severe forms). The attack rate was 60% (15/25) among fully vaccinated miners and 75% (3/4) among unvaccinated miners without a history of infection.

Hepatitis-B virus (HBV) infection is an important health problem worldwide. HBV vaccine application varies according to the birth weight and gestational week in the neonatal period. This study aimed to reconsider delaying the administration of the HBV vaccine because the birth weight of newborns was very low.

The newborns with very low birth weight in the study group were babies weighing less than 2000g in the postnatal first month and at the time of administering HBV vaccine. Babies born at term from mothers who did not receive an HBV vaccine, had negative hepatitis B surface antibody levels, and were given HBV vaccine at birth were included in the study as a control group. The antibody levels against HBV vaccine were compared between these two groups.

The retrospective study included 60 participants (32 men and 28 women) grouped as control first vaccine weight (first vaccine weight was >2000g, control group, n =30) and case vaccine weight (first vaccine weight was <2000g, case group, n =30). The mean birth weight was 2976±84.8g and 1054±44.5g in the control and case groups, respectively. The first vaccine weight was 2030-3780g and 960-1900g in the control and case groups, respectively. The mean antibody level was 297.8±76.3IU/mL and 309.7±56.3IU/mL in the <1500g and >1500g groups, respectively. No significant difference was found in hepatitis antibody levels between the groups.

Further studies in larger samples are needed to confirm the efficacy and efficiency of postponement of hepatitis B vaccination in babies with a birth weight of <2000g.

Further studies in larger samples are needed to confirm the efficacy and efficiency of postponement of hepatitis B vaccination in babies with a birth weight of less then 2000 g.The writing process is a complex task involving dexterous manipulation of the writing instrument by the hand digits and biomechanical ergonomic factors that contribute to handwriting efficiency and productivity. Phorbol 12-myristate 13-acetate concentration We describe a pilot study using an instrumented writing apparatus - a sensor (pen) and a digitized writing surface (tablet) - to measure the pen-grip kinetics (digit forces) and the pen pressure applied to the tablet during a writing task. Eight elementary school students with no handwriting difficulties copied a short story. The mean digit forces on the pen were compared with the mean pen pressure on the tablet at five interval points. Results revealed that the digit forces on the pen were significantly stronger than the pen pressure on the tablet. Results also showed significantly less digit-force variability throughout the writing task than the pen-pressure variability on the writing surface, which significantly lessened toward the end of the writing task. link2 Information on these properties can broaden understanding of the elements that influence nonproficient handwriting in children with dysgraphia. Results also indicate the possible efficacy of a therapeutic tool for handwriting assessment and intervention using objective measurements during writing, warranting future studies with children with and without dysgraphia.Since the initial observation of increased immunoglobulin concentrations in the cerebrospinal fluid of multiple sclerosis (MS) patients in the 1940s, B cells have been considered to participate in the pathology of MS through the production of autoantibodies reactive against central nervous system antigens. link3 However, it is now recognized that B cells contribute to MS relapses via antibody-independent activities, including the presentation of antigens to T cells and the release of pro-inflammatory cytokines. In addition, the recent identification of B cell-rich follicle-like structures in the meninges of progressive MS patients suggests that the pathogenic roles of B cells also exist at the progressive phase of this disease. Recently, large-scale clinical trials have demonstrated the efficacy of B-cell depletion therapy using anti-CD20 antibodies in relapsing as well as primary progressive MS. B-cell depletion therapy has become an essential treatment option for MS based on its unique benefit to risk balance in relapsing MS, and because it is the only drug that has been shown to be effective in primary progressive MS to date.

This multicenter, parallel randomized, open study examined the effect of using vouchers and session reminders as an added element to outpatient treatment for drug use disorders in youth. It was hypothesized that being randomly assigned to a contingency management condition would lead to a reduction of psychiatric symptoms, and that this reduction would be mediated through abstinence and treatment completion.

A total of 460 participants aged 15 to 25 years from nine outpatient sites were randomized to one of four treatment conditions (standard treatment alone [STD], i.e., 12 sessions using motivational interviewing and cognitive behavioral therapy, STD plus vouchers for attendance [VOU], STD plus text reminders [REM], or STD plus vouchers and text reminders [REM + VOU]). Participants' symptoms of psychological distress were assessed using the YouthMap 12 instrument at intake, and at 3, 6, and 9 months post-treatment initiation. Interviewers were blinded to interventions.

114 participants were randomized to STD, 112 to REM, 113 to VOU, and 121 to VOU + REM.

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