Highlights d The subdominant NVDP minor repeats of PfCSP are neutralizing epitopes d Potent mAbs with junctional and NANP cross-reactivity bind PfCSP in two steps d Cytotoxic PfCSP mAbs kill sporozoites in the liver d PfCSP mAbs prevent sporozoites from exiting liver sinusoids to infect hepatocytes

Novel approaches to care delivery that leverage clinical and community resources could improve body mass index (BMI) and family-centered outcomes.OBJECTIVE To examine the extent to which 2 clinical-community interventions improved child BMI z score and health-related quality of life, as well as parental resource empowerment in the Connect for Health Trial. DESIGN, SETTING, AND PARTICIPANTSThis 2-arm, blinded, randomized clinical trial was conducted from June 2014 through March 2016, with measures at baseline and 1 year after randomization. This intent-to-treat analysis included 721 children ages 2 to 12 years with BMI in the 85th or greater percentile from 6 primary care practices in Massachusetts.INTERVENTIONS Children were randomized to 1 of 2 arms: (1) enhanced primary care (eg, flagging of children with BMI Ն 85th percentile, clinical decision support tools for pediatric weight management, parent educational materials, a Neighborhood Resource Guide, and monthly text messages) or (2) enhanced primary care plus contextually tailored, individual health coaching (twice-weekly text messages and telephone or video contacts every other month) to support behavior change and linkage of families to neighborhood resources. MAIN OUTCOMES AND MEASURESOne-year changes in age-and sex-specific BMI z score, child health-related quality of life measured by the Pediatric Quality of Life 4.0, and parental resource empowerment. RESULTS At1year,weobtainedBMIzscoresfrom664children(92%)andfamily-centeredoutcomes from 657 parents (91%). The baseline mean (SD) age was 8.0 (3.0) years; 35% were white (n = 252), 33.3% were black (n = 240), 21.8% were Hispanic (n = 157), and 9.9% were of another race/ethnicity (n = 71). In the enhanced primary care group, adjusted mean (SD) BMI z score was 1.91 (0.56) at baselineand1.85(0.58)at1year,animprovementof−0.06BMIzscoreunits(95%CI,−0.10to−0.02) from baseline to 1 year. In the enhanced primary care plus coaching group, the adjusted mean (SD) BMI z score was 1.87 (0.56) at baseline and 1.79 (0.58) at 1 year, an improvement of −0.09 BMI z score units (95% CI, −0.13 to −0.05). However, there was no significant difference between the 2 intervention arms (difference, −0.02; 95% CI, −0.08 to 0.03; P = .39). Both intervention arms led to improved parental resource empowerment: 0.29 units (95% CI, 0.22 to 0.35) higher in the enhanced primary care group and 0.22 units (95% CI, 0.15 to 0.28) higher in the enhanced primary care plus coaching group. Parents in the enhanced primary care plus coaching group, but not in the enhanced care alone group, reported improvements in their child's health-related quality of life (1.53 units; 95% CI, 0.51 to 2.56). However, there were no significant differences between the intervention arms in either parental resource empowerment (0.07 units; 95% CI, −0.02 to 0.16) or child health-related quality of life (0.89 units; 95% CI, −0.56 to 2.33). CONCLUSIONS AND RELEVANCETwo interventions that included a package of high-quality clinical care for obesity and linkages to communit...

HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, randomized, double-blind, dose-escalation, placebo-controlled first-in-human trial of the HIV-1 V2-glycan-specific antibody PGDM1400 alone or in combination with the V3-glycan-specific antibody PGT121 in 24 adults without HIV in part 1, as well as a multi-center, open-label trial of the combination of PGDM1400, PGT121 and the CD4-binding-site antibody VRC07-523LS in five viremic adults living with HIV not on antiretroviral therapy (ART) in part 2 (NCT03205917). The primary endpoints were safety, tolerability and pharmacokinetics for both parts and antiviral activity among viremic adults living with HIV and not on ART for part 2 of the study. The secondary endpoints were changes in CD4+ T cell counts and development of HIV-1 sequence variations associated with PGDM1400, PGT121 and VRC07-523LS resistance in part 2. Intravenously administered PGDM1400 was safe and well-tolerated at doses up to 30 mg kg−1 and when given in combination with PGT121 and VRC07-523LS. A single intravenous infusion of 20 mg kg−1 of each of the three antibodies reduced plasma HIV RNA levels in viremic individuals by a maximum mean of 2.04 log10 copies per ml; however, viral rebound occurred in all participants within a median of 20 days after nadir. Rebound viruses demonstrated partial to complete resistance to PGDM1400 and PGT121 in vitro, whereas susceptibility to VRC07-523LS was preserved. Viral rebound occurred despite mean VRC07-523LS serum concentrations of 93 µg ml−1. The trial met the pre-specified endpoints. Our data suggest that future bNAb combinations likely need to achieve broad antiviral activity, while also maintaining high serum concentrations, to mediate viral control.

Family-centered childhood obesity interventions have been found to be effective. We describe the use of telehealth for tailored behavior change support in a family-centered randomized trial. Children of 2 to 12 years with body mass index ≥85th percentile were randomized to Enhanced Primary Care (EPC) or Enhanced Primary Care + Coaching (EPC + C). EPC + C received 6 health coach visits (in-person or by video or phone call) over 1 year. Telehealth modalities included interactive text messaging, video calls, and an online community resource map. There were 360 children randomized to the EPC + C arm; 87% of parents completed ≥1 health coaching contacts. Overall, 93% parents were sent text messages of which 99% responded at least once. About 72% parents were very satisfied with the message content and 97% were satisfied with information provided about community health resources. The high level of participant engagement and satisfaction suggests that telehealth is feasible and acceptable in family-centered childhood obesity programs.