Citations

Recording body accelerations has been investigated previously to monitor health, metabolic energy expenditure, postural sway and falls [1]. Activity monitoring and the subsequent analysis of the accelerometry data have also proven useful in detecting physical activity levels among Parkinson’s [2] and osteoarthritis patients [3].

Gait analysis is an important tool in assessing the health and activity levels of patients and regular physical activity has been associated with health improvements in a number of populations. Step counting is one of the most commonly used measures of physical activity [1] and many studies have investigated the use of wearable sensors for step counts [2–4]. Their small size and light weight mean that they may be used in a free living environment and are suitable for home deployment. One of the main issues associated with step counts as a measure of physical activity is that a very high level of accuracy in step detection is needed.

We previously developed and validated a vortexing-sonication technique for detection of biofilm bacteria on the surface of explanted prosthetic joints. Herein, we evaluated this technique for diagnosis of infected breast tissue expanders and used it to assess colonization of breast tissue expanders. From April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders, six (85.7%) had positive cultures, one of which grewPropionibacteriumspecies. Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3–20.7%) without clinical evidence of infection also had positive cultures, 45 growingPropionibacteriumspecies and ten coagulase-negative staphylococci. While vortexing-sonication can detect clinically infected breast tissue expanders, 16 percent of breast tissue expanders appear to be asymptomatically colonized with normal skin flora, most commonly,Propionibacteriumspecies.

BACKGROUNDFluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests are commonly used to assess human epidermal growth factor 2 (HER2) status of tumors in patients with breast cancer. This analysis evaluates the likely cost‐effectiveness of expanded retesting to assess HER2 tumor status in women with early stage breast cancer.METHODSWe developed a decision‐analytic model to estimate the incremental cost‐effectiveness ratio (ICER) of expanded reflex testing from a US payer perspective. Expanded reflex testing is defined as retesting tumor specimens from patients whose tumors are IHC0, IHC1+, or FISH‐negative on their first test. In the base case, we assumed that 80% of patient tumors are initially IHC‐tested and 20% are FISH‐tested. Testing outcomes for IHC and FISH with and without retesting were based on published meta‐analyses. The cost of tests and treatment and the long‐term health outcomes were obtained from the literature.RESULTSIn the base case, we estimated that 2.27% of women who received expanded reflex testing would be HER2‐positive and receive trastuzumab treatment: the projected ICER was $36,721 per life year or $39,745 per quality‐adjusted life year (QALY). This varied between $47,100 per QALY and $35,500 per QALY if we assumed that 1%‐8% of patients retested were then HER2+, respectively. The results of deterministic and probabilistic sensitivity analysis were robust. This strategy would result in 4700 (2000‐17,000) patients being eligible to receive trastuzumab treatment annually.CONCLUSIONSRetesting patients who are IHC0, IHC1+, or FISH‐negative is projected to be a cost‐effective clinical strategy. Cancer 2013;119:3113–3122. © 2013 American Cancer Society.

Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.

ABSTRACT We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee ( n = 272) or hip ( n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture ( P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.

Abstract Background: Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants. Methods: We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci. Variants shared among all sequenced cases within each family were identified and filtered to exclude common variants and single-nucleotide variants (SNV) predicted to be benign. Results: We identified 32 nonsense or splice-site SNVs, 375 missense SNVs, 1,394 synonymous or noncoding SNVs, and 50 indels in the 16 families. Of particular interest are two validated and replicated missense variants in CENPE and KIF23, which are both located within previously reported CRC linkage regions, on chromosomes 1 and 15, respectively. Conclusions: Whole-exome sequencing identified DNA variants in multiple genes. Additional sequencing of these genes in additional samples will further elucidate the role of variants in these regions in CRC susceptibility. Impact: Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1239–51. ©2013 AACR.

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin ( sost ) gene was replaced by the β-D-galactosidase ( lacZ ) gene in the germ line. Knockout (KO) ( sost −/− ) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 ( cyp27B1 ) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.