The role of H-H interactions and impurities on the structure and energetics of H/Pd(111).

Understanding hydrogen incorporation into palladium requires detailed knowledge of surface and subsurface structure and atomic interactions as surface hydrogen is being embedded. Using density functional theory (DFT), we examine the energies of hydrogen layers of varying coverage adsorbed on Pd(111). We find that H-H and H-Pd interactions promote the formation of the well-known 3×3 phases but also favor an unreported (3 × 3) phase at high H coverages for which we present experimental evidence. We relate the stability of isolated H vacancies of the (3 × 3) phase to the need of H2 molecules to access bare Pd before they can dissociate. Following higher hydrogen dosage, we observe initial steps of hydride formation, starting with small clusters of subsurface hydrogen. The interaction between H and Pd is complicated by the persistent presence of carbon at the surface. X-ray photoelectron spectroscopy experiments show that trace amounts of carbon, emerging from the Pd bulk despite many surface cleaning cycles, become mobile enough to repopulate the C-depleted surface at temperatures above 200 K. When exposed to hydrogen, these surface carbon atoms react to form benzene, as evidenced by scanning tunneling microscopy observations interpreted with DFT.

Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches.

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.

Integrative molecular profiling of routine clinical prostate cancer specimens.

BACKGROUND: Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. PATIENTS AND METHODS: We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. RESULTS: We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. CONCLUSIONS: Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.

'One Health' investigation: outbreak of human Salmonella Braenderup infections traced to a mail-order hatchery - United States, 2012-2013.

Human salmonellosis linked to contact with live poultry is an increasing public health concern. In 2012, eight unrelated outbreaks of human salmonellosis linked to live poultry contact resulted in 517 illnesses. In July 2012, PulseNet, a national molecular surveillance network, reported a multistate cluster of a rare strain of Salmonella Braenderup infections which we investigated. We defined a case as infection with the outbreak strain, determined by pulsed-field gel electrophoresis, with illness onset from 25 July 2012-27 February 2013. Ill persons and mail-order hatchery (MOH) owners were interviewed using standardized questionnaires. Traceback and environmental investigations were conducted. We identified 48 cases in 24 states. Twenty-six (81%) of 32 ill persons reported live poultry contact in the week before illness; case-patients named 12 different MOHs from eight states. The investigation identified hatchery D as the ultimate poultry source. Sampling at hatchery D yielded the outbreak strain. Hatchery D improved sanitation procedures and pest control; subsequent sampling failed to yield Salmonella. This outbreak highlights the interconnectedness of humans, animals, and the environment and the importance of industry knowledge and involvement in solving complex outbreaks. Preventing these infections requires a 'One Health' approach that leverages expertise in human, animal, and environmental health.

Empowerment among Latina nurses in Mexico, New York and Indiana.

BACKGROUND: Increasing empowerment among nurses may help retain nurses and increase the international workforce. There are very few cross-national studies of nurse empowerment reported in the professional literature. AIM: To conduct a cross-national exploratory study testing a theoretical model of nurse empowerment. DESIGN: Descriptive survey of three convenience samples of graduate Latina nurses in Monterrey, Mexico, New York City and Indiana. METHODS: Data were collected using self-administered questionnaires. The Klakovich Reciprocal Empowerment Scale (RES) was translated into Mexican-Spanish using a translation back-translation technique. Variables for the study included empowerment, years of experience, job satisfaction and intent to stay. Frequency distributions and descriptive statistics were used to analyse the data. FINDINGS: Empowerment involves reciprocity between the leader and follower, a common vision and synergy about the work, and a sense of ownership in the work site. Mexican nurses scored significantly higher on synergy than Latina nurses in New York and Indiana. Empowerment is related to job satisfaction, age and years of employment. CONCLUSIONS: Results indicate the usefulness of the RES instrument for Latina nurses and the need for further research with larger samples. Cross-national research provides culturally sensitive information. Such research partnerships facilitate modelling the importance of nursing research to graduate nurses and students.

TCDD-inducible poly(ADP-ribose) polymerase: a novel response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes pleotropic effects in mammalian species through modulating gene expression. Here we analyzed TCDD-induced mRNA expression by using mRNA differential display and report the cloning of a novel TCDD-inducible poly(ADP-ribose) polymerase (TiPARP). TiPARP cDNA contains an open reading frame of 657 amino acid residues; the carboxyl half shares sequence similarity to the catalytic domain of PARP, a family of enzymes that catalyze poly ADP-ribosylation of proteins. Expression of the cDNA by in vitro transcription/translation reveals a protein of approximately 75 kDa. The expressed TiPARP exhibits PARP activity toward histone. TiPARP is highly homologous to RM1 which is induced during long-term potentiation, a memory formation process, and to TIL which is induced in T cells infiltrating progressing tumors. TiPARP mRNA is expressed in a broad range of mouse tissues. Together, these data demonstrate that TiPARP is a novel target of TCDD that may contribute to multiple responses to TCDD by modulating protein function through poly ADP-ribosylation.

A new tool for predicting erectile dysfunction.

The Sexual Health Inventory for Men (SHIM) is an effective way to assess erectile difficulty (ED). Despite documented efficacy, however, many physicians may be reluctant to incorporate it into clinical practice because of the intimate nature of the questionnaire. In an attempt to devise and test an easy-to-use computer-based SHIM score indicator for office use, more than 30,000 SHIM questionnaires were administered to men visiting physicians' offices in 2000. Information about age, current smoking status, diabetes, depression, hypertension, prostate disease, and cholesterol levels was also collected. A logistic regression model with a sensitivity of 81.8% and a specificity of 57.7% was created to predict the likelihood of ED in a patient scoring below 21 (SHIM definition). This model was built into a highly graphic Windows-based program. The SHIM score indicator is a convenient way to rapidly identify patients at high risk for ED who should be further assessed.

Epsin 3 is a novel extracellular matrix-induced transcript specific to wounded epithelia.

Using an in vitro model of keratinocyte activation by the extracellular matrix following injury, we have identified epsin 3, a novel protein closely related to, but distinct from previously described epsins. Epsin 3 contains a domain structure common to this gene family, yet demonstrates novel differences in its regulation and pattern of expression. Epsin 3 mRNA and protein were undetectable in keratinocytes isolated from unwounded skin, but induced in cells following contact with fibrillar type I collagen. The native triple helical structure of collagen was required to mediate this response as cells failed to express epsin 3 when plated on gelatin. Consistent with the reported function of other epsins, epsin 3 was evident in keratinocytes as punctate vesicles throughout the cytoplasm that partially co-localized with clathrin. In addition, epsin 3 exhibited nuclear accumulation when nuclear export was inhibited. In contrast to other known epsins, epsin 3 was restricted to keratinocytes migrating across collagen and down-regulated following cell differentiation, suggesting that expression was spatially and temporally regulated. Indeed, epsin 3 was localized specifically to migrating keratinocytes in cutaneous wounds, but not found in intact skin. Intriguingly, Northern hybridization and reverse transcriptase-polymerase chain reaction experiments indicated that epsin 3 expression was restricted to epithelial wounds or pathologies exhibiting altered cell-extracellular matrix interactions. Thus, we have identified a novel type I collagen-induced epsin that demonstrates structural and behavioral similarity to this gene family, yet exhibits restricted and regulated expression, suggesting that epsin 3 may serve an important function in activated epithelial cells during tissue morphogenesis.

A new look at nurse burnout: the effects of environmental uncertainty and social climate.

As healthcare organizations deal with changes in the external environment, uncertainty in the internal environment is created. The purpose of this study was to explore the relationships among environmental uncertainty, social climate, and burnout among staff nurses. Multiple regression analysis was used to explore relationships among study variables. Perceived environmental uncertainty predicted burnout among staff nurses, although there was no significant relationship between burnout and objective measures of unit activity. The social climate of the workplace was negatively associated with burnout. The authors concluded that social networks are important during times of change and uncertainty in the work environment; in other words, a supportive workplace can protect against burnout.

The Missing Link: Early Methane ("T") Dwarfs in the Sloan Digital Sky Survey.

We report the discovery of three cool brown dwarfs that fall in the effective temperature gap between the latest L dwarfs currently known, with no methane absorption bands in the 1-2.5 µm range, and the previously known methane (T) dwarfs, whose spectra are dominated by methane and water. The newly discovered objects were detected as very red objects in the Sloan Digital Sky Survey imaging data and have JHK colors between the red L dwarfs and the blue Gl 229B-like T dwarfs. They show both CO and CH(4) absorption in their near-infrared spectra in addition to H(2)O, with weaker CH(4) absorption features in the H and K bands than those in all other methane dwarfs reported to date. Due to the presence of CH(4) in these bands, we propose that these objects are early T dwarfs. The three form part of the brown dwarf spectral sequence and fill in the large gap in the overall spectral sequence from the hottest main-sequence stars to the coolest methane dwarfs currently known.

Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice.

Shiga toxin-producing Escherichia coli (STEC) cause significant disease; treatment is supportive and antibiotic use is controversial. Ciprofloxacin but not fosfomycin causes Shiga toxin-encoding bacteriophage induction and enhanced Shiga toxin (Stx) production from E. coli O157:H7 in vitro. The potential clinical relevance of this was examined in mice colonized with E. coli O157:H7 and given either ciprofloxacin or fosfomycin. Both antibiotics caused a reduction in fecal STEC. However, animals treated with ciprofloxacin had a marked increase in free fecal Stx, associated with death in two-thirds of the mice, whereas fosfomycin did not. Experiments that used a kanamycin-marked Stx2 prophage demonstrated that ciprofloxacin, but not fosfomycin, caused enhanced intraintestinal transfer of Stx2 prophage from one E. coli to another. These observations suggest that treatment of human STEC infection with bacteriophage-inducing antibiotics, such as fluoroquinolones, may have significant adverse clinical consequences and that fluoroquinolone antibiotics may enhance the movement of virulence factors in vivo.

Sense of belonging and new graduate job satisfaction.

This study investigated the relationship between sense of belonging and job satisfaction in the new graduate RN. Ninety-five new graduate RNs answered a survey about demographic information and work setting, as well as their satisfaction and sense of belonging in the work environment. McCloskey-Mueller's Satisfaction Scale and a modified version of the Hagerty-Patusky Sense of Belonging Instrument were used. The conceptual framework was derived from Marlene Kramer's work on Reality Shock (1974). Results showed new graduates were most satisfied with coworkers and least satisfied with professional opportunities for advancement. Sense of belonging and total satisfaction were highest in the home healthcare setting. A Pearson r was used to determine relationships between sense of belonging, total satisfaction, and satisfaction sub-scales. Sense of belonging had significant positive relationships with total satisfaction, interaction opportunities, praise, control, coworkers, and scheduling. Possible future research suggested examining how orientation and work group numbers may affect job satisfaction and sense of belonging.

Assessing the feasibility of a clinical practice guideline for inpatient smoking cessation intervention.

Although a great deal of effort has been devoted to the development of evidence-based practice guidelines at both the national and local levels, relatively few studies have explored translating these guidelines into clinical practice. The purpose of this study was to assess the feasibility of implementing an inpatient smoking cessation intervention, based on an externally developed clinical practice guideline, at a tertiary care medical center. All smokers who were referred to cardiac rehabilitation services for a 5-week period were eligible for referral to the smoking cessation program. Twenty patients participated in the bedside counseling program. The mean amount of time to deliver the intervention was 43.5 minutes. At 1 month, 14 (70%) of the participants reported continuous abstinence from tobacco. Estimated cost per patient for smoking cessation intervention was $51.14.

Chart reminders increase referrals for inpatient smoking cessation intervention.

The purpose of this study was to test the effect of a chart reminder system on referral of inpatients to a hospital smoking cessation intervention pilot program. An A1-B-A2 reversal design was used to test the hypothesis that a chart reminder to nursing staff would increase the proportion of smokers referred for smoking cessation intervention over the usual method of posted memos. In Condition A1, memos reminding nursing staff to refer smokers were posted prominently on a cardiopulmonary unit for 4 weeks. In Condition B, a reminder containing the same message was placed in the front of every patient chart for 4 weeks. Finally, in Condition A2, chart reminders were removed and posted memos were reinstated for 4 additional weeks. During Condition A1 (posted memo), only one patient out of 29 eligible smokers was referred, for a referral rate of 3.4%. In Condition B (chart reminders), 18 patients out of 52 (34.6%) were referred (chi 2 = 10.07, p < 0.01). In Condition A2, the referral rate returned to below baseline (2.1%) (chi 2 = 16.80, p < 0.001). The findings support the use of a chart reminder system for screening and referral as an important component for comprehensive smoking cessation programs in the acute care setting.

Computer use in staff development. A national survey.

The Informatics Task Force of the National Nursing Staff Development Organization (NNSDO) conducted a national survey soliciting information about computer use in staff development. More than 600 members responded to the survey, suggesting that informatics and the issues surrounding nurses' use of computers are of concern to many staff development professionals. Responses from focus groups held at the National Nursing Staff Development Organization annual convention provided additional input. The results of the survey and discussion sessions have implications for preparing nurse educators for the specialty practice of staff development in the future.

Health status and mammography use among older women.

OBJECTIVE: To assess the extent to which an age-associated reduction in mammography use can be explained by declining self-reported health status. DESIGN: We analyzed data from the 1992 National Health Interview Survey (NHIS) and Cancer Control Supplement. Logistic regression analysis was used to evaluate the association between age, health status (self-reported health and limitations in major activity), and other variables potentially related to mammography use within the past 1 year (recent mammography). PARTICIPANTS: Of 12,035 NHIS respondents we restricted our analysis to the 1,772 women aged 50 years or older who reported one or more lifetime mammograms. We excluded women without a mammogram (n = 937) because we were interested in factors related to recent use versus past use of mammography. MEASUREMENTS AND MAIN RESULTS: The percentage of women with a recent mammogram declined with increasing age, and the age association was independent of other factors including health status (adjusted odds ratio [OR] comparing women aged 75 years or older with those aged 50 to 64 years was 0.54; 95% confidence interval [CI] 0.41, 0.70). This age effect persisted in an analysis restricted to women reporting good or better health (adjusted OR was 0.60, 95% CI 0.44, 0.80). CONCLUSION: The observed decline in recent mammography use with advancing age was not explained by variation in health status. Because healthy elderly women may live long enough to realize the potential benefit of screening mammography, factors responsible for its reduced use should be identified. Doing so will allow for the selective promotion of screening mammography among those older women most likely to benefit.

Development of dynorphin-like immunoreactive auditory nerve terminals in the chick.

The novel discovery that auditory nerve terminals in the chick cochlear nucleus magnocellularis (NM) are immunoreactive for the opioid peptide dynorphin (DYN) was recently reported [3]. The present study examines the development of DYN-immunoreactivity (DYN-I) in auditory nerve terminals in NM from embryos through young post-hatch chicks. No DYN-I was observed in NM at embryonic day 13 (E13). DYN-I first appeared at E16 as short flat structures partially surrounding NM cell bodies. Around post-hatch day 1 (P1), these structures had a more rounded, chalice-type of morphology reminiscent of the specialized auditory nerve terminals found in birds, the end-bulbs of Held. At P6, most NM neurons were circumscribed by a prominent DYN-I calyceal-type of ending. By P13, fewer NM cells were ringed by this DYN-I and by the third post-hatch week, there was very little DYN-I in NM. There were no obvious differences in the density of DYN-I terminals across either the rostrocaudal length or the mediolateral width of NM at any age examined. These results suggest that during a restricted time of development, end-bulbs of Held in the chick NM contain DYN.

Developing and testing a prototype patients care database.

The purpose of the two pilot studies described in this article was to develop and evaluate a database for managing patient care information. A retrospective review of medical records for 67 patients was used for capturing nursing information. Three categories of data were obtained: (1) patient problems, (2) nursing interventions, and (3) patient outcome achievement. A total of 439 patient problems was identified. A total of 4541 discrete nursing interventions were coded, with assessment and surveillance activities accounting for 26% of the total. The degree to which targeted patient outcomes were achieved was assessed by analyzing documentation of patient outcomes in the medical record. Of 2326 expected patient outcomes identified, only 55% (1272) were documented as "met" in the medical records. Potential uses for the database include outlier analysis and outcomes assessment in specific patient populations.