My funky genetics : BRCA1/2 mutation carriers\u27 understanding of genetic inheritance and reproductive merger in the context of new reprogenetic technologies

Deleterious mutations in the BRCA1/BRCA2 genes elevate lifetime risk of breast and ovarian cancer. Each child of a mutation-positive parent has a 50% chance of inheriting it. Preimplantation genetic diagnosis (PGD) permits prospective parents to avoid the birth of a BRCA-mutation-positive child, introducing predictability into a process historically defined by chance. This investigation explored how BRCA1/2 mutation carriers understand genetic inheritance and consider a child\u27s inheritance of a BRCA1/2 mutation, given the opportunities that exist to pursue PGD. Thirty-nine female and male BRCA1/2 mutation carriers of reproductive age were recruited from urban cancer and reproductive medical centers. Participants completed a standardized educational presentation on PGD and prenatal diagnosis, with pre-and posttest assessments. An interdisciplinary team of qualitative researchers analyzed data using grounded theory techniques. Participants expressed the belief that reproduction yields children with unique genetic strengths and challenges, including the BRCA1/2 mutation, family traits for which predictive tests do not exist, and hypothetical genetic risks. Participants expressed preference for biologically related children, yet stated their genetically well partner\u27s lineage would be marred through reproductive merger, requiring the well partner to assume the burden of the BRCA1/2 mutation via their children. Participants expressed diverse views of genetically well partners\u27 participation in family planning and risk management decisions. Pressure to use reprogenetic technology may grow as genetic susceptibility testing becomes more widely available. Work with individuals and couples across the disease spectrum must be attuned to the ways beliefs about genetic inheritance play into reproductive decision-making. (PsycINFO Database Record (c) 2012 APA, all rights reserved) © 2012 American Psychological Association

Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States

Background: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods: We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of$1.0 B compared to PCV7. Conclusions: In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs

Effect of Student Involvement on Patient Perceptions of Ambulatory Care Visits

OBJECTIVE: To determine if patient satisfaction with ambulatory care visits differs when medical students participate in the visit. DESIGN: Randomized controlled trial. SETTING: Academic general internal medicine practice. PARTICIPANTS: Outpatients randomly assigned to see an attending physician only (N = 66) or an attending physician plus medical student (N = 68). MEASUREMENTS AND MAIN RESULTS: Patient perceptions of the office visit were determined by telephone survey. Overall office visit satisfaction was higher for the “attending physician only” group (61% vs 48% excellent), although this was not statistically significant (P = .16). There was no difference between the study groups for patient ratings of their physician overall (80% vs 85% excellent; P = .44). In subsidiary analyses, patients who rated their attending physician as “excellent” rated the overall office visit significantly higher in the “attending physician only” group (74% vs 55%; P = .04). Among patients in the “attending physician plus medical student” group, 40% indicated that medical student involvement “probably” or “definitely” did not improve their care, and 30% responded that they “probably” or “definitely” did not want to see a student at subsequent office visits. CONCLUSIONS: Although our sample size was small, we found no significant decrement in patient ratings of office visit satisfaction from medical student involvement in a global satisfaction survey. However, a significant number of patients expressed discontent with student involvement in the visit when asked directly. Global assessment of patient satisfaction may lack sensitivity for detection of dissatisfaction. Future research in this area should employ more sensitive measures of patient satisfaction

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Noise Probe of the Dynamic Phase Separation in La2/3Ca1/3MnO3

Giant Random Telegraph Noise (RTN) in the resistance fluctuation of a macroscopic film of perovskite-type manganese oxide La2/3Ca1/3MnO3 has been observed at various temperatures ranging from 4K to 170K, well below the Curie temperature (TC = 210K). The amplitudes of the two-level-fluctuations (TLF) vary from 0.01% to 0.2%. We use a statistical analysis of the life-times of the TLF to gain insight into the microscopic electronic and magnetic state of this manganite. At low temperature (below 30K) The TLF is well described by a thermally activated two-level model. An estimate of the energy difference between the two states is inferred. At higher temperature (between 60K and 170K) we observed critical effects of the temperature on the life-times of the TLF. We discuss this peculiar temperature dependence in terms of a sharp change in the free energy functional of the fluctuators. We attribute the origin of the RTN to be a dynamic mixed-phase percolative conduction process, where manganese clusters switch back and forth between two phases that differ in their conductivity and magnetization.Comment: 15 pages, PDF only, Phys. Rev. Lett. (in press

Mutations in \u3ci\u3eDMRT3\u3c/i\u3e Affect Locomotion in Horses and Spinal Circuit Function in Mice

Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favorable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation

Parents' perception of self-advocacy of children with myositis: an anonymous online survey

<p>Abstract</p> <p>Background</p> <p>Children with complex medical issues experience barriers to the transition of care from pediatric to adult providers. We sought to identify these barriers by elucidating the experiences of patients with idiopathic inflammatory muscle disorders.</p> <p>Methods</p> <p>We collected anonymous survey data using an online website. Patients and their families were solicited from the US and Canada through established clinics for children with idiopathic inflammatory muscle diseases as well as with the aid of a nonprofit organization for the benefit of such individuals. The parents of 45 older children/young adults suffering from idiopathic inflammatory muscle diseases were surveyed. As a basis of comparison, we similarly collected data from the parents of 207 younger children with inflammatory muscle diseases. The survey assessed transition of care issues confronting families of children and young adults with chronic juvenile myositis.</p> <p>Results</p> <p>Regardless of age of the patient, respondents were unlikely to have a designated health care provider assigned to aid in transition of care and were unlikely to be aware of a posted policy concerning transition of care at their pediatrician's office. Additionally, regardless of age, patients and their families were unlikely to have a written plan for moving to adult care.</p> <p>Conclusions</p> <p>We identified deficiencies in the health care experiences of families as pertain to knowledge, self-advocacy, policy, and vocational readiness. Moreover, as children with complex medical issues grow up, parents attribute less self-advocacy to their children's level of independence.</p

Economic Model of a Birth Cohort Screening Program for Hepatitis C Virus

Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus$53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus$39.8 billion); birth-cohort screening produces an incremental costeffectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus riskbased screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. Conclusion: Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-topay thresholds. (HEPATOLOGY 2012;55:1344-1355 H epatitis C virus (HCV) is the most common blood-borne viral infection in the United States, 1 affecting an estimated 3.6 million U.S. residents. 2 The majority of infected individuals develop chronic hepatitis; persistent liver injury leads to cirrhosis in 5$5 billion per year, 4 with projected HCV-related societal costs for the years 2010-2019 estimated to total $54.2 billion. 5 For the last decade, the standard of care for treating HCV has been the combination of pegylated interferon (Peg-IFN) and ribavirin (RBV), 6 which successfully eradicates virus (sustained virologic response; SVR) in 40%-80% of treated patients

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin