Living in the shadow of Lynch Syndrome: British women's accounts.

In this paper we explore accounts of eight British women living with Lynch Syndrome: a hereditary syndrome that increases the risk of developing bowel and gynecological cancers. We collected data via semi-structured interviews and analyzed them using Interpretative Phenomenological Analysis. Two themes, 'It's Up to Us': The Lynch Patient Experience; and 'The Biggest Challenge': The Lynch Parent Experience, illustrate the experiential burden and emotional labor of living with Lynch Syndrome. We theorize our analysis through Corbin and Strauss's concept of 'Health Work', and Hochschild's concept of 'Emotion Work'. Recommendations for clinical care and familial support are discussed.

A Normalized Congruent Matching Area Method for the Correlation of Breech Face Impression Images.

The congruent matching cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) for firearm evidence identification and error rate estimation. The CMC method divides the correlated image pairs into cells and uses four parameters to quantify topography similarity and pattern congruency of the correlated cell pairs in firearm breech face impressions on fired cartridge cases. A preliminary conservative numerical identification criterion of C = 6 CMCs was suggested for identifying images of cartridge cases fired from the same firearm. The CMC method was validated by correlations using both three-dimensional (3D) topography images and two-dimensional (2D) optical images from a set of 40 cartridge cases fired from a firearm set composed of 10 consecutively manufactured pistol slides. However, in the original CMC method, due to the difference in the effective data area of the correlated cells, final CMCs obtained from an image pair presented different data quantity (or validity level), and thus the empirical criterion C = 6 CMCs did not remain optimal for identification when the correlated cell size changed. In this study, a normalized congruent matching area (NCMA) method that considers the difference in the data area in each correlated cell pair was developed. Based on the NCMA method, an optimal range of cell sizes for breech face identification with granular characteristics was determined. A binomial model was used to fit the known nonmatching NCMA probability distribution Ψ NCMA, and a beta-binomial model was used to fit the known matching NCMA probability distribution Φ NCMA. An experimental improvement in the normalized identification criterion C of around 6 % was observed in the validation tests when the cell sizes were in the optimal range.

The Effect of Advance Directive Completion on Hospital Care Among Chronically Homeless Persons: a Prospective Cohort Study.

Advance care planning is relevant for homeless individuals because they experience high rates of morbidity and mortality. The impact of advance directive interventions on hospital care of homeless individuals has not been studied. The objective of this study was to determine if homeless individuals who complete an advance directive through a shelter-based intervention are more likely to have information from their advance directive documented and used during subsequent hospitalizations. The advance directive included preferences for life-sustaining treatments, resuscitation, and substitute decision maker(s). A total of 205 homeless men from a homeless shelter for men in Toronto, Canada, were enrolled in the study and offered an opportunity to complete an advance directive with the guidance of a trained counselor from April to June 2013. One hundred and three participants chose to complete an advance directive, and 102 participants chose to not complete an advance directive. Participants were provided copies of their advance directives. In addition, advance directives were electronically stored, and hospitals within a 1.0-mile radius of the shelter were provided access to the database. A prospective cohort study was performed using chart reviews to ascertain the documentation, availability, and use of advance directives, end-of-life care preferences, and medical treatments during hospitalizations over a 1-year follow-up period (April 2013 to June 2014) after the shelter-based advance directive intervention. Chart reviewers were blinded as to whether participants had completed an advance directive. The primary outcome was documentation or use of an advance directive during any hospitalization. The secondary outcome was documentation of end-of-life care preferences, without reference to an advance directive, during any hospitalization. After unblinding, charts were studied to determine whether advance directives were available, hospital care was consistent with patient preferences as documented in advance directives, and hospital resource utilization during admission. During the 1-year follow-up period, 38 participants who completed an advance directive and 37 participants who did not complete an advance directive had at least one hospitalization (36.9 vs. 36.2 %, p = 0.93). Participants who completed an advance directive were significantly more likely to have documentation or use of an advance directive in hospital, compared to participants who did not complete an advance directive (9.7 vs. 2.9 %, p = 0.047). Without reference to an advance directive, documentation of end-of-life care preferences occurred in 30.1 vs. 30.4 % of participants, respectively (p = 0.96), most often due to documentation of code status. There were no significant differences in resource utilization between admitted patients who completed and did not complete an advance directive. In conclusion, homeless men who complete an advance directive through a shelter-based intervention are more likely to have their detailed care preferences documented or used during subsequent hospitalizations.

Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.

Perceived barriers to success for resident physicians interested in immigrant and refugee health.

BACKGROUND: Cross-cultural care is recognized by the ACGME as an important aspect of US residency training. Resident physicians' preparedness to deliver cross-cultural care has been well studied, while preparedness to provide care specifically to immigrant and refugee populations has not been. METHODS: We administered a survey in October 2013 to 199 residents in Internal Medicine, Pediatrics, and Medicine/Pediatrics at the University of Minnesota, assessing perceived knowledge, attitudes, and experience with immigrant and refugee patients. RESULTS: Eighty-three of 199 residents enrolled in Internal Medicine, Pediatrics and Medicine/Pediatrics programs at the University of Minnesota completed the survey (42 %). Most (n = 68, 82 %) enjoyed caring for immigrants and refugees. 54 (65 %) planned to care for this population after residency, though 45 (54 %) were not comfortable with their knowledge regarding immigrant and refugee health. Specific challenges were language (n = 81, 98 %), cultural barriers (n = 76, 92 %), time constraints (n = 60, 72 %), and limited knowledge of tropical medicine (n = 57, 69 %). 67 (82 %) wanted more training in refugee and immigrant health. CONCLUSIONS: The majority of residents enjoyed caring for immigrant and refugee patients and planned to continue after residency. Despite favorable attitudes, residents identified many barriers to providing good care. Some involved cultural and language barriers, while others were structural. Finally, most respondents felt they needed more education, did not feel comfortable with their knowledge, and wanted more training during residency. These data suggest that residency programs consider increasing training in these specific areas of concern.

Medical Students' Views and Knowledge of the Affordable Care Act: A Survey of Eight U.S. Medical Schools.

BACKGROUND: It is not known whether medical students support the Affordable Care Act (ACA) or possess the knowledge or will to engage in its implementation as part of their professional obligations. OBJECTIVE: To characterize medical students' views and knowledge of the ACA and to assess correlates of these views. DESIGN: Cross-sectional email survey. PARTICIPANTS: All 5,340 medical students enrolled at eight geographically diverse U.S. medical schools (overall response rate 52% [2,761/5,340]). MAIN MEASURES: Level of agreement with four questions regarding views of the ACA and responses to nine knowledge-based questions. KEY RESULTS: The majority of respondents indicated an understanding of (75.3%) and support for (62.8%) the ACA and a professional obligation to assist with its implementation (56.1%). The mean knowledge score from nine knowledge-based questions was 6.9 ± 1.3. Students anticipating a surgical specialty or procedural specialty compared to those anticipating a medical specialty were less likely to support the legislation (OR = 0.6 [0.4-0.7], OR = 0.4 [0.3-0.6], respectively), less likely to indicate a professional obligation to implement the ACA (OR = 0.7 [0.6-0.9], OR = 0.7 [0.5-0.96], respectively), and more likely to have negative expectations (OR = 1.9 [1.5-2.6], OR = 2.3 [1.6-3.5], respectively). Moderates, liberals, and those with an above-average knowledge score were more likely to indicate support for the ACA (OR = 5.7 [4.1-7.9], OR = 35.1 [25.4-48.5], OR = 1.7 [1.4-2.1], respectively) and a professional obligation toward its implementation (OR = 1.9 [1.4-2.5], OR = 4.7 [3.6-6.0], OR = 1.2 [1.02-1.5], respectively). CONCLUSIONS: The majority of students in our sample support the ACA. Support was highest among students who anticipate a medical specialty, self-identify as political moderates or liberals, and have an above-average knowledge score. Support of the ACA by future physicians suggests that they are willing to engage with health care reform measures that increase access to care.

Chronically homeless persons' participation in an advance directive intervention: A cohort study.

BACKGROUND: Chronically homeless individuals have high rates of hospitalization and death, and they may benefit from the completion of advance directives. AIM: To determine the rate of advance directive completion using a counselor-guided intervention, identify characteristics associated with advance directive completion, and describe end-of-life care preferences in a group of chronically homeless individuals. DESIGN: Participants completed a survey and were offered an opportunity to complete an advance directive with a trained counselor. PARTICIPANTS: A total of 205 residents of a shelter in Canada for homeless men (89.1% of those approached) participated from April to June 2013. RESULTS: Duration of homelessness was ⩾12 months in 72.8% of participants, and 103 participants (50.2%) chose to complete an advance directive. Socio-demographic characteristics, health status, and health care use were not associated with completion of an advance directive. Participants were more likely to complete an advance directive if they reported thinking about death on a daily basis, believed that thinking about their friends and family was important, or reported knowing their wishes for end-of-life care but not having told anyone about these wishes. Among individuals who completed an advance directive, 61.2% named a substitute decision maker, and 94.1% expressed a preference to receive cardiopulmonary resuscitation in the event of a cardiorespiratory arrest if there was a chance of returning to their current state of health. CONCLUSION: A counselor-guided intervention can achieve a high rate of advance directive completion among chronically homeless persons. Most participants expressed a preference to receive cardiopulmonary resuscitation in the event of a cardiorespiratory arrest.

An Improved Algorithm of Congruent Matching Cells (CMC) Method for Firearm Evidence Identifications.

The Congruent Matching Cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) for firearm evidence identifications. The CMC method divides the measured image of a surface area, such as a breech face impression from a fired cartridge case, into small correlation cells and uses four identification parameters to identify correlated cell pairs originating from the same firearm. The CMC method was validated by identification tests using both 3D topography images and optical images captured from breech face impressions of 40 cartridge cases fired from a pistol with 10 consecutively manufactured slides. In this paper, we discuss the processing of the cell correlations and propose an improved algorithm of the CMC method which takes advantage of the cell correlations at a common initial phase angle and combines the forward and backward correlations to improve the identification capability. The improved algorithm is tested by 780 pairwise correlations using the same optical images and 3D topography images as the initial validation.

A Simple and Fast Spline Filtering Algorithm for Surface Metrology.

Spline filters and their corresponding robust filters are commonly used filters recommended in ISO (the International Organization for Standardization) standards for surface evaluation. Generally, these linear and non-linear spline filters, composed of symmetric, positive-definite matrices, are solved in an iterative fashion based on a Cholesky decomposition. They have been demonstrated to be relatively efficient, but complicated and inconvenient to implement. A new spline-filter algorithm is proposed by means of the discrete cosine transform or the discrete Fourier transform. The algorithm is conceptually simple and very convenient to implement.

Fired Cartridge Case Identification Using Optical Images and the Congruent Matching Cells (CMC) Method.

The Congruent Matching Cells (CMC) method for ballistics identification was invented at the National Institute of Standards and Technology (NIST). The CMC method is based on the correlation of pairs of small correlation cells instead of the correlation of entire images. Four identification parameters - T CCF, T θ, T x and T y are proposed for identifying correlated cell pairs originating from the same firearm. The correlation conclusion (matching or non-matching) is determined by whether the number of CMC is ≥ 6. This method has been previously validated using a set of 780 pair-wise 3D topography images. However, most ballistic images stored in current local and national databases are in an optical intensity (grayscale) format. As a result, the reliability of applying the CMC method on optical intensity images is an important issue. In this paper, optical intensity images of breech face impressions captured on the same set of 40 cartridge cases are correlated and analyzed for the validation test of CMC method using optical images. This includes correlations of 63 pairs of matching images and 717 pairs of non-matching images under top ring lighting. Tests of the method do not produce any false identification (false positive) or false exclusion (false negative) results, which support the CMC method and the proposed identification criterion, C = 6, for firearm breech face identifications using optical intensity images.

Cathepsin B is secreted apically from Xenopus 2F3 cells and cleaves the epithelial sodium channel (ENaC) to increase its activity.

The epithelial sodium channel (ENaC) plays an important role in regulating sodium balance, extracellular volume, and blood pressure. Evidence suggests the α and γ subunits of ENaC are cleaved during assembly before they are inserted into the apical membranes of epithelial cells, and maximal activity of ENaC depends on cleavage of the extracellular loops of α and γ subunits. Here, we report that Xenopus 2F3 cells apically express the cysteine protease cathepsin B, as indicated by two-dimensional gel electrophoresis and mass spectrometry analysis. Recombinant GST ENaC α, ß, and γ subunit fusion proteins were expressed in Escherichia coli and then purified and recovered from bacterial inclusion bodies. In vitro cleavage studies revealed the full-length ENaC α subunit fusion protein was cleaved by active cathepsin B but not the full-length ß or γ subunit fusion proteins. Both single channel patch clamp studies and short circuit current experiments show ENaC activity decreases with the application of a cathepsin B inhibitor directly onto the apical side of 2F3 cells. We suggest a role for the proteolytic cleavage of ENaC by cathepsin B, and we suggest two possible mechanisms by which cathepsin B could regulate ENaC. Cathepsin B may cleave ENaC extracellularly after being secreted or intracellularly, while ENaC is present in the Golgi or in recycling endosomes.

Rituximab inhibits Kv1.3 channels in human B lymphoma cells via activation of FcγRIIB receptors.

Kv1.3 channels play an important role in modulating lymphocyte proliferation and apoptosis. We hypothesized that Kv1.3 channels in B lymphocytes might be regulated by rituximab, an antibody to CD20, a drug for treatments of B-cell lymphomas and autoimmune diseases. Using both whole-cell and cell-attached patch-clamp techniques, we found that rituximab inhibited Kv1.3 channels in Daudi human B lymphoma cells by promoting the channel inactivation at a concentration which was much greater than that required for activation of CD20. The effect of rituximab on Kv1.3 channels was abolished after selective blockade of FcγRIIB receptors with anti-FcγRIIB antibody. Western blot experiments showed that Daudi B cells expressed both Kv1.3 channel and the low affinity Fc receptor, FcγRIIB, which could be activated by the Fc region of rituximab. In contrast, normal lymphocytes expressed less Kv1.3 channels with faster inactivation. Confocal microscopy and flow cytometry data showed that rituximab induced apoptosis of Daudi B cells and that the effect was attenuated by blockade of FcγRIIB receptors and partially mimicked by inhibition of Kv1.3 channels. These results suggest that in addition to previously described complement-dependent cytotoxicity, rituximab also induces apoptosis of malignant B lymphocyte by stimulating FcγRIIB receptors and inhibiting Kv1.3 channels.

Reporting likelihood ratio for casework in firearm evidence identification.

Likelihood ratio (LR) plays an important role in estimating the weight of evidence in firearm evidence identifications. LR is computed from a statistical model including the distribution of the known-matching (KM or within) and known-nonmatching (KNM or between) comparison scores. Current LR procedures rely on KM/KNM scores from existing reference firearm toolmark data sets or alternatively from generating a set of test fires using multiple firearms. Both procedures may contain theoretical or practical issues which may hinder the LR procedures from reporting an unbiased LR estimation in casework. In this paper, a reference data set was established from a set of firearms, each test-fired two cartridge cases, resulting in a basic data set and a control data set. The congruent matching cells (CMC) method was used to generate CMC scores that are used to fit in the KM/KNM statistical distributions for LR estimation. In the initial test, 130 firearms from eight manufacturers were used for generating a reference data set consisting of 260 cartridge cases representing 130 KM and 8385 KNM pairwise breech face images. Test results showed that the KM and KNM distribution intersect at CMC = 2, which is equivalent to LR = 1 (equally to support both the prosecutor and the defense propositions). When the CMC threshold is increased to 6 or more, the LR values are higher than a million, which can provide extremely strong support to the conclusion of the same firearm (or the prosecutor's proposition) in the casework of firearm evidence identification.

Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species.

Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (P(o)) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC P(o) and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde.

Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein.

Phosphatidylinositol phosphates (PIPs) are known to regulate epithelial sodium channels (ENaC). Lipid binding assays and coimmunoprecipitation showed that the amino-terminal domain of the ß- and γ-subunits of Xenopus ENaC can directly bind to phosphatidylinositol 4,5-bisphosphate (PIP(2)), phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), and phosphatidic acid (PA). Similar assays demonstrated various PIPs can bind strongly to a native myristoylated alanine-rich C-kinase substrate (MARCKS), but weakly or not at all to a mutant form of MARCKS. Confocal microscopy demonstrated colocalization between MARCKS and PIP(2). Confocal microscopy also showed that MARCKS redistributes from the apical membrane to the cytoplasm after PMA-induced MARCKS phosphorylation or ionomycin-induced intracellular calcium increases. Fluorescence resonance energy transfer studies revealed ENaC and MARCKS in close proximity in 2F3 cells when PKC activity and intracellular calcium concentrations are low. Transepithelial current measurements from Xenopus 2F3 cells treated with PMA and single-channel patch-clamp studies of Xenopus 2F3 cells treated with a PKC inhibitor altered Xenopus ENaC activity, which suggest an essential role for MARCKS in the regulation of Xenopus ENaC activity.

Virtual image standard (VIS) for performance evaluation of the congruent matching cells (CMC) algorithms in firearm evidence identifications.

The congruent matching cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) in 2012 for automatic and objective firearm evidence identifications and estimation of the weight of evidence in firearm evidence identifications. Since 2013, five CMC algorithms have been developed at NIST. In this paper, the virtual image standard (VIS) is proposed through trimming and stitching KNM images for quantitative performance evaluations of different CMC algorithms. The evaluation criteria include the correlation accuracy (both the CMC numbers and distribution pattern), correlation efficiency, false positive (FP) error rate, and the maximum separation of known matching (KM) and known non-matching (KNM) image pairs. The VIS composes correlation cells from different KNM images, which can provide a ground truth for verifying the CMC numbers, distribution patterns, and FP errors. By identifying three groups of VIS, the Convergence CMC algorithm showed superior performances for the future casework in firearm evidence identifications. Lastly, the success of this study suggests that the VIS could also be used to optimize the correlation parameters, to develop and test new CMC algorithms, and evaluate the performance before it is put into use for firearm examiner's casework.

A dysbiotic microbiome promotes head and neck squamous cell carcinoma.

Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.

Effect of an End-of-Life Planning Intervention on the completion of advance directives in homeless persons: a randomized trial.

BACKGROUND: Few interventions have focused on improving end-of-life care for underserved populations, such as homeless persons. OBJECTIVE: To determine whether homeless persons will complete a counseling session on advance care planning and fill out a legal advance directive designed to assess care preferences and preserve the dignity of marginalized persons. DESIGN: Prospective, single-blind, randomized trial comparing self-guided completion of an advance directive with professionally assisted advance care planning. (ClinicalTrials.gov registration number: NCT00546884) SETTING: 8 sites serving homeless persons in Minneapolis, Minnesota. PARTICIPANTS: 262 homeless persons recruited between November 2007 and August 2008. INTERVENTION: Minimal, self-guided intervention consisting of advance directive forms and written educational information versus a one-on-one advance planning intervention consisting of counseling and completing an advance directive with a social worker. MEASUREMENTS: Rate of advance directive completion, assessed by inspection of completed documents. RESULTS: The overall completion rate for advance directives was 26.7% (95% CI, 21.5% to 32.5%), with a higher rate in the counselor-guided group (37.9%) than in the self-guided group (12.8%) (CI of adjusted difference, 15.3 to 34.3 percentage points). This difference persisted across all sites and most subgroups. The advance directive's 4 clinical scenarios found a preference for surrogate decision making in 29% to 34% of written responses. LIMITATIONS: Sampling was limited to a more stable subset of the homeless population in Minneapolis and may have been subject to selection bias. Modest compensation to complete the preintervention survey could have influenced participants to complete advance directives. CONCLUSION: Both a simple and complex intervention successfully engaged a diverse sample of homeless persons in advance care planning. One-on-one assistance significantly increased the completion rate. Homeless persons can respond to an intervention to plan for end-of-life care and can express specific preferences for care or a surrogate decision maker, but additional studies are needed to assess the effect of these directives on subsequent care. PRIMARY FUNDING SOURCE: National Institute for Nursing Research and National Center on Minority Health and Health Disparities.