Introduction of alvimopan into an enhanced recovery protocol for colectomy offers benefit in open but not laparoscopic colectomy.
Alvimopan coupled with an enhanced recovery protocol (ERP) has been shown to reduce length of stay (LOS) after open colectomy, but its role after laparoscopy remains unknown. This study evaluated alvimopan with an established ERP for laparoscopic (LAP), hand-assisted laparoscopic (HAL), and open colectomy. Consecutive patients who underwent elective colectomy by any technique were retrospectively identified. Patients were excluded if they developed a major intra-abdominal complication, medical complication, or had a complex preoperative evaluation. Patients were stratified into 4 groups based on the surgical approach (open/HAL vs. LAP) and the use of alvimopan. All patients were managed by using an ERP. The incidence of postoperative ileus (POI) and LOS were compared between alvimopan and control groups for each surgical approach. There were 282 patients. Demographics were similar across the 4 groups. The mean number of alvimopan doses administered was 6.7±2.6. For patients in the open/HAL group (n=149), the incidence of primary ileus was 9.5% (7/74) and 16% (12/75) for alvimopan and control patients, respectively (P=.231). A significant decrease in LOS was noted with alvimopan (5.6±2.5 vs. 6.8±3.3 days, P=.009). For patients after LAP (n=133), there was no significance difference in POI with or without alvimopan (3.9% [3/76] vs. 3.5% [2/57], P=1.00). There was no difference in LOS (3.9±1 vs. 3.7±1.4 days, P=.305). The addition of alvimopan to an established ERP will lead to improvement in clinical outcomes in patients after open/HAL colectomy. The benefit of alvimopan after LAP remains negligible.


Effective dose efficiency: an application-specific metric of quality and dose for digital radiography.
The detective quantum efficiency (DQE) and the effective DQE (eDQE) are relevant metrics of image quality for digital radiography detectors and systems, respectively. The current study further extends the eDQE methodology to technique optimization using a new metric of the effective dose efficiency (eDE), reflecting both the image quality as well as the effective dose (ED) attributes of the imaging system. Using phantoms representing pediatric, adult and large adult body habitus, image quality measurements were made at 80, 100, 120 and 140 kVp using the standard eDQE protocol and exposures. ED was computed using Monte Carlo methods. The eDE was then computed as a ratio of image quality to ED for each of the phantom/spectral conditions. The eDQE and eDE results showed the same trends across tube potential with 80 kVp yielding the highest values and 120 kVp yielding the lowest. The eDE results for the pediatric phantom were markedly lower than the results for the adult phantom at spatial frequencies lower than 1.2-1.7 mm(-1), primarily due to a correspondingly higher value of ED per entrance exposure. The relative performance for the adult and large adult phantoms was generally comparable but affected by kVps. The eDE results for the large adult configuration were lower than the eDE results for the adult phantom, across all spatial frequencies (120 and 140 kVp) and at spatial frequencies greater than 1.0 mm(-1) (80 and 100 kVp). Demonstrated for chest radiography, the eDE shows promise as an application-specific metric of imaging performance, reflective of body habitus and radiographic technique, with utility for radiography protocol assessment and optimization.


Interaction of proteins with promoter elements of the human U2 snRNA genes in vivo.
The multicopy human U2 small nuclear (sn)RNA genes are transcribed by RNA polymerase (pol) II and contain two major promoter elements upstream of the transcription start site: an essential proximal sequence element (PSE) at around -55 and a distal sequence element (DSE) at around -220. We have carried out an in vivo footprinting analysis on these genes, and the results suggest that most, if not all, of the U2 gene promoters are bound by factors in interphase. Both the DSE and the PSE are protected from digestion, and the pattern of methylation protection over the DSE is virtually identical to that obtained in vitro using nuclear extract. Our results also indicate that the DNA between the PSE and the transcription start site is distorted and that proteins interact with the promoter between -20 and -33. Mutation of this sequence affects both the accuracy of initiation and polymerase specificity, underlining the importance of this region in U2 gene expression. We have also analysed the pattern of protection over the DSE and PSE of the U2 genes in mitotic cells. The degree of protection over all promoter elements is drastically reduced, suggesting that loss of DNA binding factors from the promoter plays a role in the shutdown of U2 gene transcription in mitosis.


The open access advantage.
A study published today in PLoS Biology provides robust evidence that open-access articles are more immediately recognized and cited than non-OA articles. This editorial provides some additional follow up data from the most recent analysis of the same cohort in April 2006, 17 to 21 months after publication. These data suggest that the citation gap between open access and non-open access papers continues to widen. I conclude with the observation that the "open access advantage" has at least three components: (1) a citation count advantage (as a metric for knowledge uptake within the scientific community), (2) an end user uptake advantage, and (3) a cross-discipline fertilization advantage. More research is needed, and JMIR is inviting research on all aspects of open access. As the advantages for publishing open access from a researchers' point of view become increasingly clear, questions around the sustainability of open access journals remain. This journal is a living example that "lean publishing" models can create successful open access journals. Open source tools which have been developed by the Public Knowledge Project at the University of British Columbia with contributions from the Epublishing & Open Access group at the Centre for Global eHealth Innovation in Toronto are an alternative to hosting journals on commercial open access publisher sites.


Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known. Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively. BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs. Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.


One-dimensional daisyworld: spatial interactions and pattern formation.
The zero-dimensional daisyworld model of Watson and Lovelock (1983) demonstrates that life can unconsciously regulate a global environment. Here that model is extended to one dimension, incorporating a distribution of incoming solar radiation and diffusion of heat consistent with a spherical planet. Global regulatory properties of the original model are retained. The daisy populations are initially restricted to hospitable regions of the surface but exert both global and local feedback to increase this habitable area, eventually colonizing the whole surface. The introduction of heat diffusion destabilizes the coexistence equilibrium of the two daisy types. In response, a striped pattern consisting of blocks of all black or all white daisies emerges. There are two mechanisms behind this pattern formation. Both are connected to the stability of the system and an overview of the mathematics involved is presented. Numerical experiments show that this pattern is globally determined. Perturbations in one region have an impact over the whole surface but the regulatory properties of the system are not compromised by transient perturbations. The relevance of these results to the Earth and the wider climate modelling field is discussed.


Institutionalizing interprofessional education in small states: perspectives from faculty and key stakeholders in Malta.
The benefits of a collaborative practice-ready workforce for patient-centered care are internationally gaining momentum and the Interprofessional education (IPE) movement is contributing to this. In the small island state of Malta, the importance of a collaborative health-care workforce is being promoted and endorsed in policy documents. However, IPE has not yet been formally integrated into professional health education curricula. This qualitative case study aimed to explore stakeholders' perspectives and perceptions of a possible IPE initiative at the Faculty of Health Sciences, University of Malta. A purposive sampling method with 59 participants including academics and senior policy-makers was used. Data were gathered through focus groups, one-to-one interviews and documentary searches and analyzed using a 'Framework' approach supported by NVivo 10. Four major themes were identified encompassing enablers and barriers for IPE: a) IPE could be beneficial, b) institutional and organizational barriers, c) professional barriers, and d) cultural barriers. This study highlights a range of interdependent challenges in the implementation of IPE from the perspective of the small state of Malta that can nonetheless contribute insights for other smaller sized nations for the development and formalization of collaborative innovations in the educational curricula of health professionals. In particular, it highlights that national cultural dimensions or traits may represent a relatively unexplored barrier to date for the successful implementation of IPE in specific countries.


Extraperitoneal Laparoscopic Radical Nephroureterectomy and Lymph Node Dissection in Modified Supine Position.
To explore the feasibility of extraperitoneal laparoscopic radical nephroureterectomy (EL-RNU) and lymph node dissection in a modified supine position for managing urothelial carcinomas in the renal pelvis or in the upper two-thirds of the ureter. Consecutively from January 2014 to October 2015, 15 patients with high-risk urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter underwent EL-RNU and extraperitoneal laparoscopic lymph node dissection (EL-LND). Clinical and pathologic data, histologic nodal status, perioperative complications, and recurrence data were collected. All of the 15 patients were treated with EL-RNU and EL-LND in a modified supine position, and none was converted to open surgery. The mean operation time was 178 ± 18 minutes. The mean estimated blood loss was 140 ± 40 mL. The mean postoperative intestinal function recovery time was 2 days. The mean postoperative hospitalization was 7 ± 1 days. Pathologic studies revealed positive lymph nodes in 3 patients (20%). The mean number of harvested lymph nodes was 12 ± 3. No local recurrence and distant metastasis were found after a median follow-up of 14.4 months (7-23 months). EL-RNU and EL-LND in the modified supine position are mini-invasive and feasible for patients with urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter. Good exposure and dissection of the abdominal aorta and inferior vena cava and the integrity of the peritoneum are key to the operational success of this approach.


Internalized racism's association with African American male youth's propensity for violence.
Youth violence in African American communities is still considered to be at epidemic proportions. The traditional risk factors for youth violence (i.e. delinquent friends, poverty, drug use, carrying a weapon etc.) do not account for the disproportionate overrepresentation of African American males. This study sought to better understand the propensity for violence among African American males ages 14-19 years (N=224) from four different programmatic sites: a Philadelphia high school, an African-centered charter high school, a youth detention facility, and a program that serves youth who are on probation or parole. The findings indicate that internalized racism enhances the variance explained above the variables typically explored in the delinquency and criminology literature. If further research can replicate these findings, this has implications for the content and direction of prevention approaches with African American male youth.


Tubulointerstitial Nephritis and Uveitis Syndrome: Case Report and Review of the Literature.
To review the literature on tubulointerstitial nephritis and uveitis (TINU) syndrome, and to report a case of a patient with relapsing polychondritis (RP) and TINU syndrome. TINU syndrome is a rare oculorenal inflammatory disorder. It is more common in young women with autoimmune conditions, infections, systemic disease, and previous use of medications. We report the case of a 62-year-old woman with relapsing polychondritis and a 2-year history of acute, recurrent, asymmetric, bilateral, anterior, non-granulomatous uveitis accompanied by tubulointerstitial nephritis. The patient was diagnosed with TINU syndrome associated with relapsing polychondritis. No cases of this association have been reported in the literature. The clinical features of TINU syndrome are discussed based on the published works. TINU is an uncommon syndrome; only about 200 cases have been reported in the literature related to infections, systemic disease, and previous use of medications such as antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). We found that it can be associated with relapsing polychondritis; therefore, it is important to investigate symptoms of this disease since TINU syndrome can co-exist with it.


General practitioners as supervisors in postgraduate clinical education: an integrative review.
General practice supervisors are said to serve as the cornerstones of general practice postgraduate education and therefore it is important to clearly define their roles and what makes them effective. The commonly used definition of a supervisor is not primarily based on general practice and does not cover aspects predicted to be important according to work-based learning theory. We searched for papers published between 1991 and 2011 inclusive, categorised them according to whether they provided empirical evidence, descriptions or recommendations, open-coded the empirical evidence, and used the resulting coding scheme as an analytic framework within which to present a narrative summary of findings. Recommendations and descriptions far outweighed empirical evidence, which showed how supervisors intertwined clinical and educational activities and formed educational alliances with resident doctors that provided a foundation for learning. Residents needed a balance of challenge, usually provided by patients, and support, provided by supervisors. Supervisors established learning environments, assessed residents' learning needs, facilitated learning, monitored the content and process of learning and the well-being of residents, and summarised learning in ways that turned 'know that' into 'know how'. General practice must be expert in ensuring patients are well cared for 'by proxy' and in giving residents just the right amount of support they need to face the challenges posed by those patients. As general practice responds to contemporary clinical demands and rising numbers of undergraduate medical students, it is essential that the ability of general practice supervisors to develop and sustain supportive supervisory relationships with residents is preserved.


Gynaecological cancer and night shift work: A systematic review.
Night shift work can affect hormonal balance, and so might be a risk factor for gynaecological malignancies. This report presents a systematic review on the association between this occupational exposure and the incidence of gynaecological cancers other than breast cancer. We searched for original articles addressing this issue in PubMed/MEDLINE, EMBASE and Web of Science, and used the Newcastle-Ottawa Quality Index to evaluate the methodological quality of those reports selected for review. Globally, we found only six articles, which provided the results of just six research studies: four examined ovarian cancer, two endometrial tumours and two cervical cancer. Our results show that this matter has received scant attention from the research community, and that the little evidence available does not show any clear relationship between night shift work and ovarian, endometrial or cervical cancer. More prospective rigorous studies are needed to evaluate these associations.


Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation.
The mammalian circadian clock consists of multiple transcriptional regulators that coordinate biological processes in a time-of-day-dependent manner. Cardiomyocyte-specific deletion of the circadian clock component, Bmal1 (aryl hydrocarbon receptor nuclear translocator-like protein 1), leads to age-dependent dilated cardiomyopathy and decreased lifespan in mice. We investigated whether cardiomyocyte-specific Bmal1 knockout (CBK) mice display early alterations in cardiac diastolic function, extracellular matrix (ECM) remodeling, and inflammation modulators by investigating CBK mice and littermate controls at 8 and 28 wk of age (i.e., prior to overt systolic dysfunction). Left ventricles of CBK mice exhibited (P < 0.05): 1) progressive abnormal diastolic septal annular wall motion and reduced pulmonary venous flow only at 28 wk of age; 2) progressive worsening of fibrosis in the interstitial and endocardial regions from 8 to 28 wk of age; 3) increased (>1.5 fold) expression of collagen I and III, as well as the matrix metalloproteinases MMP-9, MMP-13, and MMP-14 at 28 wk of age; 4) increased transcript levels of neutrophil chemotaxis and leukocyte migration genes (Ccl2, Ccl8, Cxcl2, Cxcl1, Cxcr2, Il1β) with no change in Il-10 and Il-13 genes expression; and 5) decreased levels of 5-LOX, HO-1 and COX-2, enzymes indicating impaired resolution of inflammation. In conclusion, genetic disruption of the cardiomyocyte circadian clock results in diastolic dysfunction, adverse ECM remodeling, and proinflammatory gene expression profiles in the mouse heart, indicating signs of early cardiac aging in CBK mice.


Low voltage operation of a silver/silver chloride battery with high desalination capacity in seawater.
Technologies for the effective and energy efficient removal of salt from saline media for advanced water remediation are in high demand. Capacitive deionization using carbon electrodes is limited to highly diluted salt water. Our work demonstrates the high desalination performance of the silver/silver chloride conversion reaction by a chloride ion rocking-chair desalination mechanism. Silver nanoparticles are used as positive electrodes while their chlorination into AgCl particles produces the negative electrode in such a combination that enables a very low cell voltage of only Δ200 mV. We used a chloride-ion desalination cell with two flow channels separated by a polymeric cation exchange membrane. The optimized electrode paring between Ag and AgCl achieves a low energy consumption of 2.5 kT per ion when performing treatment with highly saline feed (600 mM NaCl). The cell affords a stable desalination capacity of 115 mg g-1 at a charge efficiency of 98%. This performance aligns with a charge capacity of 110 mA h g-1.


Pneumocystis pneumonia in South African children diagnosed by molecular methods.
Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR. A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded. 202 children [median (interquartile range, IQR) age 3.2 (2.1- 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 - 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality. The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.


Care Values in Dementia: Patterns of Perception and Incongruence Among Family Care Dyads.
Persons with dementia (PWDs) often place greater importance on their care values (i.e., maintaining autonomy and social relations, choosing caregivers, avoiding being a burden) than family caregivers (CGs) perceive, which can detract from dementia care planning (e.g., care arrangements or surrogate decisions). Notable variability has been found across family care dyads (PWD and CG) in their perceptions of care values, suggesting that there may be multiple patterns of perception. The purpose of this study was to characterize distinct patterns of perception of care values in family care dyads. Using cross-sectional data from 228 community-dwelling family care dyads, we quantified dyads' average perceptions and incongruence in perceptions of the importance of everyday care values using multilevel modeling. These scores were then used in a latent class analysis to identify distinct patterns of perception, with the dyad as the unit of analysis. Two distinct patterns of care value perception were identified. 25% of dyads were labeled as "CG underestimating" due to lower average estimations of the importance of PWDs' care values, and a significant amount of dyadic incongruence. Underestimating dyads were characterized by a confirmed diagnosis of dementia, lower cognitive function, and younger age in PWDs, and higher relationship strain in the dyad. Care dyads that fall into an underestimating pattern may be at greater risk for inadequate dementia care planning. Interventions to improve care planning in this higher-risk group may include care values identification with the PWD, strategies for alleviating relationship strain, early-stage planning, and disease education.


Intraventricular Extension of Supratentorial Intracerebral Hemorrhage: The Modified Graeb Scale Improves Outcome Prediction in Lund Stroke Register.
The modified Graeb Scale (mGS) is a semi-quantitative method to assess the extension of intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH). The mGS has been shown to prognosticate outcome after ICH in cohorts derived from convenience samples. We evaluated the external validity of mGS in supratentorial ICH-patients from an unselected cohort. ICH-patients were included prospectively and consecutively in Lund Stroke Register. Follow-up survival status was obtained from the National Census Office; functional outcome was obtained from the Swedish Stroke Register or medical records. Using multivariate analyses, we examined if mGS was related to 30-day survival or poor functional outcome (modified Rankin Scale ≥4) at 90 days. Of 198 supratentorial ICH-patients, 86 (43%) had IVH (median mGS 12, range 1-28). In multivariate regression analyses, the mGS independently predicted 30-day mortality (per point; OR 1.16; 95% CI 1.06-1.27; p = 0.002) and poor functional outcome (OR 1.11; 95% CI 1.02-1.20; p = 0.011) after ICH. In receiver-operator characteristic analysis, the addition of mGS tended to be associated with a higher prognostic accuracy for survival (area under curve 0.886 vs. not including mGS 0.812; p = 0.053). The mGS improves outcome prediction after supratentorial ICH beyond other previously established factors in an unselected population.


Effects of long-term 50 Hz magnetic field exposure on the micro nucleated polychromatic erythrocyte and blood lymphocyte frequency and argyrophilic nucleolar organizer regions in lymphocytes of mice.
We aimed to investigate the effects of weak extremely low frequency electromagnetic fields (ELF-EMFs) on the nucleus size, the silver staining nucleolar organizer regions (AgNORs), the frequency of micro nucleated peripheral blood lymphocytes (MPBLs) and the micro nucleated polychromatic erythrocytes (MPCEs). One hundred and twenty Swiss albino mice were equally divided into 6 groups. The study groups were exposed to 1, 2, 3, 4 and 5 microT 50 Hz-EMFs for 40 days. Micronucleus number (MN) per PBL was determined.. ELF-EMF exposure caused a nonlinear decline of nucleus area. A sharp drop occurred in AgNOR area of 1 microT group, and following it gained an insignificantly higher level than that of the control group. The field did not change mean AgNOR numbers per nucleus of the groups. Relative AgNOR area had the highest level in 1 microT-exposure group, and the level was quite similar to that of the 5 microT-exposure group. The remaining groups had significantly lower values quite similar to that of the control level. The field exposure at any intensity did not affect significantly the frequency of either MPBLs or MPCEs. The number of MN per PBL in the 4 and 5 microT-exposure groups were significantly higher than those of the lower intensity exposure groups. The males in 4 microT-exposure group displayed the highest MN number per PBL, whereas values changed in a nonlinear manner. The results of the present study suggest that </=5 microT intensities of 50 Hz EMFs did not cause genotoxic effect on the mouse.


Diverse Temporal Dynamics of Repetition Suppression Revealed by Intracranial Recordings in the Human Ventral Temporal Cortex.
Repeated stimulus presentations commonly produce decreased neural responses-a phenomenon known as repetition suppression (RS) or adaptation-in ventral temporal cortex (VTC) of humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from nine human subjects implanted with intracranial electrodes in the VTC. The subjects viewed nonrepeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: 1) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower-frequency bands; 2) RS of the HFB signal is associated with lower peak magnitude (PM), lower total responses, and earlier peak responses; and 3) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.


The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy.
PD-L1 is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors, as well as their roles in determining therapeutic efficacies are unknown. Here we identified, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent IFN-γ signature and potentially signified pro-inflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1+ cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1+ cancer cells susceptive to apoptosis. Importantly, PD-L1+ cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune checkpoint blockade. Therapeutic strategy combining immune checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited caner regression. Our results provide insight into the functional features of PD-L1+ tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune checkpoint blockade therapy.


Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.
Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.


Monoclonal antibodies against Escherichia coli heat-stable toxin (STa) and their use in a diagnostic ST ganglioside GM1-enzyme-linked immunosorbent assay.
Seven monoclonal antibodies (MAbs) against heat-stable enterotoxin (ST) from a human Escherichia coli isolate were prepared and evaluated for their usefulness in an ST immunodetection assay, the ST ganglioside GM1-enzyme-linked immunosorbent assay (ELISA). This assay is based on the ability of STa, as present in, for example, culture filtrates from ST-producing E. coli, to inhibit specific anti-ST antibody from binding to solid-phase-bound ST ganglioside (GM1-bound ST-cholera B subunit). Four of the MAbs were of immunoglobulin G1 (IgG1), one was of IgG2b, and two were of IgM isotype. All the IgG1 MAbs could be completely inhibited by addition of free ST; 0.2 to 0.4 ng of purified ST inhibited binding of these MAbs by 50%. The non-IgG1 MAbs were, in contrast, not inhibited by 200-fold-higher amounts of purified ST, probably because they were directed against linkage epitopes or were of low affinity or both. When the IgG1 MAbs were tested in the ST GM1-ELISA, ST could be detected in culture filtrates from stock human E. coli isolates with 100% sensitivity and specificity. ST in filtrates from fresh stool cultures was demonstrated with higher sensitivity with the MAbs ST GM1-ELISA than with the conventional infant mouse test. Both subtypes of STa, STaI and STaII, could be detected by the ST GM1-ELISA by using either IgG1 MAb in the immunodetection step, whereas infant-mouse-active ST from Yersinia enterocolitica failed to react.


Antiangiogenic activity of a neutralizing human single-chain antibody fragment against fibroblast growth factor receptor 1.
Fibroblast growth factor receptor-1 (FGFR-1) transduces proangiogenic and proliferative signals in human cancers. Thus, FGFR-1 may represent a target for the development of antiangiogenic/antineoplastic therapies. We screened a human single-chain fragment variable (scFv) antibody phage display library against the extracellular domain of the FGFR-1-IIIc isoform that harbors the FGF binding site. Several phages were isolated and tested for specificity and sensitivity, and the most promising antibody fragment RR-C2 was characterized for its biochemical and biological properties. ScFv RR-C2 specifically recognizes FGFR-1α and FGFR-1β isoforms in ELISA, Western blotting, and surface plasmon resonance analysis with a K(d) value of 300 and 144 nmol/L for the 2 receptor isoforms, respectively. The antibody fragment also recognizes FGFR-1 when the receptor is exposed on the cell surface, thus preventing the formation of the ternary complex among FGFR-1, its ligand FGF2, and cell surface heparan sulfate proteoglycans. Accordingly, scFv RR-C2 specifically inhibits FGF2-mediated mitogenic activity in endothelial cells of human, bovine, and murine origin in a nanomolar range of concentrations. Also, the antibody fragment prevents FGF2-triggered sprouting of both human umbilical vein endothelial cell spheroids and of murine endothelium from aortic rings. Finally, the antibody fragment hampers the angiogenic activity exerted both by FGF2 in the chick embryo chorioallantoic membrane assay and by S115 mouse mammary tumor cells in the Matrigel plug assay. Taken together, the data show that scFv RR-C2 recognizes and neutralizes FGFR-1 activity in different animal species, including humans, thus representing a novel tool for the development of antiangiogenic/antineoplastic therapies.


Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States.
Use of ketamine in the prehospital setting may be advantageous due to its potent analgesic and sedative properties and favorable risk profile. Use in the military setting has demonstrated both efficacy and safety for pain relief. The purpose of this study was to assess ketamine training, use, and perceptions in the civilian setting among nationally certified paramedics (NRPs) in the United States. A cross-sectional survey of NRPs was performed. The electronic questionnaire assessed paramedic training, authorization, use, and perceptions of ketamine. Included in the analysis were completed surveys of paramedics who held one or more state paramedic credentials, indicated "patient care provider" as their primary role, and worked in non-military settings. Descriptive statistics were calculated. A total of 14,739 responses were obtained (response rate=23%), of which 10,737 (73%) met inclusion criteria and constituted the study cohort. Over one-half (53%) of paramedics reported learning about ketamine during their initial paramedic training. Meanwhile, 42% reported seeking ketamine-related education on their own. Of all respondents, only 33% (3,421/10,737) were authorized by protocol to use ketamine. Most commonly authorized uses included pain management (55%), rapid sequence intubation (RSI; 72%), and chemical restraint/sedation (72%). One-third of authorized providers (1,107/3,350) had never administered ketamine, with another 32% (1,070/3,350) having administered ketamine less than five times in their career. Ketamine was perceived to be safe and effective as the vast majority reported that they were comfortable with the use of ketamine (94%) and would, in similar situations (95%), use it again. This was the first large, national survey to assess ketamine training, use, and perceptions among paramedics in the civilian prehospital setting. While training related to ketamine use was commonly reported among paramedics, few were authorized to administer the drug by their agency's protocols. Of those authorized to use ketamine, most paramedics had limited experience administering the drug. Future research is needed to determine why the prevalence of ketamine use is low and to assess the safety and efficacy of ketamine use in the prehospital setting. Buckland DM , Crowe RP , Cash RE , Gondek S , Maluso P , Sirajuddin S , Smith ER , Dangerfield P , Shapiro G , Wanka C , Panchal AR , Sarani B . Ketamine in the prehospital environment: a national survey of paramedics in the United States. Prehosp Disaster Med. 2018;33(1):23-28.


Irreversible hydrocolloid: an unusual presentation of esophageal obstruction.
Upper digestive tract obstruction can occur after ingestion of various types of foreign bodies. However to the best of our knowledge, no case of a near-total obstruction caused by an irreversible hydrocolloid has heretofore been reported in the literature. We present just such a case, and we discuss our preferred method of removing foreign bodies from the cervical esophagus.


Deep mRNA sequencing for in vivo functional analysis of cardiac transcriptional regulators: application to Galphaq.
Transcriptional profiling can detect subclinical heart disease and provide insight into disease etiology and functional status. Current microarray-based methods are expensive and subject to artifact. To develop RNA sequencing methodologies using next generation massively parallel platforms for high throughput comprehensive analysis of individual mouse cardiac transcriptomes. To compare the results of sequencing- and array-based transcriptional profiling in the well-characterized Galphaq transgenic mouse hypertrophy/cardiomyopathy model. The techniques for preparation of individually bar-coded mouse heart RNA libraries for Illumina Genome Analyzer II resequencing are described. RNA sequencing showed that 234 high-abundance transcripts (>60 copies/cell) comprised 55% of total cardiac mRNA. Parallel transcriptional profiling of Galphaq transgenic and nontransgenic hearts by Illumina RNA sequencing and Affymetrix Mouse Gene 1.0 ST arrays revealed superior dynamic range for mRNA expression and enhanced specificity for reporting low-abundance transcripts by RNA sequencing. Differential mRNA expression in Galphaq and nontransgenic hearts correlated well between microarrays and RNA sequencing for highly abundant transcripts. RNA sequencing was superior to arrays for accurately quantifying lower-abundance genes, which represented the majority of the regulated genes in the Galphaq transgenic model. RNA sequencing is rapid, accurate, and sensitive for identifying both abundant and rare cardiac transcripts, and has significant advantages in time- and cost-efficiencies over microarray analysis.


Does child gender determine household decision for health care in rural Thatta, Pakistan?
In South Asia, gender disparity in child mortality is highest in Pakistan. We examined the influence of child gender on household decision regarding health care. Prevalence ratios were calculated for 3740 children aged 1-59 months from 92 randomly selected villages of rural Pakistan using a cluster-adjusted log-binomial model. Level 1 variables included child and household characteristics and level 2 included village characteristics. There were 25 more girl deaths than boys per 1000 live births (95% CI: 13.9, 48.6) among post-neonates and 38 more among children aged 12-59 months (95% CI: 10.5, 65.5). However, in adjusted analysis, gender was not a significant predictor of illness reporting, visit to health facilities, choice of provider, hospitalization and health expenditure. Significant predictors of health care were child's age, illness characteristics, number of children in the family, household socio-economic status and absence of girls' school in the village. Differential care seeking for boys and girls is not seen in Thatta despite clear differences in mortality ratios. This calls for more creative research to identify pathways for gender differential in child mortality. Factors identified as influencing child health care and amenable to modification include poverty alleviation and girls' education.


Restrictive educational placements increase adolescent risks for students with early-starting conduct problems.
Students with early-starting conduct problems often do poorly in school; they are disproportionately placed in restrictive educational placements outside of mainstream classrooms. Although intended to benefit students, research suggests that restrictive placements may exacerbate the maladjustment of youth with conduct problems. Mixed findings, small samples, and flawed designs limit the utility of existing research. This study examined the impact of restrictive educational placements on three adolescent outcomes (high school noncompletion, conduct disorder, depressive symptoms) in a sample of 861 students with early-starting conduct problems followed longitudinally from kindergarten (age 5-6). Causal modeling with propensity scores was used to adjust for confounding factors associated with restrictive placements. Analyses explored the timing of placement (elementary vs. secondary school) and moderation of impact by initial problem severity. Restrictive educational placement in secondary school (but not in elementary school) was iatrogenic, increasing the risk of high school noncompletion and the severity of adolescent conduct disorder. Negative effects were amplified for students with conduct problem behavior with less cognitive impairment. To avoid harm to students and to society, schools must find alternatives to restrictive placements for students with conduct problems in secondary school, particularly when these students do not have cognitive impairments that might warrant specialized educational supports.


Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells.
Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1alpha expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.


Tracking Resilience to Infections by Mapping Disease Space.
Infected hosts differ in their responses to pathogens; some hosts are resilient and recover their original health, whereas others follow a divergent path and die. To quantitate these differences, we propose mapping the routes infected individuals take through "disease space." We find that when plotting physiological parameters against each other, many pairs have hysteretic relationships that identify the current location of the host and predict the future route of the infection. These maps can readily be constructed from experimental longitudinal data, and we provide two methods to generate the maps from the cross-sectional data that is commonly gathered in field trials. We hypothesize that resilient hosts tend to take small loops through disease space, whereas nonresilient individuals take large loops. We support this hypothesis with experimental data in mice infected with Plasmodium chabaudi, finding that dying mice trace a large arc in red blood cells (RBCs) by reticulocyte space as compared to surviving mice. We find that human malaria patients who are heterozygous for sickle cell hemoglobin occupy a small area of RBCs by reticulocyte space, suggesting this approach can be used to distinguish resilience in human populations. This technique should be broadly useful in describing the in-host dynamics of infections in both model hosts and patients at both population and individual levels.


[Development of opioid tolerance -- molecular mechanisms and clinical consequences].
One often identified effect of opioid administration is that of the development of tolerance to the analgesic effect. While it is generally agreed that tolerance to opioid analgesia does occur, it does not appear to be a limiting factor. Dose escalation in chronic pain therapy is considered to be predominantly a consequence of increasing pain, which is a result of increasing nociceptive input as the disease progresses. The underlying cause of tolerance to opioids, however, as commonly identified in the ICU can be identified as an adaptation process. When the opioid is given continuously several causes of adaptation can be identified, all of which can be traced back to the cellular and molecular level. Initial effects of opioid administration in most individuals are analgesia, sedation, nausea/vomiting, respiratory depression, pupillary constriction, constipation and euphoria or dysphoria. However, numerous studies and clinical experience suggest that tolerance to different opioid effects develop at different rates, which has been termed selective tolerance. While tolerance to nausea, vomiting, sedation, euphoria and respiratory depression occur rapidly, there is minimal development of tolerance to constipation and miosis. Such diversity suggest receptor-related differences in the speed of development of tolerance. In the ICU other compounds such as benzodiazepines, when given together with opioids, seem to speed up the rate of development of tolerance of the latter. Such an effect very likely is due to a reduction in activity of the descending inhibitory nervous system. In addition, there is surmountable data suggesting that the higher the intrinsic activity of the opioid at only one receptor site, lesser receptors are needed in order to induce a potent analgesic effect. As a net result the incidence of tolerance is less likely to become clinically apparent when potent ligands such as fentanyl or sufentanil are administered. N-METHYL-D-ASPARTATE (NMDA) ACTIVATION, OPIOID RECEPTOR INTERNALIZATION AND DESENSITIZATION: An altered metabolism has little effect on the rate of development of tolerance. In chronic pain treatment with morphine, however, an increased ratio of the metabolite morphine-3-glucuronide, with antiopioid effects, to morphine-6-glucuronide is associated with staggering doses of the analgesic. Opioids which interact with micro - and/or kappa-binding sites, demonstrate an adaptation process called desensitization which is due to a reduced interaction with the internal second messenger system called G-protein. This is only a short-lived phenomenon following binding of the ligand. Another underlying mechanism of tolerance development is that of internalization of the opioid receptors. This short-lived phenomenon, termed endocytosis, results in lesser binding sites available for the mediation of analgesia. Another and more relevant mechanism of long-term opioid binding is that of subsequent protein kinase C (PKC), phospholipase C (PLC) translocation and activation of nitric oxide synthetase (NOS). All of this contributes to a N-methyl-D-aspartate (NMDA) receptor activation with ensuing antiopioid effect and tolerance. Most likely genetic difference in opioid receptor synthesis and difference in their affinities for various ligands is the cause for the wide margin of dose variability in patients (genetic polymorphism). Once tolerance to the analgesic effect of the opioid is observed and in order to avoid unnecessary further development of tolerance, simultaneous administration of other receptor mediated analgesics is advocated. In the perioperative period strategies like the multimodal analgesic concept is fostered. It consists of the simultaneous administration of low-dose ketamine, co-administration of an alpha 2-agonist, and the administration of a selective COX-2 inhibitor (refecoxib, parecoxib) respectively. In chronic pain therapy combined administration with either dextromethorpharphane, or opioid rotation of a more potent ligand such as methadone, fentanyl TTS or oxycodone is suggested. Since conversion factors are not reliable in opioid rotation, it is best to start off with 50 % of the equivalent dose and rapidly titrate to the desired effect. With regard to tolerance development in the ICU, co-administration of an alpha 2-agonist (clonidine, dexmedetomidine), and daily intermittent cessation of benzodiazepine administration are advocated. Since continuous dosing of an opioid, commonly handled in the ICU setting is more likely to induce tolerance, intermittent administration is advocated. Taken together, there is an abundance of experimental data which suggests, that with every dose of an opioid several adaptive processes are being initiated. Due to genetic polymorphism such adaptation is seen clinically with striking individual different dosages, the degree and the time of onset of tolerance. Although tolerance development may result in staggering doses of an opioid, there is no reason to evade the use of such agents. On the contrary, the concept of multimodal analgesia consisting of the simultaneous use of analgesics with a different mode of action can counteract tolerance development.


Binocular summation of contrast remains intact in strabismic amblyopia.
Strabismic amblyopia is typically associated with several visual deficits, including loss of contrast sensitivity in the amblyopic eye and abnormal binocular vision. Binocular summation ratios (BSRs) are usually assessed by comparing contrast sensitivity for binocular stimuli (sens(BIN)) with that measured in the good eye alone (sens(GOOD)), giving BSR = sens(BIN)/sens(GOOD). This calculation provides an operational index of clinical binocular function, but does not assess whether neuronal mechanisms for binocular summation of contrast remain intact. This study was conducted to investigate this question. Horizontal sine-wave gratings were used as stimuli (3 or 9 cyc/deg; 200 ms), and the conventional method of assessment (above) was compared with one in which the contrast in the amblyopic eye was adjusted (normalized) to equate monocular sensitivities. In nine strabismic amblyopes (mean age, 32 years), the results confirmed that the BSR was close to unity when the conventional method was used (little or no binocular advantage), but increased to approximately radical2 or higher when the normalization method was used. The results were similar to those for normal control subjects (n = 3; mean age, 38 years) and were consistent with the physiological summation of contrast between the eyes. When the normal observers performed the experiments with a neutral-density (ND) filter in front of one eye, their performance was similar to that of the amblyopes in both methods of assessment. The results indicate that strabismic amblyopes have mechanisms for binocular summation of contrast and that the amblyopic deficits of binocularity can be simulated with an ND filter. The implications of these results for best clinical practice are discussed.


Expression and regulation of cornified envelope proteins in human corneal epithelium.
Stratified squamous epithelial cells assemble a specialized protective barrier structure on their periphery, termed the cornified envelope. The purpose of this study was to evaluate the presence and distribution of cornified envelope precursors in human corneal epithelium, their expression in human corneal epithelial cell cultures, and the effect of ultraviolet radiation (UVB) and transglutaminase (TG) inhibition on their expression. Tissue distribution of small proline-rich proteins (SPRRs) and filaggrin and involucrin was studied in human cornea sections by immunofluorescence staining. Primary human corneal epithelial cells (HCECs) from limbal explants were used in cell culture experiments. A single dose of UVB at 20 mJ/cm2 was used to stimulate these cells, in the presence or absence of mono-dansyl cadaverine (MDC), a TG inhibitor. SPRR2 and involucrin protein levels were studied by immunofluorescence staining and Western blot analysis. Gene expression of 12 proteins was investigated by semiquantitative reverse transcription-polymerase chain reaction. In human cornea tissue, SPRR1, SPRR2, filaggrin, and involucrin protein expression were detected in the central and peripheral corneal and limbal epithelium. In HCECs, SPRR2 and involucrin proteins were detected in the cytosolic fraction, and involucrin levels increased after UVB. Both SPRR2 and involucrin levels accumulated in the presence of MDC. Nine genes including involucrin, SPRR (types 1A, 1B, 2A, 2B, and 3), late envelope protein (LEP) 1 and 16, and filaggrin were expressed by HCECs. SPRR 4, loricrin, and LEP 6 transcripts were not detected. UVB downregulated SPRR (2A, 2B) and LEP 1 transcripts. Various envelope precursors are expressed in human corneal epithelium and in HCECs, acute UVB stress differentially alters their expression in HCECs. The expression of envelope precursors and their rapid modulation by UVB supports the role of these proteins in the regulation of ocular surface stress. TG function may be relevant in the regulation of soluble precursors in UVB-stimulated corneal epithelium.


Intentions to maintain adherence to mammography.
Recent attention has focused on moving women from having initial mammograms to maintaining adherence to regular mammography schedules. We examined behavioral intentions to maintain mammography adherence, which include the likelihood of performing a behavior, and implementation intentions, specific action plans to obtain mammograms. Potential predictors were Theory of Planned Behavior constructs, previous barriers, previous mammography maintenance, and age. Respondents were 2062 currently adherent women due for their next mammograms in 3-4 months according to American Cancer Society recommendations for annual screening. Statistical models were used to examine predictors of behavioral and two implementation intentions, including having thought about where women would get their next mammograms and having thought about making appointments. With the exception of pros, cons, and subjective norms, all variables predicted behavioral intentions (p <or= 0.05). Stronger perceived control, previous mammography maintenance, and one barrier (vs. none) predicted being more likely to have thought about where to get their next mammograms. Previous maintenance and no barriers (vs. two) predicted being more likely to have thought about making appointments. Our findings suggest that among women currently adherent to mammography, volitional factors, such as barriers, may be better predictors of implementation intentions than motivational factors, such as attitudes. Implementation variables may be useful in understanding how women move from intentions to action. Future research should examine how such factors relate to mammography maintenance behaviors and can be integrated into behavior change interventions.


Learning Complexity-Aware Cascades for Pedestrian Detection.
The problem of pedestrian detection is considered. The design of complexity-aware cascaded pedestrian detectors, combining features of very different complexities, is investigated. A new cascade design procedure is introduced, by formulating cascade learning as the Lagrangian optimization of a risk that accounts for both accuracy and complexity. A boosting algorithm, denoted as complexity aware cascade training (CompACT), is then derived to solve this optimization. CompACT cascades are shown to seek an optimal trade-off between accuracy and complexity by pushing features of higher complexity to the later cascade stages, where only a few difficult candidate patches remain to be classified. This enables the use of features of vastly different complexities in a single detector. In result, the feature pool can be expanded to features previously impractical for cascade design, such as the responses of a deep convolutional neural network (CNN). This is demonstrated through the design of pedestrian detectors with a pool of features whose complexities span orders of magnitude. The resulting cascade generalizes the combination of a CNN with an object proposal mechanism: rather than a pre-processing stage, CompACT cascades seamlessly integrate CNNs in their stages. This enables accurate detection at fairly fast speeds.


Telepsychiatry- Based Care for the Treatment Follow-Up of Iranian War Veterans with Post-Traumatic Stress Disorder: A Randomized Controlled Trial.
Physical limitations, distance, and time are major obstacles to access to mental health services for veterans and soldiers. This study was aimed at comparing the efficacy of telepsychiatry and face-to-face consultation as methods of treating post-traumatic stress disorder (PTSD). The comparison was based on treatment costs, access to health services, completion of therapy sessions, and patient satisfaction as variables. This research was a double blinded clinical trial supported by Tabriz University of Medical Sciences and conducted in 2015 to 2016 in Tabriz, Iran. Totally, 60 patients were included in the study. Through simple randomization, the patients were divided into experimental and control groups, both of whom were treated through face-to-face consultations for the first 3 sessions. Six follow-up sessions were then held remotely with the experimental group and face to face with the control group. Data were collected using a self-designed and reliable questionnaire and entered in SPSS, version 16. Intergroup comparisons were performed using descriptive statistical measures. Finally, the results were tested using the t test method. A significant relationship was found between the use of information technology and increased patient satisfaction, completion of therapy sessions, and reduction in treatment costs; however, no significant difference was found between the groups in terms of reduction in waiting time and access to a psychiatrist. Telepsychiatry is an effective means of delivering mental health services to psychiatric outpatients living in remote areas with limited resources. The results provide preliminary support for the use of telepsychiatry in treating PTSD and improving access to care. Trial Registration Number: IRCT2016020826449N1.


Modulation transfer function measurement of sparse-array sensors using a self-calibrating fringe pattern.
A simple method for the measurement of the pixel modulation transfer function (MTF) of sparse-array (extended MTF) sensors has been developed. We use a phase-shifting Twyman-Green interferometer to generate a series of single spatial-frequency fringe patterns incident on the sensor The resulting signal modulation is measured. We achieve self-calibration by restricting the measured spatial frequencies to multiples of the Nyquist frequency. The aliased patterns at these frequencies are unique and easily identifiable. Spatial frequencies of 480 cycles/mm are generated and measured. This frequency value is more than ten times that of the sensor sampling frequency. The expected MTF shape is obtained at multiples of the sampling frequency. At odd multiples of the Nyquist frequency, the MTF's are affected by the electronic bandwidth and cross talk in the charge-injection device sensor.


Epidemiology of osteoporosis.
Osteoporotic fractures represent a significant public health burden, which is set to increase in future generations. Lifetime risk is high and lies within the range of 40% to 50% in women and 13% to 22% in men. Life expectancy is increasing worldwide, and it is estimated that the number of individuals aged 65 years and older will increase from the current figure of 323 million to 1555 million by the year 2050. These demographic changes alone can be expected to cause the number of hip fractures occurring worldwide to increase from 1.66 million in 1990 to 6.26 million in 2050. Based on current trends, hip fracture rates might increase in the United Kingdom from 46,000 in 1985 to 117,000 in 2016. The societal cost of these fractures is high; cost-effectiveness analyses showed cost-effectiveness in treating high-risk patients with antiresorptive drugs, particularly if administered as soon as possible after a first fragility fracture.


The scaling of population persistence with carrying capacity does not asymptote in populations of a fish experiencing extreme climate variability.
Despite growing concerns regarding increasing frequency of extreme climate events and declining population sizes, the influence of environmental stochasticity on the relationship between population carrying capacity and time-to-extinction has received little empirical attention. While time-to-extinction increases exponentially with carrying capacity in constant environments, theoretical models suggest increasing environmental stochasticity causes asymptotic scaling, thus making minimum viable carrying capacity vastly uncertain in variable environments. Using empirical estimates of environmental stochasticity in fish metapopulations, we showed that increasing environmental stochasticity resulting from extreme droughts was insufficient to create asymptotic scaling of time-to-extinction with carrying capacity in local populations as predicted by theory. Local time-to-extinction increased with carrying capacity due to declining sensitivity to demographic stochasticity, and the slope of this relationship declined significantly as environmental stochasticity increased. However, recent 1 in 25 yr extreme droughts were insufficient to extirpate populations with large carrying capacity. Consequently, large populations may be more resilient to environmental stochasticity than previously thought. The lack of carrying capacity-related asymptotes in persistence under extreme climate variability reveals how small populations affected by habitat loss or overharvesting, may be disproportionately threatened by increases in extreme climate events with global warming.


Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps).
A toxicovenomic study was performed on the venom of the green mamba, Dendroaspis angusticeps. Forty-two different proteins were identified in the venom of D. angusticeps, in addition to the nucleoside adenosine. The most abundant proteins belong to the three-finger toxin (3FTx) (69.2%) and the Kunitz-type proteinase inhibitor (16.3%) families. Several sub-subfamilies of the 3FTxs were identified, such as Orphan Group XI (Toxin F-VIII), acetylcholinesterase inhibitors (fasciculins), and aminergic toxins (muscarinic toxins, synergistic-like toxins, and adrenergic toxins). Remarkably, no α-neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA and immunoprecipitated the crude venom by gel immunodiffusion. The synergistic mechanism of toxicity constitutes a challenge for the development of effective recombinant antibodies, as it requires the identification of the most relevant synergistic toxins. Envenomings by elapid snakes of the genus Dendroaspis, collectively known as mambas, represent a serious medical problem in sub-Saharan Africa. The development of novel antivenoms and of recombinant neutralizing antibodies demands the identification of the most relevant toxins in these venoms. In this study, a bottom-up approach was followed for the study of the proteome of the venom of the Eastern green mamba, D. angusticeps. Forty-two different proteins were identified, among which the three-finger toxin (3FTx) family, characteristic of elapid venoms, was the most abundant, followed by the Kunitz-type proteinase inhibitor family. In addition, several other protein families were present in the venom, together with the nucleoside adenosine. No α-neurotoxins were identified within the family of 3FTxs in the venom of D. angusticeps, in contrast to the venom of Dendroaspis polylepis, in which α-neurotoxins are largely responsible for the toxicity. With one exception, HPLC fractions from D. angusticeps venom did not kill mice at the doses tested. This underscores that the toxicity of the whole venom is due to the synergistic action of various components, such as fasciculins and dendrotoxins, and probably other synergistically-acting toxins. Thus, the venoms of these closely related species (D. angusticeps and D. polylepis) seem to have different mechanisms to subdue their prey, which may be related to different prey preferences, as D. angusticeps is predominantly arboreal, whereas D. polylepis lives mostly in open bush country and feeds mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality in mice and showed a pattern of broad immunorecognition of the various venom fractions. It is necessary to identify the toxins responsible for the synergistic mode of toxicity in this venom, since they are the targets for the development of recombinant antibodies for the treatment of envenomings.


Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women.
We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.


Assessment of Diet Quality in Chilean Urban Population through the Alternate Healthy Eating Index 2010: A Cross-Sectional Study.
Most worldwide causes of disease and death are strongly associated with dietary factors and the application of eating indexes has proved to be a useful tool to determine diet quality in populations. The aim of this study was to evaluate the diet quality in Chile through the application of the Alternate Healthy Eating Index 2010 (AHEI-2010). A representative sample (n = 879) of Chilean urban population aged 15⁻65 years old from the Latin American Study of Nutrition and Health (Estudio Latinoamericano de Nutrición y Salud; ELANS) was used. Dietary intake data were obtained through two 24-hour food recalls and one beverage frequency questionnaire, which were used to calculate AHEI-2010 and its association with sociodemographic and anthropometric variables. In this Chilean sample, the AHEI-2010 score was 43.7 ± 7.8 points (mean ± SD). Trans fats and sodium intake were the highest scoring AHEI-2010 components whereas sugar-sweetened beverages and whole grains had the lowest score. Women, older subjects, and individuals in medium-high socioeconomic levels had significantly higher mean AHEI-2010 scores. No association was found between AHEI-2010 and body mass index (BMI), or nutritional status. Conclusions: Diet quality in the Chilean urban population aged 15⁻65 years old is far from optimal. Thus, there is room for significant improvement of diet quality in Chile through design and implementation of public health policies, particularly in high-risk groups for chronic diseases.


Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome.
The human T-cell leukemia (lymphotropic) virus type III (HTLV-III) appears to be central to the causation of the acquired immune deficiency syndrome (AIDS). Two full-length integrated proviral DNA forms of HTLV-III have now been cloned and analyzed, and DNA sequences of the virus in cell lines and fresh tissues from patients with AIDS or AIDS-related complex (ARC) have been characterized. The results revealed that (i) HTLV-III is an exogenous human retrovirus, approximately 10 kilobases in length, that lacks nucleic acid sequences derived from normal human DNA; (ii) HTLV-III, unlike HTLV types I and II, shows substantial diversity in its genomic restriction enzyme cleavage pattern; (iii) HTLV-III persists in substantial amounts in cells as unintegrated linear DNA, an uncommon property that has been linked to the cytopathic effects of certain animal retroviruses; and (iv) HTLV-III viral DNA can be detected in low levels in fresh (primary) lymphoid tissue of a minority of patients with AIDS or ARC but appears not to be present in Kaposi's sarcoma tissue. These findings have important implications concerning the biological properties of HTLV-III and the pathophysiology of AIDS and Kaposi's sarcoma.


Polyvinyl pyrrolidone: a novel cryoprotectant in islet cell cryopreservation.
The present study was performed on the basis of the hypothesis that the low molecular weight (MW) compounds, DMSO and glycerol, permeate the cell and interact hydrophobically with intracellular proteins, thereby perturbing the cytoskeletal architecture of frozen cells and diminishing islet cell integrity and function. Isolated rat islets were cultured overnight (18-24 h) at 37 degrees C in RPMI medium supplemented with 10% fetal calf serum and 1% mixture of penicillin/streptomycin. Using a programmable temperature controller, samples of precounted islets were then frozen under liquid nitrogen, in the presence of either 2 M DMSO (MW = 0.078 kDa), 3 M glycerol (MW = 0.092 kDa), 5% polyethylene glycol (PEG, MW = 20 kDa), or 10% polyvinylpyrrolidone (PVP, MW = 40 kDa), and stored at -80 degrees C for 1 week. Following thawing and overnight (18-24 h) culture, intact islet recovery was determined by islet counting after dithizone staining. Islet function was assessed by determination of glucose-stimulated insulin secretion in perifusion experiments with Krebs-Ringer bicarbonate buffer, pH 7.4, containing either basal (3.3 mM) or high (16.7 mM) glucose concentrations. The assessment of islet recovery and function of all cryopreserved samples was performed only after thawing and overnight culture (18-24 h) of islets. The mean +/- SEM percent intact islet recovery was higher with PVP compared with DMSO (82 +/- 4.6 vs. 62.7 +/- 3.1%, respectively, p < 0.005, n = 9). Furthermore, the glucose stimulation index of insulin secretion by islets taken from samples frozen with PEG and PVP, after thawing and overnight culture, was comparable to that of freshly isolated islets, in contrast to DMSO and glycerol. There was no significant difference in intact islet recovery and function between samples frozen with PVP and those frozen with PEG. Samples frozen with DMSO and glycerol had similar results in islet recovery and function. These data show that PVP is a new and potent cryoprotectant for islet cell freezing.


HIV seroprevalence and its effect on outcome of moderate to severe burn injuries: A Ugandan experience.
HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. This study was conducted to establish the prevalence of HIV among burn patients in our setting and to compare the outcome of these patients who are HIV positive with those who are HIV negative. This was a prospective cohort study involving burn injury patients admitted to Mulago Hospital between November 2005 and February 2006. Patients were stratified into HIV positive (exposed) group and HIV-negative (unexposed) group. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 11.5. Of the 130 patients included in the study, 17 (13.1%) patients tested HIV positive and this formed the study (exposed) group. The remaining 113 patients (86.9%) formed the control (unexposed) group. In the HIV positive group, females outnumbered males by a ratio of 1.4:1 and the mean age was 28.4 ± 21.5 years (range 3 months-34 years). 64.7% of HIV positive patients reported to have risk factors for HIV infection. Of these, multiple sexual partners [Odds Ratio 8.44, 95% C.I. (3.87-143.23), P = 0.011] and alcoholism [Odds Ratio 8.34, 95% C.I. (5.76-17.82), P = 0.002] were found to be independently and significantly associated with increased risk to HIV infection. The mean CD4 count for HIV positive and HIV negative patients were 394 ± 328 cells/μL and 912 ± 234 cells/μL respectively which is statistically significant (P = 0.001). There was no difference in the bacteria cultured from the wounds of HIV positive and negative patients (P = 0.322). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.001). ). Skin grafting was carried out in 35.3% of HIV negative patients and 29.4% of HIV positive patients with no significant difference in skin graft take and the degree of healed burn on discharge was the same (P = 0.324). There was no significant difference in hospital stay between HIV positive and negative patients (P = 0.674). The overall mortality rate was 11.5%. Using multivariate logistic regression analysis, mortality rate was found to be independently and significantly related to the age of the patient, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (p-value < 0.001). HIV infection is prevalent among burn injury patients in our setting and thus presents an occupational hazard to health care workers who care for these patients. All burn health care workers in this region need to practice universal precautions in order to reduce the risk of exposure to HIV infection and post-exposure prophylaxis should be emphasized. The outcome of burn injury in HIV infected patients is dependent upon multiple variables such as age of the patient, inhalation injury and %TBSA and not the HIV status alone.


New, improved, and practical k-stem sequence similarity measures for probe design.
We define new measures of sequence similarity for oligonucleotide probe design. These new measures incorporate the nearest neighbor k-stem motifs in their definition, but can be efficiently computed by means of a bit-vector method. They are not as computationally costly as algorithms that predict nearest neighbor hybridization potential. Our new measures for sequence similarity correlate significantly better with nearest neighbor thermodynamic predictions than either BLAST or the standard edit or insertion-deletion defined similarities already in use in many different probe design applications.


MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1.
The IFN-α-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Genetic evidence suggested that capsid is the viral determinant for restriction by MxB. This work explores the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in restriction. We showed that MxB binds to the HIV-1 core and that this interaction leads to inhibition of the uncoating process of HIV-1. These results identify MxB as an endogenously expressed protein with the ability to inhibit HIV-1 uncoating. In addition, we found that a benzimidazole-based compound known to have a binding pocket on the surface of the HIV-1 capsid prevents the binding of MxB to capsid. The use of this small-molecule identified the MxB binding region on the surface of the HIV-1 core. Domain mapping experiments revealed the following requirements for restriction: 1) MxB binding to the HIV-1 capsid, which requires the 20 N-terminal amino acids, and 2) oligomerization of MxB, which is mediated by the C-terminal domain provides the avidity for the interaction of MxB with the HIV-1 core. Overall our work establishes that MxB binds to the HIV-1 core and inhibits the uncoating process of HIV-1. Moreover, we demonstrated that HIV-1 restriction by MxB requires capsid binding and oligomerization.


Effect of drying on leaching testing of treated municipal solid waste incineration APC-residues.
Air-pollution-control (APC) residues from waste incinerators are hazardous waste according to European legislation and must be treated prior to landfilling. Batch and column leaching data determine which type of landfill can receive the treated APC-residues. CEN standards are prescribed for the batch and column leaching test; however, these standards do not specify whether or not the residue samples should be dried prior to the leaching testing. Laboratory tests were performed in parallel (dried/non-dried) on treated APC-residue samples and evaluated with respect to Cr, Cd, Cu, Pb and Zn leaching. The effect of drying of the wet APC-residue samples was particularly dramatic regarding the leaching of Cr. Drying resulted in 10-100 times more Cr leaching in both batch and columns test. Drying also affected the leaching of Cd, Cu and Pb. Initial Cd leaching was up to 100 times higher in column tests with dried APC-residue than in tests with wet residues. The effect of drying appeared to be a combination of decreasing the reduction capacity of the sample (Cr), decreasing pH (Cd, Cu) and in column tests also a wash-out of salts (probably affecting Cd and Pb). If the leaching tests are intended to mimic landfill conditions, the results of this paper suggest that the tests should be done on wet, non-dried residue samples, although this may be less practical than testing dried samples.


Neighbourhood drivability: environmental and individual characteristics associated with car use across Europe.
Car driving is a form of passive transportation associated with higher sedentary behaviour, which is associated with morbidity. The decision to drive a car is likely to be influenced by the 'drivability' of the built environment, but there is lack of scientific evidence regarding the relative contribution of environmental characteristics of car driving in Europe, compared to individual characteristics. This study aimed to determine which neighbourhood- and individual-level characteristics were associated with car driving in adults of five urban areas across Europe. Second, the study aimed to determine the percentage of variance in car driving explained by individual- and neighbourhood-level characteristics. Neighbourhood environment characteristics potentially related to car use were identified from the literature. These characteristics were subsequently assessed using a Google Street View audit and available GIS databases, in 59 administrative residential neighbourhoods in five European urban areas. Car driving (min/week) and individual level characteristics were self-reported by study participants (analytic sample n = 4258). We used linear multilevel regression analyses to assess cross-sectional associations of individual and neighbourhood-level characteristics with weekly minutes of car driving, and assessed explained variance at each level and for the total model. Higher residential density (β:-2.61, 95%CI: - 4.99; -0.22) and higher land-use mix (β:-3.73, 95%CI: - 5.61; -1.86) were significantly associated with fewer weekly minutes of car driving. At the individual level, higher age (β: 1.47, 95%CI: 0.60; 2.33), male sex (β: 43.2, 95%CI:24.7; 61.7), being employed (β:80.1, 95%CI: 53.6; 106.5) and ≥ 3 person household composition (β: 47.4, 95%CI: 20.6; 74.2) were associated with higher weekly minutes of car driving. Individual and neighbourhood characteristics contributed about equally to explained variance in minutes of weekly car driving, with 2 and 3% respectively, but total explained variance remained low. Residential density and land-use mix were neighbourhood characteristics consistently associated with minutes of weekly car driving, besides age, sex, employment and household composition. Although total explained variance was low, both individual- and neighbourhood-level characteristics were similarly important in their associations with car use in five European urban areas. This study suggests that more, higher quality, and longitudinal data are needed to increase our understanding of car use and its effects on determinants of health.


Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer.
Skeletal complications are a major cause of morbidity in men with hormone-refractory metastatic prostate cancer. These analyses were designed to identify the variables associated with a greater risk of skeletal complications. The 643 subjects in this report were participants in a randomized placebo-controlled trial to evaluate the effects of zoledronic acid on the incidence of skeletal-related events. All subjects had bone metastases and disease progression despite medical or surgical castration. The relationships between the baseline covariates and the time to the first skeletal-related event were assessed by Cox proportional hazard analyses. The serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide level was assessed as a representative specific marker of osteoblastic and osteoclastic activity, respectively. The other covariates included in the model were age, cancer duration, Eastern Cooperative Oncology Group performance status, analgesic use, and prostate-specific antigen, hemoglobin, and lactate dehydrogenase levels. Elevated BAP levels were consistently associated with a greater risk of adverse skeletal outcomes. Elevated BAP was significantly associated with a shorter time to the first skeletal-related event on multivariate analyses of the entire study population (relative risk 1.84, 95% confidence interval 1.40 to 2.43; P <0.001) and in subset analyses of the placebo and zoledronic acid groups. Elevated BAP levels were also consistently associated with adverse skeletal outcomes on multivariate analyses of the time to radiotherapy and pathologic fracture, the most common types of skeletal-related events in the study population. No other baseline variable was consistently associated with the risk of adverse skeletal outcomes. The results of our study have shown that elevated serum BAP levels are associated with a greater risk of adverse skeletal outcomes in men with hormone-refractory prostate cancer and bone metastases.


Capacity for care: meta-ethnography of acute care nurses' experiences of the nurse-patient relationship.
To synthesize evidence and knowledge from published research about nurses' experiences of nurse-patient relationships with adult patients in general, acute inpatient hospital settings. While primary research on nurses' experiences has been reported, it has not been previously synthesized. Meta-ethnography. Published literature from Australia, Europe, and North America, written in English between January 1999-October 2009 was identified from databases: CINAHL, Medline, British Nursing Index and PsycINFO. Qualitative studies describing nurses' experiences of the nurse-patient relationship in acute hospital settings were reviewed and synthesized using the meta-ethnographic method. Sixteen primary studies (18 papers) were appraised as high quality and met the inclusion criteria. The findings show that while nurses aspire to develop therapeutic relationships with patients, the organizational setting at a unit level is strongly associated with nurses' capacity to build and sustain these relationships. The organizational conditions of critical care settings appear best suited to forming therapeutic relationships, while nurses working on general wards are more likely to report moral distress resulting from delivering unsatisfactory care. General ward nurses can then withdraw from attempting to emotionally engage with patients. The findings of this meta-ethnography draw together the evidence from several qualitative studies and articulate how the organizational setting at a unit level can strongly influence nurses' capacity to build and sustain therapeutic relationships with patients. Service improvements need to focus on how to optimize the organizational conditions that support nurses in their relational work with patients.


Risk Factors for Pancreatic Stone Formation in Type 1 Autoimmune Pancreatitis: A Long-term Japanese Multicenter Analysis of 624 Patients.
Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP. Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation. Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones. The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.


Jazz improvisers' shared understanding: a case study.
To what extent and in what arenas do collaborating musicians need to understand what they are doing in the same way? Two experienced jazz musicians who had never previously played together played three improvisations on a jazz standard ("It Could Happen to You") on either side of a visual barrier. They were then immediately interviewed separately about the performances, their musical intentions, and their judgments of their partner's musical intentions, both from memory and prompted with the audiorecordings of the performances. Statements from both (audiorecorded) interviews as well as statements from an expert listener were extracted and anonymized. Two months later, the performers listened to the recordings and rated the extent to which they endorsed each statement. Performers endorsed statements they themselves had generated more often than statements by their performing partner and the expert listener; their overall level of agreement with each other was greater than chance but moderate to low, with disagreements about the quality of one of the performances and about who was responsible for it. The quality of the performances combined with the disparities in agreement suggest that, at least in this case study, fully shared understanding of what happened is not essential for successful improvisation. The fact that the performers endorsed an expert listener's statements more than their partner's argues against a simple notion that performers' interpretations are always privileged relative to an outsider's.


Identification and immunochemical location of UMP kinase from Bacillus subtilis.
Phosphorylation of CMP and UMP is accomplished in Bacillus subtilis, as in Escherichia coli, by two different enzymes exhibiting characteristic structural and catalytic properties. UMP kinase from B. subtilis is an oligomer whose activity is strictly dependent on GTP. The B. subtilis enzyme is unstable in the absence of UTP, which acts as an allosteric inhibitor. Antibodies raised against recombinant B. subtilis UMP kinase recognized the protein both in soluble extract and in immunoelectron microscopy. UMP kinase from B. subtilis has a peripheral distribution which is related most probably to its role in the synthesis of membrane sugar components and its putative role in cell division.


Evolution of the heart from bacteria to man.
This review provides an overview of the evolutionary path to the mammalian heart from the beginnings of life (about four billion years ago ) to the present. Essential tools for cellular homeostasis and for extracting and burning energy are still in use and essentially unchanged since the appearance of the eukaryotes. The primitive coelom, characteristic of early multicellular organisms ( approximately 800 million years ago), is lined by endoderm and is a passive receptacle for gas exchange, feeding, and sexual reproduction. The cells around this structure express genes homologous to NKX2.5/tinman, and gradual specialization of this "gastroderm" results in the appearance of mesoderm in the phylum Bilateria, which will produce the first primitive cardiac myocytes. Investment of the coelom by these mesodermal cells forms a "gastrovascular" structure. Further evolution of this structure in the bilaterian branches Ecdysoa (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular heart, without valves, without blood vessels or blood, but featuring a single layer of contracting mesoderm. The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system. A later innovation is the parallel circulation to the lungs, followed by the appearance of septa and the four-chambered heart in reptiles, birds, and mammals. With differentiation of the cardiac chambers, regional specialization of the proteins in the cardiac myocyte can be detected in the teleost fish and amphibians. In mammals, growth constraints are placed on the heart, presumably to accommodate the constraints of the body plan and the thoracic cavity, and adult cardiac myocytes lose the ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte innervation betrays the ancient link between the heart, the gut, and reproduction: the vagus nerve controlling heart rate emanates from centers in the central nervous system regulating feeding and affective behavior.


Subjective response to antipsychotic drugs.
Sixty-three newly admitted schizophrenic patients were given a test dose of thiothixene and their subjective response was recorded by a technician blind to clinical ratings. All patients were then treated wih thiothixene in an active milieu setting. Patients varied widely in their subjective responses. An initial dysphoric response was a powerful predictor of both immediate and eventual drug refusal. Before treatment, dysphoric responders tended to be less symptomatic and did significantly better on the Continuous Performance Test. Dysphoric responders experienced significantly more extrapyramidal symptoms following the test dose. Some dysphoric responders did have a good outcome when treated with very low doses. We recommend that patients with a history of dysphoric response be given a very low dose initially.


A label-free aptamer-based nanogap capacitive biosensor with greatly diminished electrode polarization effects.
A significant impediment to the use of impedance spectroscopy in bio-sensing is the electrode polarization effect that arises from the movement of free ions to the electrode-solution interface, forming an electrical double layer (EDL). The EDL screens the dielectric response of the bulk and its large capacitance dominates the signal response at low frequency, masking information particularly relevant for biological samples, such as molecular conformation changes and DNA hybridization. The fabrication of nanogap capacitors with electrode separation less than the EDL thickness can significantly reduce electrode polarization effects and provide enormous improvement in sensitivity due to better matching of the sensing volume with the size of the target entities. We report on the fabrication of a horizontal thin-film nanogap capacitive sensor with electrode separation of 40 nm that shows almost no electrode polarization effects when measured with water and ionic buffer solutions, thereby allowing direct quantification of their relative permittivity at low frequencies. Surface modification of the electrodes with thiol-functionalized single strand DNA aptamers transforms the device into a label-free biosensor with high sensitivity and selectivity towards the detection of a specific protein. Using this approach, we have developed a biosensor for the detection of human alpha thrombin. In addition, we also examine frequency dependent permittivity measurements on high ionic strength solutions contained within the nanogap and discuss how these support recent experimental observations of large Debye lengths. A large shift in the Debye relaxation frequency to lower frequency is also found, which is consistent with water molecules being in a rigid-like state, possibly indicating the formation of an ordered "ice-like" phase. Altogether, this work highlights the need for better understanding of fluids in confined, nanoscale geometries, from which important new applications in sensing may arise.


[Myths and beliefs surrounding breastfeeding].
The scope of this work was to analyze the main myths and beliefs surrounding breastfeeding for the theoretical-practical perspective of the various studies extant in the literature. The studies were obtained by bibliographical surveys in the main databases (Medline, Lilacs, scielo), retrieved using the key words "Breastfeeding," "Weaning," "Myths" and "Beliefs" (and their versions in English and Spanish). Books, theories, dissertations and publications in international and national organs were also consulted. It was seen that over the centuries there have been doubts surrounding the correct form of suckling newborns based on concepts that include biological aspects and socio-cultural determinants. It was seen that various myths and beliefs surrounding suckling generate either feelings of guilt, anxiety, or feelings of trust and support in the breastfeeding mother with respect to her capacity to produce breast milk. In this respect, it is necessary for healthcare professionals to understand suckling from the maternal standpoint, dispelling myths and beliefs, altering outlooks, in such a way as to comprehend the various factors present in suckling, acting in a more effective way for prolongation and maintenance of breastfeeding.