Osteopetrosis

Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer-term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal. It is anticipated that further understanding of the molecular pathogenesis of these conditions will reveal new targets for pharmacotherapy

An Individualized Approach to Cancer Screening Decisions in Older Adults: A Multilevel Framework

Guidelines for optimal cancer screening in older adults remain unclear, particularly for adults over the age of 75. While cancer screening in older adults may benefit some in good health, it may cause unnecessary burdens in others with limited life expectancy. Thus, a systematic approach to enable individualized cancer screening decisions in older adults is needed. We suggest a framework that guides such decisions through evidence-based approaches from multiple interactions, and that involves the patient, clinician, and healthcare system. An individualized approach considers differences in disease risk rather than the chronological age of the patient. This paper presents a comprehensive framework that depicts the independent and converging levels of influences on individualized cancer screening decisions in older adults. This Individualized Decisions for Screening (IDS) framework recognizes the reality of these interrelationships, including the tensions that arise when behaviors and outcomes are valued differently at the patient, clinician, and healthcare organization levels. Person-centered approaches are essential to advancing multilevel research of individualized cancer screening decisions among older adults

Differential effects of parental controls on adolescent substance use:for whom is the family most important?

Objective Social control theory assumes that the ability of social constraints to deter juvenile delinquency will be invariant across individuals. This paper tests this hypothesis and examines the degree to which there are differential effects of parental controls on adolescent substance use. Methods Analyses are based on self-reported data from 7,349 10th-grade students and rely on regression mixture models to identify latent classes of individuals who may vary in the effects of parental controls on drug use. Results All parental controls were significantly related to adolescent drug use, with higher levels of control associated with less drug use. The effects of instrumental parental controls (e.g., parental management strategies) on drug use were shown to vary across individuals, while expressive controls (e.g., parent/child attachment) had uniform effects in reducing drug use. Specifically, poor family management and more favorable parental attitudes regarding children’s drug use and delinquency had stronger effects on drug use for students who reported greater attachment to their neighborhoods, less acceptance of adolescent drug use by neighborhood residents, and fewer delinquent peers, compared to those with greater community and peer risk exposure. Parental influences were also stronger for Caucasian students versus those from other racial/ethnic groups, but no differences in effects were found based on students’ gender or commitment to school. Conclusions The findings demonstrate support for social control theory, and also help to refine and add precision to this perspective by identifying groups of individuals for whom parental controls are most influential. Further, they offer an innovative methodology that can be applied to any criminological theory to examine the complex forces that result in illegal behavior