Maternal and Paternal Risk Factors for Cryptorchidism and Hypospadias: A Case–Control Study in Newborn Boys

Little is known on environmental risk factors for cryptorchidism and hypospadias, which are among the most frequent congenital abnormalities. The aim of our study was to identify risk factors for cryptorchidism and hypospadias, with a focus on potential endocrine disruptors in parental diet and occupation. In a case–control study nested within a cohort of 8,698 male births, we compared 78 cryptorchidism cases and 56 hypospadias cases with 313 controls. The participation rate was 85% for cases and 68% for controls. Through interviews, information was collected on pregnancy aspects and personal characteristics, lifestyle, occupation, and dietary phytoestrogen intake of both parents. Occupational exposure to potential endocrine disruptors was classified based on self-reported exposure and ratings of occupational hygienists based on job descriptions. Our findings indicate that paternal pesticide exposure was associated with cryptorchidism [odds ratio (OR) = 3.8; 95% confidence interval (95% CI), 1.1–13.4]. Smoking of the father was associated with hypospadias (OR = 3.8; 95% CI, 1.8–8.2). Maternal occupational, dietary, and lifestyle exposures were not associated with either abnormality. Both abnormalities were associated with suboptimal maternal health, a lower maternal education, and a Turkish origin of the parents. Being small for gestational age was a risk factor for hypospadias, and preterm birth was a risk factor for cryptorchidism. Because paternal pesticide exposure was significantly associated with cryptorchidism and paternal smoking was associated with hypospadias in male offspring, paternal exposure should be included in further studies on cryptorchidism and hypospadias risk factors

Kinetics of cancer: a method to test hypotheses of genetic causation

BACKGROUND: Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR) genotypes and the kinetics of cancer progression. METHODS: Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age. RESULTS: The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p ˜ 0.008), with the same result for the association between mutation rate and the median age of onset. CONCLUSION: Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the acceleration of cancer. Our method of comparing genotypes provides good statistical tests even with small samples for each genotype

Dynein structure and power stroke

Dynein ATPases are microtubule motors that are critical to diverse processes such as vesicle transport and the beating of sperm tails; however, their mechanism of force generation is unknown. Each dynein comprises a head, from which a stalk and a stem emerge. Here we use electron microscopy and image processing to reveal new structural details of dynein c, an isoform from Chlamydomonas reinhardtii flagella, at the start and end of its power stroke. Both stem and stalk are flexible, and the stem connects to the head by means of a linker approximately 10 nm long that we propose lies across the head. With both ADP and vanadate bound, the stem and stalk emerge from the head 10 nm apart. However, without nucleotide they emerge much closer together owing to a change in linker orientation, and the coiled-coil stalk becomes stiffer. The net result is a shortening of the molecule coupled to an approximately 15-nm displacement of the tip of the stalk. These changes indicate a mechanism for the dynein power stroke

Hypothermia in a surgical intensive care unit

BACKGROUND: Inadvertent hypothermia is not uncommon in the immediate postoperative period and it is associated with impairment and abnormalities in various organs and systems that can lead to adverse outcomes. The aim of this study was to estimate the prevalence, the predictive factors and outcome of core hypothermia on admission to a surgical ICU. METHODS: All consecutive 185 adult patients who underwent scheduled or emergency noncardiac surgery admitted to a surgical ICU between April and July 2004 were admitted to the study. Tympanic membrane core temperature (Tc) was measured before surgery, on arrival at ICU and every two hours until 6 hours after admission. The following variables were also recorded: age, sex, body weight and height, ASA physical status, type of surgery, magnitude of surgical procedure, anesthesia technique, amount of intravenous fluids administered during anesthesia, use of temperature monitoring and warming techniques, duration of the anesthesia, ICU length of stay, hospital length of stay and SAPS II score. Patients were classified as either hypothermic (Tc ≤ 35°C) or normothermic (Tc> 35°C). Univariate analysis and multiple regression binary logistic with an odds ratio (OR) and its 95% Confidence Interval (95%CI) were used to compare the two groups of patients and assess the relationship between each clinical predictor and hypothermia. Outcome measured as ICU length of stay and mortality was also assessed. RESULTS: Prevalence of hypothermia on ICU admission was 57.8%. In univariate analysis temperature monitoring, use of warming techniques and higher previous body temperature were significant protective factors against core hypothermia. In this analysis independent predictors of hypothermia on admission to ICU were: magnitude of surgery, use of general anesthesia or combined epidural and general anesthesia, total intravenous crystalloids administrated and total packed erythrocytes administrated, anesthesia longer than 3 hours and SAPS II scores. In multiple logistic regression analysis significant predictors of hypothermia on admission to the ICU were magnitude of surgery (OR 3.9, 95% CI, 1.4–10.6, p = 0.008 for major surgery; OR 3.6, 95% CI, 1.5–9.0, p = 0.005 for medium surgery), intravenous administration of crystalloids (in litres) (OR 1.4, 95% CI, 1.1–1.7, p = 0.012) and SAPS score (OR 1.0, 95% CI 1.0–1.7, p = 0.014); higher previous temperature in ward was a significant protective factor (OR 0.3, 95% CI 0.1–0.7, p = 0.003). Hypothermia was neither a risk factor for hospital mortality nor a predictive factor for staying longer in ICU. CONCLUSION: The prevalence of patient hypothermia on ICU arrival was high. Hypothermia at time of admission to the ICU was not an independent factor for mortality or for staying longer in ICU

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

Parallel imaging: is GRAPPA a useful acquisition tool for MR imaging intended for volumetric brain analysis?

<p>Abstract</p> <p>Background</p> <p>The work presented here investigates parallel imaging applied to T1-weighted high resolution imaging for use in longitudinal volumetric clinical studies involving Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) patients. This was in an effort to shorten acquisition times to minimise the risk of motion artefacts caused by patient discomfort and disorientation. The principle question is, "Can parallel imaging be used to acquire images at 1.5 T of sufficient quality to allow volumetric analysis of patient brains?"</p> <p>Methods</p> <p>Optimisation studies were performed on a young healthy volunteer and the selected protocol (including the use of two different parallel imaging acceleration factors) was then tested on a cohort of 15 elderly volunteers including MCI and AD patients. In addition to automatic brain segmentation, hippocampus volumes were manually outlined and measured in all patients. The 15 patients were scanned on a second occasion approximately one week later using the same protocol and evaluated in the same manner to test repeatability of measurement using images acquired with the GRAPPA parallel imaging technique applied to the MPRAGE sequence.</p> <p>Results</p> <p>Intraclass correlation tests show that almost perfect agreement between repeated measurements of both segmented brain parenchyma fraction and regional measurement of hippocampi. The protocol is suitable for both global and regional volumetric measurement dementia patients.</p> <p>Conclusion</p> <p>In summary, these results indicate that parallel imaging can be used without detrimental effect to brain tissue segmentation and volumetric measurement and should be considered for both clinical and research studies where longitudinal measurements of brain tissue volumes are of interest.</p

Kondo physics in carbon nanotubes

The connection of electrical leads to wire-like molecules is a logical step in the development of molecular electronics, but also allows studies of fundamental physics. For example, metallic carbon nanotubes are quantum wires that have been found to act as one-dimensional quantum dots, Luttinger-liquids, proximity-induced superconductors and ballistic and diffusive one-dimensional metals. Here we report that electrically-contacted single-wall nanotubes can serve as powerful probes of Kondo physics, demonstrating the universality of the Kondo effect. Arising in the prototypical case from the interaction between a localized impurity magnetic moment and delocalized electrons in a metallic host, the Kondo effect has been used to explain enhanced low-temperature scattering from magnetic impurities in metals, and also occurs in transport through semiconductor quantum dots. The far higher tunability of dots (in our case, nanotubes) compared with atomic impurities renders new classes of Kondo-like effects accessible. Our nanotube devices differ from previous systems in which Kondo effects have been observed, in that they are one-dimensional quantum dots with three-dimensional metal (gold) reservoirs. This allows us to observe Kondo resonances for very large electron number (N) in the dot, and approaching the unitary limit (where the transmission reaches its maximum possible value). Moreover, we detect a previously unobserved Kondo effect, occurring for even values of N in a magnetic field.Comment: 7 pages, pdf onl

Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.Comment: 28 pages, 13 figure

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community

Development and evaluation of an open source software tool for deidentification of pathology reports

BACKGROUND: Electronic medical records, including pathology reports, are often used for research purposes. Currently, there are few programs freely available to remove identifiers while leaving the remainder of the pathology report text intact. Our goal was to produce an open source, Health Insurance Portability and Accountability Act (HIPAA) compliant, deidentification tool tailored for pathology reports. We designed a three-step process for removing potential identifiers. The first step is to look for identifiers known to be associated with the patient, such as name, medical record number, pathology accession number, etc. Next, a series of pattern matches look for predictable patterns likely to represent identifying data; such as dates, accession numbers and addresses as well as patient, institution and physician names. Finally, individual words are compared with a database of proper names and geographic locations. Pathology reports from three institutions were used to design and test the algorithms. The software was improved iteratively on training sets until it exhibited good performance. 1800 new pathology reports were then processed. Each report was reviewed manually before and after deidentification to catalog all identifiers and note those that were not removed. RESULTS: 1254 (69.7 %) of 1800 pathology reports contained identifiers in the body of the report. 3439 (98.3%) of 3499 unique identifiers in the test set were removed. Only 19 HIPAA-specified identifiers (mainly consult accession numbers and misspelled names) were missed. Of 41 non-HIPAA identifiers missed, the majority were partial institutional addresses and ages. Outside consultation case reports typically contain numerous identifiers and were the most challenging to deidentify comprehensively. There was variation in performance among reports from the three institutions, highlighting the need for site-specific customization, which is easily accomplished with our tool. CONCLUSION: We have demonstrated that it is possible to create an open-source deidentification program which performs well on free-text pathology reports