Fertility intentions following testing for a BRCA1 gene mutation

Journal ArticleObjective: To test whether fertility intentions differed among persons who tested positive, tested negative, or did not know their genetic status for a mutation of the BRCA1 gene. Method: Participants were members of a large Utah-based kindred with an identified mutation at the BRCA1 locus. Participants received genetic counseling prior to testing and were interviewed at baseline before testing and at three points after receiving test results from a genetic counselor. The sample included men and women who completed all interviews, were between ages 18 and 45, and were fertile, resulting in a sample of 101 respondents. The primary dependent variable measured whether a subject indicated that they were moderately or very sure at all three post-testing interviews that they intended to have additional children. Effects of BRCA1 mutation status on fertility intentions were estimated using multivariate logistic regressions where we controlled for gender, age, marital status, and baseline fertility intentions. Results: Female carriers were less likely to want additional children in relation to female noncarriers (odds ratio 0.12, 95% confidence interval 0.01-1.23; P = 0.074). No differences were found among men. There was a significant difference in the effect of mutation status on fertility intentions between males and females (Gender _x0001_ Carrier status interaction; P = 0.009). Persons who did not know their mutation status were less likely to want more children than noncarriers (odds ratio 0.09, 95% confidence interval 0.01-0.75; P = 0.027). Conclusion: Predictive genetic testing for late-onset cancer susceptibility affects family planning decision-making. Persons contemplating predictive testing should be informed about possible effects such testing may have on their plans for future fertility

Allied health manpower strategies: estimates of the potential gains from efficient task delegation

Journal ArticleThis study analyzes the potential impact of physician extenders on the productivity of primary care practices and considers the consequent implication for future health manpower requirements. A number of previous investigations have evaluated a variety of extenders in experimental settings. This study, in contrast, constructs and operates a simulation model of the representative practice permitting one to synthesize the experiences and insights of earlier demonstration projects. The model requires the practice to delegate tasks to paramedical personnel including the physician extender in such a way as to minimize the total cost of delivering a list of required medical services. The alternative acceptable techniques for delivering care are defined by the number of minutes of each type of medical personnel that must be employed in producing each service. Primary care is characterized by distinct medical services. The model reveals that physician extenders could increase the productivity of a representative primary care practice by up to 74 per cent. Alternatively, the commitment of physician time required to serve a patient load of 100 visits a week might be reduced by 14.2 hours through effective use of an extender. The article concludes with observations on the implications of physician extenders for future health manpower requirements

A population-based study of childhood cancer survivors body mass index

pre-printPopulation-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors. Procedure. Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis ( = 1060), and a comparison cohort selected on birth year and sex ( = 5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort. Results. Average time since diagnosis was 18.5 years (SD = 7.8), and mean age at BMI for both groups was 30.5 (survivors SD = 7.7, comparison SD = 8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR = 1.12, 95% CI 1.01-1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16-20 ( < 0.05). Conclusion. While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates

Interactive Effects of Physical Activity and APOE-ε4 On White Matter Tract Diffusivity in Healthy Elders

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer\u27s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffnesschondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process

Ultra-Deepwater Production Systems

The report herein is a summary of the work performed on three projects to demonstrate hydrocarbon drilling and production methods applicable to deep and ultra deepwater field developments in the Gulf of Mexico and other like applications around the world. This work advances technology that could lead to more economic development and exploitation of reserves in ultra-deep water or remote areas. The first project is Subsea Processing. Its scope includes a review of the ''state of the art'' in subsea components to enable primary production process functions such as first stage liquids and gas separation, flow boosting, chemical treatment, flow metering, etc. These components are then combined to allow for the elimination of costly surface production facilities at the well site. A number of studies were then performed on proposed field development projects to validate the economic potential of this technology. The second project involved the design and testing of a light weight production riser made of composite material. The proposed design was to meet an actual Gulf of Mexico deepwater development project. The various engineering and testing work is reviewed, including test results. The third project described in this report encompasses the development and testing of a close tolerance liner drilling system, a new technology aimed at reducing deepwater drilling costs. The design and prototype testing in a test well are described in detail

Additively Manufactured K-Band Septum Polarizers: A Comparative Study

A septum waveguide polarizer with integrated circular to square waveguide transition has been manufactured using three different additive manufacturing (AM) processes. Polymer and AlSi10Mg printing processes from a specialized RF manufacturer and a selective laser melting (SLM) process from a university research group are evaluated. Measurements confirm the polarizer design is well suited for AM

Ultra-Deepwater Production Systems

The report herein is a summary of the work performed on three projects to demonstrate hydrocarbon drilling and production methods applicable to deep and ultra deepwater field developments in the Gulf of Mexico and other like applications around the world. This work advances technology that could lead to more economic development and exploitation of reserves in ultra-deep water or remote areas. The first project is Subsea Processing. Its scope includes a review of the ''state of the art'' in subsea components to enable primary production process functions such as first stage liquids and gas separation, flow boosting, chemical treatment, flow metering, etc. These components are then combined to allow for the elimination of costly surface production facilities at the well site. A number of studies were then performed on proposed field development projects to validate the economic potential of this technology. The second project involved the design and testing of a light weight production riser made of composite material. The proposed design was to meet an actual Gulf of Mexico deepwater development project. The various engineering and testing work is reviewed, including test results. The third project described in this report encompasses the development and testing of a close tolerance liner drilling system, a new technology aimed at reducing deepwater drilling costs. The design and prototype testing in a test well are described in detail