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This study had two aims. Aim one investigated achievement of 10 developmental milestones in children with Bardet-Biedl syndrome (BBS). Aim one data were derived from retrospective responses by caregivers of individuals with BBS who are enrolled in the Clinical Registry Investigating Bardet-Biedl syndrome (CRIBBS). CRIBBS is a natural history registry acquiring serial observations. Aim two investigated early adaptive skills using the Adaptive Behavior Assessment System (ABAS-II 0-5) completed by caregivers of children with BBS aged from 0 to 5. There were 652 individuals with milestone information (with some variability based on availability of information for specific milestones), and 101 individuals (including 95 among the 652) with ABAS-II information. Results revealed wide-ranging delays in adaptive skills, particularly in the domain of Self-Care. Expressive language appears to be the most frequently delayed developmental milestone. We found a difference by BBS genotype wherein individuals with BBS1 had higher adaptive/developmental scores than individuals with BBS10. Age also carried a significant association with adaptive skills diverging farther from a normative trajectory as children with BBS progress through early childhood., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

To develop luminescent molecular materials with predictable and stimuli-responsive emission, it is necessary to correlate changes in their geometries, packing structures, and noncovalent interactions with the associated changes in their optical properties. Here, we demonstrate that high-pressure single-crystal X-ray diffraction can be combined with high-pressure UV-visible absorption and fluorescence emission spectroscopies to elucidate how subtle changes in structure influence optical outputs. A piezochromic aggregation-induced emitter, sym -heptaphenylcycloheptatriene ( Ph 7 C 7 H ), displays bathochromic shifts in its absorption and emission spectra at high pressure. Parallel X-ray measurements identify the pressure-induced changes in specific phenyl-phenyl interactions responsible for the piezochromism. Pairs of phenyl rings from neighboring molecules approach the geometry of a stable benzene dimer, while conformational changes alter intramolecular phenyl-phenyl interactions correlated with a relaxed excited state. This tandem crystallographic and spectroscopic analysis provides insights into how subtle structural changes relate to the photophysical properties of Ph 7 C 7 H and could be applied to a library of similar compounds to provide general structure-property relationships in fluorescent organic molecules with rotor-like geometries.

The aim of this study was to explore kidney failure (KF) in Bardet-Biedl syndrome (BBS), focusing on high-risk gene variants, demographics, and morbidity. We employed the Clinical Registry Investigating BBS (CRIBBS) to identify 44 (7.2%) individuals with KF out of 607 subjects. Molecularly confirmed BBS was identified in 37 KF subjects and 364 CRIBBS registrants. KF was concomitant with recessive causal variants in 12 genes, with BBS10 the most predominant causal gene (26.6%), while disease penetrance was highest in SDCCAG8 (100%). Two truncating variants were present in 67.6% of KF cases. KF incidence was increased in genes not belonging to the BBSome or chaperonin-like genes (p < 0.001), including TTC21B, a new candidate BBS gene. Median age of KF was 12.5 years, with the vast majority of KF occurring by 30 years (86.3%). Females were disproportionately affected (77.3%). Diverse uropathies were identified, but were not more common in the KF group (p = 0.672). Kidney failure was evident in 11 of 15 (73.3%) deaths outside infancy. We conclude that KF poses a significant risk for premature morbidity in BBS. Risk factors for KF include female sex, truncating variants, and genes other than BBSome/chaperonin-like genes highlighting the value of comprehensive genetic investigation., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

The authors propose a holistic approach to life and living after the coronavirus crisis of 2020 has become history. Their method is to postulate studied reconsideration of the true needs of the human species, new know-how for all, novel codes of behavior, and drastic change to how we treat nature. Their findings name humanity's ballooning population as problem Number One. Without reverting to former ways, we need to apply our imagination to sound demographic principles, accept modest economic growth, and create much better stewardship of nature. Stated in terms of the futurist, a Great Acceleration should give way to a process we might call the Great Deceleration of humanity's tempo of life and mode of action. Readers are encouraged to eschew all thought of continuing with 'business as usual'. A purposeful limitation is the absence of all encouragement towards regrowth of wasteful manufacture and commerce. A systemic shift towards circular and green economies should be a key advance in all business revival. Another mode of being awaits; success of the encounter depends on humankind, not on theory., (© 2021 Durham University and John Wiley & Sons Ltd.)

Background: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that severely inhibits primary cilia function. BBS is typified by obesity in adulthood, but pediatric weight patterns, and thus optimal periods of intervention, are poorly understood., Objectives: To examine body mass differences by age, gender, and genotype in children and adolescents with BBS., Methods: We utilized the largest international registry of BBS phenotypes. Anthropometric and genetic data were obtained from medical records or participant/family interviews. Participants were stratified by age and sex categories. Genotype and obesity phenotype were investigated in a subset of participants with available data., Results: Height and weight measurements were available for 552 unique individuals with BBS. The majority of birth weights were in the normal range, but rates of overweight or obesity rapidly increased in early childhood, exceeding 90% after age 5. Weight z-scores in groups >2 years were above 2.0, while height z-scores approached 1.0, but were close to 0.0 in adolescents. Relative to those with the BBS10 genotype, the BBS1 cohort had a lower BMI z-score in the 2-5 and 6-11 age groups, with similar BMI z-scores thereafter. Children with biallelic loss of function (LOF) genetic variants had significantly higher BMI z-scores compared to missense variants., Conclusion: Despite normal birth weight, most individuals with BBS experience rapid weight gain in early childhood, with high rates of overweight/obesity sustained through adolescence. Children with LOF variants are disproportionally affected. Our findings support the need for earlier recognition and initiation of weight management therapies in BBS., (© 2020 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Despite possessing the desirable crystal packing and short PtPt stacking distances required for a large piezoresistive response, the conductivity-pressure response of the Magnus green salt [Pt(NH 3 ) 4 ][PtCl 4 ] is extremely sluggish. Through a combination of high-pressure X-ray diffraction and hybrid-DFT solid state calculations this study demonstrates that the poor conductivity-pressure response is due to a low volumetric compression anisotropy, a relatively large ambient pressure band gap and a lack of dispersion in the conduction band. Ligand modification (from NH 3 to NH 2 CH 3 ) does not enhance the piezoresistive response, causing even lower anisotropy of the volumetric compression and an unexpected phase transition at above 2 GPa. This study demonstrates that consideration of frontier band dispersion is a key design criterion, alongside crystal packing and PtPt stacking distances, for piezoresistive materials.

Bis(1,2-dionedioximato) complexes of Pt(ii) are known for their propensity to form linear chains of metal complexes in the solid state, and under the application of pressure members of the family display interesting optical and conductive properties. Two examples, Pt(bqd) 2 and Pt(dmg) 2 , are known to undergo insulator-to-metal-to-insulator transitions, with the metallic state reached at 0.8-1.4 GPa and 5 GPa, respectively. Previous interpretations of these materials' behaviour focused on the role of the filled d z 2 and vacant p orbitals on platinum, with little consideration to the role of the ligand. Here, the pressure-structural behaviour of Pt(bqd) 2 is investigated through single crystal X-ray diffraction, the first such study on this material. The difference in conductive behaviour under pressure between Pt(bqd) 2 and Pt(dmg) 2 is then interpreted through a combination of experimental and computational methods, including conductivity measurements under high pressure and electronic structure calculations. Our computational work reveals the significant contribution from ligand low-lying vacant π-orbitals to the frontier orbitals and bands in these complexes, and provides an explanation for the experimentally observed re-entrant insulator-to-metal-to-insulator transitions, and the differences in behaviour between the two compounds.

As of May 2017, there were 4242 Certified Genetic Counselors (CGC) (American Board of Genetic Counseling, Inc. 2017) and 41 graduate-level genetic counseling training programs (Accreditation Council for Genetic Counseling 2017) in North America, and the demand for CGCs continues to increase. In the Fall of 2015 the Genetic Counselor Workforce Working Group, comprised of representatives from the American Board of Genetic Counseling (ABGC), the Accreditation Council for Genetic Counseling (ACGC), the Association of Genetic Counseling Program Directors (AGCPD), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC) commissioned a formal workforce study to project supply of and demand for CGCs through 2026. The data indicate a shortage of genetic counselors engaged in direct patient care. Assuming two scenarios for demand, supply is expected to reach equilibrium between 2024 and 2030. However, given the rate of growth in genetic counseling training programs in the six months since the study was completed, it is reasonable to expect that the number of new programs may be higher than anticipated by 2026. If true, and assuming that growth in programs is matched by equivalent growth in clinical training slots, the supply of CGCs in direct patient care would meet demand earlier than these models predict.

This study investigated the differential contribution of affect and cognition to behavioral intention formation during pursuit of future health-related goals. Cognitive evaluations, affective evaluations and behavioral intentions were measured for each of 32 health-related behaviors. The timeframes of the cognitive/affective measures and the behavioral intention measure were varied between current and future timeframes creating four different conditions. Within-participants correlations between affect and intentions and cognition and intentions were calculated to determine the contribution of each factor to behavioral intention formation in the different timeframes. Results did not support the hypothesis that a shift from a reliance on affect to a reliance on cognition would occur as temporal distance increased. Within-participants analyses revealed a decrease in the contribution of cognition to behavioral intention formation when forming attitudes in the future condition.

Weapons of both defense and offense have grown steadily in their effectiveness--especially since the industrial revolution. The mass destruction of humanity, by parts or in whole, became reality with the advent of toxic agents founded on chemistry and biology or nuclear weapons derived from physics. The military's new non-combat roles, combined with a quest for non-lethal weapons, may change the picture in regard to conventional defense establishments but are unlikely to deter bellicose tyrants or the new terrorists from using the unlimited potential of today's and tomorrow's arsenals. The author addresses the issues that are raised by this developing situation with the intent of seeking those ethics that will enable us to survive in a future and uncertain world.

Researchers and technologists involved in the development of weapon systems can take their work to such extremes as to cause unplanned injury or death to others and lasting damage to the environment, reviewed here. In some cases innocent human casualties and ecological harm may actually be programmed and achieved. An analysis is proffered, attributing blame, and indicating efforts to correct the situation. The ethics involved are "complexified",a moral boundaries are exceeded, and humanity is transgressed as it develops solutions to the problem.

This paper investigates the relationship between sex status, community referral sources, and determination of voluntary or involuntary disposition. The relationship between sex status and involuntary disposition is made primarily through significant differences in community living arrangements associated with different referral sources. Males are more likely to be living in more institutional settings which are linked to more distant referral sources; females are more likely to remain in private living settings and to be referred by close sources. These differences in ecological location within the community are linked to disposition as voluntary treatment or involuntary detention. It is suggested that the criteria of reform legislation tightening procedures for involuntary disposition are more descriptive of the status of socially marginal and economically indigent males.