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Abstract Context Postbariatric hypoglycemia (PBH), characterized by enteroinsular axis overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric surgery for which there is no approved therapy. Objective To evaluate efficacy and safety of avexitide [exendin (9-39)], a glucagon-like peptide-1 antagonist, for treatment of PBH. Methods A multicenter, Phase 2, randomized, placebo-controlled crossover study (PREVENT). Eighteen female patients with PBH were given placebo for 14 days followed by avexitide 30 mg twice daily and 60 mg once daily, each for 14 days in random order. The main outcome measures were glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and hypoglycemic events captured by self-monitoring of blood glucose (SMBG), electronic diary, and blinded continuous glucose monitoring (CGM). Results Compared with placebo, avexitide 30 mg twice daily and 60 mg once daily raised the glucose nadir by 21% (P = .001) and 26% (P = .0002) and lowered the insulin peak by 23% (P = .029) and 21% (P = .042), corresponding to 50% and 75% fewer participants requiring rescue during MMTT, respectively. Significant reductions in rates of Levels 1 to 3 hypoglycemia were observed, defined, respectively, as SMBG <70 mg/dL, SMBG <54 mg/dL, and a severe event characterized by altered mental and/or physical function requiring assistance. CGM demonstrated reductions in hypoglycemia without induction of clinically relevant hyperglycemia. Avexitide was well tolerated, with no increase in adverse events. Conclusion Avexitide administered for 28 days was well tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters, reinforcing the targeted therapeutic approach and demonstrating durability of effect. Avexitide may represent a first promising treatment for patients with severe PBH.

In this paper, we construct the inter-couplings and analyze the structural controllability of interdependent networks with known directed subnets. Firstly, we divide the interdependent network into a leader-system and a follower-system. The leader-system is proved to be certainly controllable, so we focus on constructing inter-couplings between two follower-subsystems and analyzing the structural controllability of the follower-system when the positions and the number of the leaders are fixed. Secondly, based on Kalman rank criterion, PBH rank criterion, as well as the graph maximum matching algorithm, combined with the controllable structure decomposition algorithm, several sufficient or necessary conditions for the structural controllability of the topological isomorphic follower-system are proposed to guarantee whether the follower-system and interdependent network are controllable or not. All the conditions provided in this paper also are suitable for the networks with undirected subnets. Finally, we take two examples to illustrate the feasibility and effectiveness of our theoretical conclusions.

In deep drawing process, excessive mass flow causes wrinkling and insufficient mass flow causes fracture. Blank holder has direct influence on mass flow into die cavity. In this study, the effect of pulsating blank holder by using a new mechanical system has been investigated for improving the formability of aluminum alloy. Also, this paper presents a systematic methodology for developing second-order statistical model to show the relationship between drawing depth and input variables (frequency of blank holder, amplitude of blank holder movement, and velocity of punch movement). The obtained model was used to analyze the effect of input parameters on performance of pulsating blank holder. The results show that the pulsating blank holder in comparison with static one can increase significantly the limiting drawing ratio of deep drawing process about 11.53%. The optimized drawing depth value is subsequently obtained from the mathematical model.

Though widely used, resting heart rate (RHR), as measured by a wearable device, has not been previously evaluated in a large cohort against a variety of important baseline characteristics. This study aimed to assess the validity of the RHR measured by a wearable device compared against the gold standard of ECG (electrocardiography), and assess the relationships between device-measured RHR and a broad range of clinical characteristics. The Project Baseline Health Study (PHBS) captured detailed demographic, occupational, social, lifestyle, and clinical data to generate a deeply phenotyped cohort. We selected an analysis cohort within it, which included participants who had RHR determined by both ECG and the Verily Study Watch (VSW). We examined the correlation between these simultaneous RHR measures and assessed the relationship between VSW RHR and a range of baseline characteristics, including demographic, clinical, laboratory, and functional assessments. From the overall PBHS cohort (N=2502), 875 (35%) participants entered the analysis cohort (mean age 50.9, SD 16.5 years; n=519, 59% female and n=356, 41% male). The mean and SD of VSW RHR was 66.6 (SD 11.2) beats per minute (bpm) for female participants and 64.4 (SD 12.3) bpm for male participants. There was excellent reliability between the two measures of RHR (ECG and VSW) with an intraclass correlation coefficient of 0.946. On univariate analyses, female and male participants had similar baseline characteristics that trended with higher VSW RHR: lack of health care insurance (both P<.05), higher BMI (both P<.001), higher C-reactive protein (both P<.001), presence of type 2 diabetes mellitus (both P<.001) and higher World Health Organization Disability Assessment Schedule (WHODAS) 2.0 score (both P<.001) were associated with higher RHR. On regression analyses, within each domain of baseline characteristics (demographics and socioeconomic status, medical conditions, vitals, physical function, laboratory assessments, and patient-reported outcomes), different characteristics were associated with VSW RHR in female and male participants. RHR determined by the VSW had an excellent correlation with that determined by ECG. Participants with higher VSW RHR had similar trends in socioeconomic status, medical conditions, vitals, laboratory assessments, physical function, and patient-reported outcomes irrespective of sex. However, within each domain of baseline characteristics, different characteristics were most associated with VSW RHR in female and male participants. ClinicalTrials.gov NCT03154346; https://clinicaltrials.gov/study/NCT03154346.

Presently, most of the common placement methods of actuators are based on the structural response and system energy to select the optimal locations. In these methods, the contribution of controllability and the energy of seismic excitations to each mode of the structure are not considered, and a large number of cases need to be calculated. To solve this problem, the Clough–Penzien spectral model is combined with the Luenberger observable normal form of the system to calculate the energy of each state. The modal disturbance degree, considering modal energy and controllability, is defined by using the controllability gramian matrix and PBH system controllability index, and the modes are divided into the main disturbance modes (MDMs) and the secondary disturbance modes (SDMs). A novel optimal placement method of actuators based on modal controllability degree is proposed, which uses MDMs as the main control modes. The optimal placement of actuators and the vibration control simulation of a 20-story building model are carried out. The results show that the vibration reduction effect of the proposed placement method is significantly better than that of the method of uniformly distributed actuators (Uniform method) and the classical placement method of actuators based on the system controllability gramian matrix (Classical method).

To evaluate remote participant engagement in a clinical study over time, based on data from the Project Baseline Health Study (PBHS), a hybrid in-person and virtual study. The PBHS enrolled 2,502 adult US residents from March 3, 2017 to April 26, 2019, with a ≤5-year follow-up. We summarized 4-year retention and rates of longitudinal patient-reported outcome survey completion. We investigated participant characteristics for their associations with quarterly remote survey completion using regression models. Of the total participants (  = 2,502), 94% remained enrolled after 4 years and 60% completed all annual visits; 2,490 participants stayed enrolled for at least one quarter. The median (IQR) number of remote electronic survey sets completed was 8 (3-12), of a possible 16. Age [odds ratio (OR), >70 vs. ≤30 years: 2.56; 95% CI: 2.24-2.94] and education (OR, advanced degree vs. ≤high school: 1.36; 95% CI: 1.22-1.52) were positively associated with remote survey completion. Participants with lower odds of completion were Black (OR vs. White: 0.73; 95% CI: 0.67-0.80), Hispanic (OR vs. non-Hispanic: 0.84; 95% CI: 0.77-0.93), or had at least mild symptoms of depression (OR vs. without: 0.90; 95% CI: 0.84-0.96) or anxiety (OR vs. without: 0.84; 95% CI: 0.78-0.90). Overall, 94% of PBHS participants remained enrolled after four years. Age, race, ethnicity, income, education, and symptomatic depression/anxiety were significantly associated with longitudinal remote questionnaire completion. These findings on engagement over time may inform future longitudinal study design. Clinicaltrials.gov, identifier (NCT03154346).

Two weaknesses of Ambridge, Pine, and Lieven’s (AP&L) argument against universal grammar are discussed in this commentary. First, their article treats the prosodic bootstrapping hypothesis (PBH) as a nativist theory, but PBH is entirely neutral with respect to the nativism-empiricism debate. Additional discussion of the plausibility of PBH is presented. Second, the rigor that AP&L direct toward nativist ideas must also be directed at empiricist claims. An understanding of how children acquire language will require nativist ideas, empiricist ideas, and ideas that are neutral on this dimension.*

Aggregates produced from finely ground waste glass [Growstones (GS); Earthstone Corp., Santa Fe, NM] have been proposed to adjust the physical properties of peat-based substrates. The GS had a total pore space (TPS) of 87.4% (by volume), which was higher than that of sphagnum peat and perlite but was similar to that of parboiled fresh rice hulls (PBH). The GS had an air-filled pore space (AFP) of 53.1%, which was higher than that of sphagnum peat and perlite but lower than that of PBH. At 34.3%, GS had a lower water-holding capacity (WHC) than sphagnum peat but a higher WHC than either perlite or PBH. The bulk density of GS was 0.19 g·cm–3 and was not different from that of the perlite but was higher than that of sphagnum peat and PBH. The addition of at least 15% GS to sphagnum peat increased the AFP of the resulting peat-based substrate. Substrates containing 25% or 30% GS had a higher AFP than substrates containing equivalent amounts of perlite but a lower AFP than substrates containing equivalent PBH. Substrates containing 20% or more GS had a higher WHC than equivalent perlite- or PBH-containing substrates. Growth of ‘Cooler Grape’ vinca (Catharanthus roseus), ‘Dazzler Lilac Splash’ impatiens (Impatiens walleriana), and ‘Score Red’ geranium (Pelargonium xhortorum) was similar for plants grown in GS-containing substrates and those grown in equivalent perlite- and PBH-containing substrates.

This book considers the so-called Unlikely Intersections, a topic that embraces well-known issues, such as Lang's and Manin-Mumford's, concerning torsion points in subvarieties of tori or abelian varieties. More generally, the book considers algebraic subgroups that meet a given subvariety in a set ofunlikelydimension. The book is an expansion of the Hermann Weyl Lectures delivered by Umberto Zannier at the Institute for Advanced Study in Princeton in May 2010. The book consists of four chapters and seven brief appendixes, the last six by David Masser. The first chapter considers multiplicative algebraic groups, presenting proofs of several developments, ranging from the origins to recent results, and discussing many applications and relations with other contexts. The second chapter considers an analogue in arithmetic and several applications of this. The third chapter introduces a new method for approaching some of these questions, and presents a detailed application of this (by Masser and the author) to a relative case of the Manin-Mumford issue. The fourth chapter focuses on the André-Oort conjecture (outlining work by Pila).