Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.
Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide. To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome. Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined. Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation. Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation). The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.


Physical activity, health, body mass index, sleeping habits and body complaints in Australian senior high school students.
Adolescents in the industrial world are becoming less physically active and are increasingly adopting a sedentary life-style in front of computers and television screens. to determine self-related health, physical activity, sleeping habits, prevalence of overweight, and body complaints in Australian senior high school students. Participants were 466 high school students aged 15-17 years enrolled in academic and vocational programs. A questionnaire was completed at two senior high schools with questions about weight and height, health, physical activity, type of physical activity/sport, intensity, sleeping habits, and possible injuries or complaints during the last three months. Seventy seven percent of the high school students participated in sports on a regular basis. Compared with vocational programs, more males and females in academic programs participated in sports (71% and 80% respectively) (p = .036). Males reported significantly better health than females (p < .0001). 65% of the study group reported body complaints during the last 3 months. A higher number of females than males reported complaints about the back (p = .007) and the hip (p = .05). Good sleep was reported in 82.1% of males and in 76.6% of females. In males, 44.3% were often sleepy in the daytime (females 56.6%, p < .01). Underweight, physical activity and good sleep are factors with significant positive effect on good health, whereas overweight is a negative factor. Proper sleep habits and higher physical activity levels should be promoted among high school students, and TV viewing time and video game use restricted. Additionally, schools should provide opportunities for young people to participate in a wider range of physical activities that address their individual needs while promoting the health benefits of engaging in regular exercise.


Relationship between nonstructural protein 1 detection and plasma virus load in Dengue patients.
We report data from a prospective observational study performed in Martinique during a co-epidemic of dengue virus serotype 2 (DENV-2) and serotype 4 (DENV-4). Among 70 serum samples from patients with DENV-2 (n = 21) or DENV-4 (n = 49) infections, 47 (67.1%) were positive for dengue nonstructural protein 1 (NS1). Antigenemia correlated with plasma virus load and was independent of immune status and the time of sampling. Increased viremia 4-6 days after onset of illness was associated with NS1 positivity, secondary infection, and severe disease. Testing for NS1 could help identify the potentially most severely ill patients during the critical phase of dengue.


Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8.
The role of cellular proteins in the replication of retroviruses, especially during virus assembly, has been partly unraveled by recent studies. Paradoxically, little is known about the route taken by retroviruses to reach the nucleus at the early stages of infection. To get insight into this stage of virus replication, we have studied the trafficking of foamy retroviruses and have previously shown that incoming viral proteins reach the microtubule organizing center (MTOC) prior to nuclear translocation of the viral genome. Here, we show that incoming viruses concentrate around the MTOC as free and structured capsids. Interestingly, the Gag protein, the scaffold component of viral capsids, targets the pericentrosomal region in transfected cells in the absence of any other viral components but in a microtubule- and dynein/dynactin-dependent manner. Trafficking of Gag towards the centrosome requires a minimal 30 amino acid coiled-coil motif in the N-terminus of the molecule. Finally, we describe a direct interaction between Gag and dynein light chain 8 that probably accounts for the specific routing of the incoming capsids to the centrosome prior to nuclear import of the viral genome.


Epidemiology, risk factors, and lifestyle modifications for gout.
Gout affects more than 1% of adults in the USA, and it is the most common form of inflammatory arthritis among men. Accumulating data support an increase in the prevalence of gout that is potentially attributable to recent shifts in diet and lifestyle, improved medical care, and increased longevity. There are both nonmodifiable and modifiable risk factors for hyperuricemia and gout. Nonmodifiable risk factors include age and sex. Gout prevalence increases in direct association with age; the increased longevity of populations in industrialized nations may contribute to a higher prevalence of gout through the disorder's association with aging-related diseases such as metabolic syndrome and hypertension, and treatments for these diseases such as thiazide diuretics for hypertension. Although gout is considered to be primarily a male disease, there is a more equal sex distribution among elderly patients. Modifiable risk factors for gout include obesity, the use of certain medications, high purine intake, and consumption of purine-rich alcoholic beverages. The increasing prevalence of gout worldwide indicates that there is an urgent need for improved efforts to identify patients with hyperuricemia early in the disease process, before the clinical manifestations of gout become apparent.


The effect of Rift Valley fever virus Clone 13 vaccine on semen quality in rams.
Rift Valley fever (RVF) is an arthropod-borne viral disease of importance in livestock and humans. Epidemics occur periodically in domestic ruminants. People in contact with infected livestock may develop disease that varies from mild flu-like symptoms to fatal viraemia. Livestock vaccination may assist in disease control. Rift Valley fever virus (RVFV) Clone 13 is a relatively new vaccine against RVF, derived from an avirulent natural mutant strain of RVFV, and has been shown to confer protective immunity against experimental infection with RVFV. The hypothesis tested in the current trial was that rams vaccinated with RVFV Clone 13 vaccine would not experience a reduction in semen quality (measured by evaluating the percentage progressively motile and percentage morphologically normal spermatozoa in successive ejaculates) relative to unvaccinated control animals. Ram lambs were screened for antibodies to RVFV using a serum neutralisation test. Animals without detectable antibodies (n = 23) were randomly allocated to either a test group (n = 12) or a control group (n = 11). Animals in the test group were vaccinated with RVFV Clone 13 vaccine. Daily rectal temperature measurements and weekly semen and blood samples were taken from all animals. Seven animals were eliminated from the statistical analysis because of potential confounding factors. Logistic regression analysis was performed on data gathered from the remaining animals to determine whether an association existed between animal group, rectal temperature and semen quality parameters. No correlation existed between the treatment group and values obtained for the semen quality parameters measured. There was no statistically significant post-vaccination decline in the percentage of live morphologically normal spermatozoa, or the percentage of progressively motile spermatozoa, either when assessed amongst all animals or when assessed within individual groups. A repeat study with a larger sample size and a more comprehensive pre-screening process may be indicated to avoid the inclusion of unsuitable animals.


Kinetic mechanism determination and analysis of metal requirement of dehydroquinate synthase from Mycobacterium tuberculosis H37Rv: an essential step in the function-based rational design of anti-TB drugs.
The number of new cases of tuberculosis (TB) arising each year is increasing globally. Migration, socio-economic deprivation, HIV co-infection and the emergence of drug-resistant strains of Mycobacterium tuberculosis, the main causative agent of TB in humans, have all contributed to the increasing number of TB cases worldwide. Proteins that are essential to the pathogen survival and absent in the host, such as enzymes of the shikimate pathway, are attractive targets to the development of new anti-TB drugs. Here we describe the metal requirement and kinetic mechanism determination of M. tuberculosis dehydroquinate synthase (MtDHQS). True steady-state kinetic parameters determination and ligand binding data suggested that the MtDHQS-catalyzed chemical reaction follows a rapid-equilibrium random mechanism. Treatment with EDTA abolished completely the activity of MtDHQS, and addition of Co(2+) and Zn(2+) led to, respectively, full and partial recovery of the enzyme activity. Excess Zn(2+) inhibited the MtDHQS activity, and isotitration microcalorimetry data revealed two sequential binding sites, which is consistent with the existence of a secondary inhibitory site. We also report measurements of metal concentrations by inductively coupled plasma atomic emission spectrometry. The constants of the cyclic reduction and oxidation of NAD(+) and NADH, respectively, during the reaction of MtDHQS was monitored by a stopped-flow instrument, under single-turnover experimental conditions. These results provide a better understanding of the mode of action of MtDHQS that should be useful to guide the rational (function-based) design of inhibitors of this enzyme that can be further evaluated as anti-TB drugs.


Buses as fire hazards: a Swedish problem only? Suggestions for fire-prevention measures.
In Sweden, approximately 6% of all human transportation is made via buses. The Swedish Board of Accident Investigation and the Swedish Rescue Services Agency have pointed out repeatedly that buses are potential fire and burn hazards, not only when involved in collisions but also in other circumstances. The number of fire incidents is increasing, especially in newer buses. In conjunction with the Swedish Rescue Services Agency, we examined some of the recent bus fires in Sweden. We did not find any casualties, but the results of our study suggest that casualties as a result of bus fires are imminent unless preventive measures are taken. We also studied experiences from previous bus fires and suggest preventive measures.


Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers.
The demonstration that dendritic cell (DC)-derived exosomes can be exploited for targeted RNAi delivery to the brain after systemic injection provides the first proof-of-concept for the potential of these naturally occurring vesicles as vehicles of drug delivery. As well as being amenable to existing in vivo targeting strategies already in use for viruses and liposomes, this novel approach offers the added advantages of in vivo safety and low immunogenicity. Fulfilment of the potential of exosome delivery methods warrants a better understanding of their biology, as well as the development of novel production, characterisation, targeting and cargo-loading nanotechnologies. Ultimately, exosome-mediated drug delivery promises to overcome important challenges in the field of therapeutics, such as delivery of drugs across otherwise impermeable biological barriers, such as the blood brain barrier, and using patient-derived tissue as a source of individualised and biocompatible therapeutic drug delivery vehicles.


Systematic review and meta-analyses of studies of glutamine supplementation in haematopoietic stem cell transplantation.
It is unclear whether supplemental glutamine is of benefit in haematopoietic stem cell transplantation (HSCT). We performed a systematic review and meta-analyses using Cochrane methodology. Seventeen randomized controlled trials (RCTs) were found. There was considerable heterogeneity between studies in terms of patient demographics and glutamine administration schedule. Many of the studies were small and scored poorly on methodological quality. Oral glutamine may reduce mucositis (average mucositis score: standard mean difference -0.38, 95% confidence interval (CI) -0.59 to -0.16) and days of opioids (mean difference -1.95 days, 95% CI -3.66 to -0.25) and GVHD (relative risk 0.42, 95% CI 0.21-0.85). Glutamine (i.v.) may reduce clinical infections (relative risk 0.75, 95% CI 0.58 to 0.97) and positive cultures (relative risk 0.72, 95% CI 0.57-0.91) but may also increase the risk of relapse (relative risk 2.91, 95% CI 1.34-6.29) but this is based on only two small studies. There was no effect of oral or i.v. glutamine on overall transplant-related mortality at day +100. In conclusion, there may be beneficial effects of glutamine in HSCT but larger, well-designed studies are required to confirm the beneficial effects and investigate possible adverse effects.


Quantitative differences in the expression of parentally-derived H-2 antigens in F1 hybrid mice affect T-cell responses.
Quantitative absorption with specific anti-H-2 sera has shown that the H-2Kb and H-2Dd antigens coded by the B10.A(5R) haplotype are expressed in about fourfold lower amount on the spleen cells of [B10.A(5R) X B10.A(2R)]F1 hybrids than on parental B10.A(5R) cells. In contrast, the H-2Kk and H-2Db antigens of B10.A(2R) are expressed equally on parental and F1 cells. These quantitative differences are reflected in cytotoxic T-cell (Tc-cell) function. Macrophage target cells from F1 mice are killed less efficiently than B10.A(5R) targets by alloreactive or H-2 restricted Tc cells specific for H-2Kb or H-2Dd, and spleen cells of F1 mice are less efficient stimulators of alloreactive Tc cells specific for B10.A(5R) H-2 antigens, whereas F1 and B10.A(2R) cells are equal as targets and stimulators for Tc cells recognizing B10.A(2R) H-2 antigens.


Dermoscopic appearance of juvenile xanthogranuloma.
Juvenile xanthogranuloma (JXG) is the commonest form of non-Langerhans cell histiocytosis and manifests as asymptomatic yellow-red papulonodules that usually occur in childhood and spontaneously regress within a year of formation. The diagnosis may be made by clinical examination alone and confirmed by histology in cases of diagnostic doubt. Here we report the use of dermoscopy in evaluating skin lesions suggestive of JXG. Three patients diagnosed as having JXG in our dermatology department over the last year showed a characteristic orange-yellow 'setting sun' appearance on dermoscopy. We therefore feel that the use of dermoscopy can be extended to include the examination of non-pigmented skin lesions, particularly in paediatric patients.


Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death.
The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis.


Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer.
There is compelling evidence for the role of natural killer (NK) cells in tumor immunosurveillance and their beneficial effects on many experimentally successful immunotherapy strategies. NK cells mediate cell contact-dependent cellular cytotoxicity and produce pro-inflammatory cytokines, but do not rearrange antigen receptors. Their activation depends on various germline-encoded receptors, including CD16, which mediates recognition of antibody-coated target cells. NK cytotoxicity is checked by a repertoire of inhibitory receptors that scan adequate expression of major histocompatibility complex class I molecules on the potential target cell. Functional cross-talk of NK and dendritic cells suggests a critical role for NK cells in the initiation and regulation of cellular immunity. Considerable knowledge on the molecular basis of NK recognition/activation contrasts with a lack of successful translational research on these matters. However, there is plenty of opportunity for targeted intervention of inhibitory/activatory surface receptors and for adoptive cell therapy with autologous or allogeneic NK cells.


Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian-human immunodeficiency virus infection in macaques.
Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian-human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV-SIV antigens merits further investigation in preventing HIV-1 infection.


New insights into disease-specific absence of complement factor H related protein C in mouse models of spontaneous autoimmune diseases.
Complement factor H (CFH) protein is an inhibitor of the alternative pathway of complement (AP) both in the fluid phase and on the surface of host cells. Mouse and human complement factor H-related (CFHR) proteins also belong to the fH family of plasma glycoproteins. The main goal of the current study was to compare the presence of mRNA for two mCFHR proteins in spontaneously developing autoimmune diseases in mice such as dense deposit disease (DDD), diabetes mellitus (DM), basal laminar deposits (BLD), collagen antibody-induced arthrits (CAIA) and systemic lupus erythematosus (SLE). Here we report for the first time that the CFHR-C mRNA was universally absent in the liver from three strains of lupus-prone mice and in a diabetic-prone mouse strain. The mRNA levels (pg/ng) for CFH and CFHR-B in MRL-lpr/lpr, at 9 wks and 23 wks were 707.2±44.4, 54.5±5.75 and 729±252.9, 74.04±22.76, respectively. The mRNA levels for CFH and CFHR-B in NZB/NZW mice, at 9 wks and 54 wks were 579.9±23.8, 58.8±1.41 and 890.3±135.2, 63.30±9.2, respectively. CFHR-C protein was absent in the circulation of MRL-lpr/lpr and NZB/NZW mice before and after the development of lupus. Similarly, mRNA and protein for CFHR-C was universally absent in liver and other organs and in the circulation of NOD mice before and after the development of DM. In contrast, the mRNAs for CFH, CFHR-B and CFHR-C were universally present in the liver from mice with and without DDD, BLD and CAIA. The levels of mRNA for CFHR-B in mice with and without BLD were ∼4 times higher than the mice with lupus. The complete absence of mRNA for CFHR-C in lupus and diabetic-prone strains indicates that polymorphic variation within the mouse CFHR family exists and raises the possibility that such variation contributes to lupus and diabetic phenotypes.


Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Correlation with Macular Function.
The purpose of this study was to investigate the relationship between the retinal pigment epithelium (RPE) and outer retina changes, expressed in terms of sub-RPE illumination (SRI) on optical-coherence tomography (OCT), and central retinal function, measured by visual acuity and focal electroretinogram (fERG), in patients with non-exudative age-related macular degeneration (neAMD). In this retrospective study, 29 eyes of 29 patients affected by early (24.14%), intermediate (41.38%), and advanced (34.48%) neAMD were evaluated. All enrolled eyes were studied with OCT to measure the total area of SRI, by using an automated standardized algorithm. Visual acuity and fERG were assessed. The area of SRI was negatively correlated with fERG amplitude (r ≤ -0.4, p ≤ 0.02) and best-corrected visual acuity (BCVA) (r ≤ 0.4, p ≤ 0.04). Our results indicate that the severity of retinal pigment epithelium and outer retina atrophy (RORA), indirectly quantified through the detection of SRI areas by commercial OCT algorithms, is correlated with central retinal dysfunction, as determined by visual acuity and fERG, supporting the combined use of structural exams and functional tests as valid tools to detect the extent of RPE and photoreceptors' disruption.


Comparison between published clinical success of direct resin composite restorations in vital posterior teeth in 1995-2005 and 2006-2016 periods.
Composites are increasing in popularity as restorative materials. This growing role indicates the necessity of studies on their clinical outcome. In this study, clinical studies published on the performance of posterior composite restorations were included except those of less than a 24-month assessment period. Results of non-vital, anterior or primary teeth and cervical single-surface restorations were also excluded. Records about composite type, number of final recall restorations, failure/survival rate, assessment period and failure reasons were analysed for each decade. Overall survival/failure rates for studies in 1995-2005 were 89.41%/10.59% and for 2006-2016 were 86.87%/13.13%, respectively. In 1995-2005, the reasons for failure were secondary caries (29.47%) and composite fracture (28.84%) with low tooth fracture (3.45%) compared with reasons of failure in 2006-2016, which were secondary caries (25.68%), composite fracture (39.07%), and tooth fracture (23.76%). An increase in incidence of composite fracture, tooth fracture and need for endodontic treatment as failure reasons was noted in the latter decade in addition to a decrease in secondary caries, postoperative sensitivity, unsatisfactory marginal adaptation and wear. The overall rates of failure showed little difference, but the causes showed a notable change. This is believed to be a reflection of increased use of composites for larger restorations and possibly changes of material characteristics.


Linking molecular diagnostics to molecular therapeutics: targeting the PI3K pathway in breast cancer.
Modulation of the signaling pathways that are aberrant in cancer cells has the potential to provide an effective nontoxic approach to patient management in a broad range of cancers. This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Support for the concept of targeting products of fusion genes found in specific cancers was first provided by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia where the RARalpha all-trans retinoic acid target is the target of multiple different chromosomal rearrangements. In breast cancer, trastuzumab, which alters the function of the HER2 proto-oncogene overexpressed in a portion of breast cancers, provides an additional example of targeting specific molecular aberrations present in cancer cells. Although the target for these signal transduction modulators is functional in normal cells, acceptable therapeutic indices sufficient to prevent tumor growth without unacceptable toxicities have been observed. Whether STI-571 and other signal transduction modulators also target the stroma, and specifically the neovasculature, in addition to the tumor remains an open question. The presence of the target in the cancer cells or in the surrounding stroma appears to be required but not sufficient for the action of molecular therapeutics. Thus, linking molecular diagnostics to identify patients where the target is amplified or activated and driving the pathophysiology of the patients' tumor to effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for breast cancer patients. This review will focus on the phosphatidylinositol 3-kinase pathway and novel molecules targeting this pathway to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast cancer.


Mortality patterns in Vietnam, 2006: Findings from a national verbal autopsy survey.
Accurate nationally representative statistics on total and cause-specific mortality in Vietnam are lacking due to incomplete capture in government reporting systems. This paper presents total and cause-specific mortality results from a national verbal autopsy survey conducted first time in Vietnam in conjunction with the annual population change survey and discusses methodological and logistical challenges associated with the implementation of a nation-wide assessment of mortality based on surveys.Verbal autopsy interviews, using the WHO standard questionnaire, were conducted with close relatives of the 6798 deaths identified in the 2007 population change survey in Vietnam. Data collectors were health staff recruited from the commune health station who undertook 3-day intensive training on VA interview. The Preston-Coale method assessed the level of completeness of mortality reporting from the population change survey. The number of deaths in each age-sex grouping is inflated according to the estimate of completeness to produce an adjusted number of deaths. Underlying causes of death were aggregated to the International Classification of Diseases Mortality Tabulation List 1. Leading causes of death were tabulated by sex for three broad age groups: 0-14 years; 15-59 years; and 60 years and above. Completeness of mortality reporting was 69% for males and 54% for females with substantial regional variation. The use of VA has resulted in 10% of deaths being classified to ill-defined among males, and 15% among females. More ill-defined deaths were reported among the 60 year or above age group. Incomplete death reporting, wide geographical dispersal of deaths, extensive travel between households, and substantial variation in local responses to VA interviews challenged the implementation of a national mortality and cause of death assessment based on surveys. Verbal autopsy can be a viable tool to identify cause of death in Vietnam. However logistical challenges limit its use in conjunction with the national sample survey. Sentinel population clusters for mortality surveillance should be tested to develop an effective and sustainable option for routine mortality and cause of death data collection in Vietnam.


Operator formulation of plane mirror systems.
A terminology limited to point objects is introduced to distinguish between finite and infinite, transparent and opaque mirrors. A basic image-producing operator is defined, and its properties are examined in detail. An operational form of the basic operator is derived, two general definitions are presented, and a formal expression for the images of a system of plane mirrors is written. Some simple systems are analyzed in detail to illustrate the applications of the theory. Finally, indication is given of possible directions for future development of the subject, and of its relationship to existing mathematical theories.


Wavelet analysis of olfactory nerve response to stimulus.
Multiunit electrophysiological activity recorded by gross electrodes from the olfactory nerve was analyzed by wavelet decomposition, a relatively new method of signal processing. The analysis was run on data from the unstimulated olfactory system as well as on data evoked in response to six different odorant stimuli. Like Fourier analysis, wavelet analysis provides a spectral decomposition of the signal. Unlike Fourier, wavelet analysis also locates the dominant spectral features in time. The output of a wavelet analysis can be further processed to enhance selected features. The increased amplitude of the nerve response evoked by stimulation was the most obvious feature, but efforts to learn from it were unproductive. The temporal pattern of receptor cell activity was much more yielding. The analysis resolved the nerve activity into three classes of events based on duration. On wavelet maps these classes of events separate out into three shifting and overlapping but distinct bands, one of which was interpreted as being associated with individual receptor cell firings and the other two as short and somewhat longer duration bursts of activity that was attributed to the synchronized firing of a group of receptor cells. This interpretation is supported by experiments in which waveforms simulating action potentials and bursts of action potentials are added to recorded data. Stimulation of the olfactory system with odorant molecules evokes a significant increase in the number of short duration bursts, and an amplitude increase that can be related to the number of receptor cells responding. Changes in the patterns of wavelet events can be associated with synchrony of cell firing, reset times for bursts of firing, and possibly other physiological dynamics. A number of differences in activity patterns with different odorants were observed, but without sufficient repeatability to allow reliable discrimination among them. While this study is clearly preliminary in that regard, it shows the potential of the wavelet method for contributing to the understanding of olfaction.


Using Electronic Health Records To Generate Phenotypes For Research.
Electronic health records contain patient-level data collected during and for clinical care. Data within the electronic health record include diagnostic billing codes, procedure codes, vital signs, laboratory test results, clinical imaging, and physician notes. With repeated clinic visits, these data are longitudinal, providing important information on disease development, progression, and response to treatment or intervention strategies. The near universal adoption of electronic health records nationally has the potential to provide population-scale real-world clinical data accessible for biomedical research, including genetic association studies. For this research potential to be realized, high-quality research-grade variables must be extracted from these clinical data warehouses. We describe here common and emerging electronic phenotyping approaches applied to electronic health records, as well as current limitations of both the approaches and the biases associated with these clinically collected data that impact their use in research. © 2018 by John Wiley & Sons, Inc.


Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations.
Thiamine pyrophosphokinase (TPK) produces thiamine pyrophosphate, a cofactor for a number of enzymes, including pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase. Episodic encephalopathy type thiamine metabolism dysfunction (OMIM 614458) due to TPK1 mutations is a recently described rare disorder. The mechanism of the disease, its phenotype and treatment are not entirely clear. We present two patients with novel homozygous TPK1 mutations (Patient 1 with p.Ser160Leu and Patient 2 with p.Asp222His). Unlike the previously described phenotype, Patient 2 presented with a Leigh syndrome like non-episodic early-onset global developmental delay, thus extending the phenotypic spectrum of the disorder. We, therefore, propose that TPK deficiency may be a better name for the condition. The two cases help to further refine the neuroradiological features of TPK deficiency and show that MRI changes can be either fleeting or progressive and can affect either white or gray matter. We also show that in some cases lactic acidosis can be absent and 2-ketoglutaric aciduria may be the only biochemical marker. Furthermore, we have established the assays for TPK enzyme activity measurement and thiamine pyrophosphate quantification in frozen muscle and blood. These tests will help to diagnose or confirm the diagnosis of TPK deficiency in a clinical setting. Early thiamine supplementation prevented encephalopathic episodes and improved developmental progression of Patient 1, emphasizing the importance of early diagnosis and treatment of TPK deficiency. We present evidence suggesting that thiamine supplementation may rescue TPK enzyme activity. Lastly, in silico protein structural analysis shows that the p.Ser160Leu mutation is predicted to interfere with TPK dimerization, which may be a novel mechanism for the disease.


Recent biogenic phosphorite: concretions in mollusk kidneys.
Phosphorite concretions have been detected in the kidneys of two widespread species of mollusks, Mercenaria mercenaria and Argopecten irradians, which have relatively high population densities. These concretions are the first documentation of the direct biogenic formation of phosphorite grains. The concretions are principally amorphous calcium phosphate, which upon being heated yields an x-ray diffraction pattern which is essentially that of chlorapatite. These concretions appear to be a normal formation of the excretory process of mollusks under reproductive, environmental, or pollutant-induced stress. Biogenic production of phosphorite concretions over long periods of time and diagenetic change from amorphous to crystalline structure, coupled with secondary enrichment, may account for the formation of some marine phosphorite desposits which are not easily explained by the chemical precipitation-replacement hypothesis.


Diffusion of surgical innovation among patients with kidney cancer.
Despite their potential benefits to patients with kidney cancer, the adoption of partial nephrectomy and laparoscopy has been gradual and asymmetric. To clarify whether this trend reflects differences in kidney cancer patients or differences in surgeon practice styles, the authors compared the magnitude of surgeon-attributable variance in the use of partial nephrectomy and laparoscopic radical nephrectomy with that attributable to patient and tumor characteristics. By using linked Surveillance, Epidemiology, and End Results-Medicare data, the authors identified a cohort of 5483 Medicare beneficiaries who underwent surgery for kidney cancer between 1997 and 2002. Two primary outcomes were defined: 1) the use of partial nephrectomy and (2) the use of laparoscopy among patients undergoing radical nephrectomy. By using multilevel models, surgeon- and patient-level contributions to observed variations in the use of partial nephrectomy and laparoscopic radical nephrectomy were estimated. Of the 5483 cases identified, 611 (11.1%) underwent partial nephrectomy (43 performed laparoscopically), and 4872 (88.9%) underwent radical nephrectomy (515 performed laparoscopically). After adjusting for patient demographics, comorbidity, tumor size, and surgeon volume, the surgeon-attributable variance was 18.1% for partial nephrectomy and 37.4% for laparoscopy. For both outcomes, the percentage of total variance attributable to surgeon factors was consistently higher than that attributable to patient characteristics. For many patients with kidney cancer, the surgery provided depends more on their surgeon's practice style than on the characteristics of the patient and his or her disease. Consequently, dismantling barriers to surgeon adoption of partial nephrectomy and laparoscopy is an important step toward improving the quality of care for patients with early-stage kidney cancer.


Information asymmetry in the Kenyan medical laboratory sector.
Important information about medical laboratory providers is not readily available to all patients, clinicians nor regulators in Kenya. This study was conducted as part of a wider project aiming to improve access to high quality diagnostics by addressing information asymmetries in the Kenyan market for laboratory services. The purpose of this study was to: 1) Gather pricing information for 49 common laboratory tests from medical laboratories in Nairobi, Kenya, noting where these prices were publicly available or withheld. 2) Assess patients' knowledge of testing information including: turnaround time, price, and test availability. This was a cross-sectional study where a mystery caller approach was used to survey 49 tests for turnaround time, price, and availability across 13 laboratories selected purposively. The mystery shopper survey was complemented by 251 patient exit interviews at two Kenyan hospitals to understand whether patients seeking laboratory tests in Nairobi had access to such information. All 251 patients were selected by convenience sampling. We noted that 85% of the private laboratories did not disclose test prices and turnaround times to their patients. There was a wide range of prices on several key tests, with private in-facility laboratories charging an average test price of 468% of the average test price in public laboratories across all the 49 tests. We also found that many patients lacked key information regarding the tests they needed: 65% did not know the purpose of the test while 41% did not know the test price at all. Under the current system, patients have limited access to information regarding the key criteria required to make a rational decision. This has a significant impact on the quality, price, and turnaround time (TAT) offered by the medical laboratories that operate in this dysfunctional market.


Premature sperm activation and defective spermatogenesis caused by loss of spe-46 function in Caenorhabditis elegans.
Given limited resources for motility, sperm cell activation must be precisely timed to ensure the greatest likelihood of fertilization. Like those of most species, the sperm of C. elegans become active only after encountering an external signaling molecule. Activation coincides with spermiogenesis, the final step in spermatogenesis, when the spherical spermatid undergoes wholesale reorganization to produce a pseudopod. Here, we describe a gene involved in sperm activation, spe-46. This gene was identified in a suppressor screen of spe-27(it132ts), a sperm-expressed gene whose product functions in the transduction of the spermatid activation signal. While spe-27(it132ts) worms are sterile at 25°C, the spe-46(hc197)I; spe-27(it132ts)IV double mutants regain partial fertility. Single nucleotide polymorphism mapping, whole genome sequencing, and transformation rescue were employed to identify the spe-46 coding sequence. It encodes a protein with seven predicted transmembrane domains but with no other predicted functional domains or homology outside of nematodes. Expression is limited to spermatogenic tissue, and a transcriptional GFP fusion shows expression corresponds with the onset of the pachytene stage of meiosis. The spe-46(hc197) mutation bypasses the need for the activation signal; mutant sperm activate prematurely without an activation signal in males, and mutant males are sterile. In an otherwise wild-type genome, the spe-46(hc197) mutation induces a sperm defective phenotype. In addition to premature activation, spe-46(hc197) sperm exhibit numerous defects including aneuploidy, vacuolization, protruding spikes, and precocious fusion of membranous organelles. Hemizygous worms [spe-46(hc197)/mnDf111] are effectively sterile. Thus, spe-46 appears to be involved in the regulation of spermatid activation during spermiogenesis, with the null phenotype being an absence of functional sperm and hypomorphic phenotypes being premature spermatid activation and numerous sperm cell defects.


Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors.
Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.


A comparative study of one implant versus two replacing a single molar.
A comparative study between one and two Brånemark implants replacing a single molar was conducted. Forty-seven individuals comprised two groups of 22 patients treated with one implant and 25 with two implants. A total of 72 implants were placed, 66 (92%) in the mandible and six (8%) in the maxilla. After the first year of function, the success rate was 99%, with only one implant lost. Between the second- and third-year follow-ups, 100% of the implants continued to function in the remaining 46 patients, giving a 3-year cumulative success rate of 99%. The marginal bone loss between 1 and 3 years of function was 0.10 mm (SD 0.20) for the group with one implant and 0.24 mm (SD 0.20) for the group with two implants. No changes were observed in the Sulcus Bleeding Index during the 3-year follow-up. Prosthesis mobility or screw loosening was the most frequent complication and was predominant in the group using one implant (48%), but was substantially reduced in the group using two implants (8%). These mechanical problems, using one implant only, seem to be preventable using a stronger screw joint (CeraOne abutment). Precise centric occlusal contact was established and maintained over the study period, which was thought to contribute to the very high success rate for the single-implant-supported molars, despite their high degree of mechanical problems. This study suggests that implant-supported molars can be effective therapy, and the results confirm the biomechanical analysis that two implants provide more advantageous support than does one.


Requirement of circadian genes for cocaine sensitization in Drosophila.
The circadian clock consists of a feedback loop in which clock genes are rhythmically expressed, giving rise to cycling levels of RNA and proteins. Four of the five circadian genes identified to date influence responsiveness to freebase cocaine in the fruit fly, Drosophila melanogaster. Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after cocaine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regulators of tyrosine decarboxylase.


Line-based, reduced memory, wavelet image compression.
This paper addresses the problem of low memory wavelet image compression. While wavelet or subband coding of images has been shown to be superior to more traditional transform coding techniques, little attention has been paid until recently to the important issue of whether both the wavelet transforms and the subsequent coding can be implemented in low memory without significant loss in performance. We present a complete system to perform low memory wavelet image coding. Our approach is "line-based" in that the images are read line by line and only the minimum required number of lines is kept in memory. There are two main contributions of our work. First, we introduce a line-based approach for the implementation of the wavelet transform, which yields the same results as a "normal" implementation, but where, unlike prior work, we address memory issues arising from the need to synchronize encoder and decoder. Second, we propose a novel context-based encoder which requires no global information and stores only a local set of wavelet coefficients. This low memory coder achieves performance comparable to state of the art coders at a fraction of their memory utilization.


Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA).
OBJECTIVE AND SOURCES: We reviewed the epidemiologic literature for PFOA. Perfluorooctanoic acid (PFOA) does not occur naturally but is present in the serum of most residents of industrialized countries (U.S. median, 4 ng/mL). Drinking water is the primary route of exposure in some populations, but exposure sources are not well understood. PFOA has been used to manufacture such products as Gore-Tex and Teflon. PFOA does not break down in the environment; the human half-life is estimated at about 3 years. PFOA is not metabolized in the body; it is not lipophilic. PFOA is not directly genotoxic; animal data indicate that it can cause several types of tumors and neonatal death and may have toxic effects on the immune, liver, and endocrine systems. Data on the human health effects of PFOA are sparse. There is relatively consistent evidence of modest positive associations with cholesterol and uric acid, although the magnitude of the cholesterol effect is inconsistent across different exposure levels. There is some but much less consistent evidence of a modest positive correlation with liver enzymes. Most findings come from cross-sectional studies, limiting conclusions. Two occupational cohort studies do not provide consistent evidence for chronic disease; both are limited by sample size and reliance on mortality data. Reproductive data have increased recently but are inconsistent, and any observed adverse effects are modest. Epidemiologic evidence remains limited, and to date data are insufficient to draw firm conclusions regarding the role of PFOA for any of the diseases of concern.


Comparison of three peripherally-inserted central catheters: pilot study.
Peripherally-inserted central catheters (PICCS) are non-tunnelled, central catheters inserted through a peripheral vein of the arm. They are 50-60 cm long and are usually made of either silicone or second-third generation polyurethane. PICCs can be used for prolonged, continuous or intermittent infusion therapies (up to 3 months) both in hospitalized patients and in patients treated as outpatients, in a hospice, or at home. When establishing a vascular service it is key to select a PICC that meets the requirements of safety, cost-effectiveness, high resistance (ability to take increasing fluid volumes with high pressure devices) and durability, and low complications rate. The complications and dwell times of three different PICCs were studied: coated polyurethane, valved silicone and power-injectable. The study was conducted at the chemotherapy suite at the author's hospital with the aim of selecting the right PICC based on low incidence of complications, resistance and enhanced dwell time. Results show a low incidence of complications and long dwell time among patients with the power-injectable PICC. Furthermore, this study demonstrated a reduction on the rate of occlusion and rupture with power-injectable PICCs, which makes them safer to use for administration of chemotherapy and other vesicant agents, as well as for the management of patients in critical care.


Evolving learnable neutral networks under changing environments with various rates of inheritance of acquired characters: comparison between Darwinian and Lamarckian evolution.
The processes of adaptation in natural organisms consist of two complementary phases: learning, occurring within each individual's lifetime, and evolution, occurring over successive generations of the population. In this article, we study the relationship between learning and evolution in a simple abstract model, where neural networks capable of learning are evolved using genetic algorithms (GAs). Individuals try to maximize their life energy by learning certain rules that distinguish between two groups of materials: food and poison. The connective weights of individuals' neural networks undergo modification, that is, certain characters will be acquired, through their lifetime learning. By setting various rates for the heritability of acquired characters, which is a motive force of Lamarckian evolution, we observe adaptational processes of populations over successive generations. Paying particular attention to behaviors under changing environments, we show the following results. Populations with lower rates of heritability not only show more stable behavior against environmental changes, but also maintain greater adaptability with respect to such changing environments. Consequently, the population with zero heritability, that is, the Darwinian population, attains the highest level of adaptation to dynamic environments.


Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway.
Phosphorylation is one of the most common forms of protein modification. The most frequent targets for protein phosphorylation in eukaryotes are serine and threonine residues, although tyrosine residues also undergo phosphorylation. Many of the currently applied methods for the detection and localization of protein phosphorylation sites are mass spectrometry-based and are biased against the analysis of tyrosine-phosphorylated residues because of the stability and low reactivity of phosphotyrosines. To overcome this lack of sensitive methods for the detection of phosphotyrosine-containing peptides, we have recently developed a method that is not affected by the more predominant threonine or serine phosphorylation within cells. It is based on the specific detection of immonium ion of phosphotyrosine at 216.043 Da and does not require prior knowledge of the protein sequence. In this report, we describe the first application of this new method in a proteomic strategy. Using anti-phosphotyrosine antibodies for immunoprecipitation and one-dimensional gel electrophoresis, we have identified 10 proteins in the epidermal growth factor receptor signaling pathway, of which 8 have been shown previously to be involved in epidermal growth factor signaling. Most importantly, in addition to several known tyrosine phosphorylation sites, we have identified five novel sites on SHIP-2, Hrs, Cbl, STAM, and STAM2, most of which were not predicted to be phosphorylated. Because of its sensitivity and selectivity, this approach will be useful in proteomic approaches to study tyrosine phosphorylation in a number of signal transduction pathways.


Deactivation of snares by wild chimpanzees.
Snare injuries to chimpanzees (Pan troglodytes) have been reported at many study sites across Africa, and in some cases cause the death of the ensnared animal. However, very few snare injuries have been reported concerning the chimpanzees of Bossou, Guinea. The rarity of snare injuries in this study group warrants further consideration, given the exceptionally close proximity of the Bossou chimpanzees to human settlements and the widespread practice of snare hunting in the area. Herein we report a total of six observations of chimpanzees attempting to break and deactivate snares, successfully doing so on two of these occasions. We observed the behavior in 5 males, ranging in age from juveniles to adults. We argue that such active responses to snares must be contributing to the rarity of injuries in this group. Based on our observations, we suggest that the behavior has transmitted down the group. Our research team at Bossou continues to remove snares from the forest, but the threat of ensnarement still remains. We discuss potential ways to achieve a good balance between human subsistence activities and the conservation of chimpanzees at Bossou, which will increasingly be an area of great concern in the future.


HIV-1 Transmission Patterns Within and Between Risk Groups in Coastal Kenya.
HIV-1 transmission patterns within and between populations at different risk of HIV-1 acquisition in Kenya are not well understood. We investigated HIV-1 transmission networks in men who have sex with men (MSM), injecting drug users (IDU), female sex workers (FSW) and heterosexuals (HET) in coastal Kenya. We used maximum-likelihood and Bayesian phylogenetics to analyse new (N = 163) and previously published (N = 495) HIV-1 polymerase sequences collected during 2005-2019. Of the 658 sequences, 131 (20%) were from MSM, 58 (9%) IDU, 109 (17%) FSW, and 360 (55%) HET. Overall, 206 (31%) sequences formed 61 clusters. Most clusters (85%) consisted of sequences from the same risk group, suggesting frequent within-group transmission. The remaining clusters were mixed between HET/MSM (7%), HET/FSW (5%), and MSM/FSW (3%) sequences. One large IDU-exclusive cluster was found, indicating an independent sub-epidemic among this group. Phylodynamic analysis of this cluster revealed a steady increase in HIV-1 infections among IDU since the estimated origin of the cluster in 1987. Our results suggest mixing between high-risk groups and heterosexual populations and could be relevant for the development of targeted HIV-1 prevention programmes in coastal Kenya.


Polyacrylamide gel electrophoresis.
Polyacrylamide gel electrophoresis (PAGE) provides a versatile, gentle, high resolution method for fractionation and physical-chemical characterization of molecules on the basis of size, conformation, and net charge. The polymerization reaction can be rigorously controlled to provide uniform gels of reproducible, measurable pore size over a wide range. This makes it possible to obtain reproducible relative mobility (Rf) values as physical-chemical constants. Application and extension of Ogston's (random fiber) model for a gel allows for calculation of molecular volume, surface area, or radius, free mobility, and valence from RJ measurements at several gel concentrations, to calculate gel concentration for optimal resolution, and to predict behavior of macromolecules on gel gradients by computerized methods. Extension of classical moving boundary theory has been used to generate multiphasic buffer systems (providing selective stacking, unstacking, restacking, and preparative steady-state-stacking) with known operating characteristics for any pH at 0 degrees and 25 degrees C. A general strategy for isolation of macromolecules and for macromolecular mapping has been developed. Preparative scale PAGE is operational for milligram loads and feasible for gram quantities.


Chemical inhibition of N-WASP by stabilization of a native autoinhibited conformation.
Current drug discovery efforts focus primarily on proteins with defined enzymatic or small molecule binding sites. Autoregulatory domains represent attractive alternative targets for small molecule inhibitors because they also occur in noncatalytic proteins and because allosteric inhibitors may avoid specificity problems inherent in active site-directed inhibitors. We report here the identification of wiskostatin, a chemical inhibitor of the neural Wiskott-Aldrich syndrome protein (N-WASP). Wiskostatin interacts with a cleft in the regulatory GTPase-binding domain (GBD) of WASP in the solution structure of the complex. Wiskostatin induces folding of the isolated, unstructured GBD into its autoinhibited conformation, suggesting that wiskostatin functions by stabilizing N-WASP in its autoinhibited state. The use of small molecules to bias conformational equilibria represents a potentially general strategy for chemical inhibition of autoinhibited proteins, even in cases where such sites have not been naturally evolved in a target.


Maternal agency influences the prevalence of diarrhea and acute respiratory tract infections among young Indonesian children.
To examine the relationship between measures of mother's caretaking, practice and individual agency on acute diarrhea and respiratory tract infections (ARTIs) of Indonesian children. Using population-based household data from the Indonesian Demographic Health Surveys for 2002-2003 (n = 9,151 children) and 2007 (n = 9,714 children), we selected 28 indicators related to mother' caretaking, and applied principal component analysis to derive indices for access to care, practice and experience, and agency. The association between index quartiles (level 1-4) and the prevalence of diarrhea and ARTIs in the youngest child <5 years of age was assessed with multivariate logistic regression adjusting for socioeconomic status, residence type, mother's age and education, family size, child's age and sex, immunization status and received vitamin A supplementation. Moderate levels (level 3) of practice and experience were associated with decreased diarrheal risk (adjusted OR 0.86, 95 % CI 0.75-0.98), but not for ARTIs. Children of mothers with higher levels (level 4) of agency were protected against both diarrhea (adjusted OR 0.68, 95 % CI 0.60-0.77) and ARTIs (adjusted OR 0.77, 95 % CI 0.66-0.91). Stratified analyses with child's age and mother's education, and tests of interaction, showed that agency had a stronger effect on diarrhea and ARTIs prevalence in children <2 years of age. Maternal caretaking, especially agency, is strongly associated with lower prevalence of diarrhea and ARTIs in younger children. Interventions specifically designed to promote maternal autonomy and decision-making may lead to improved child health.


The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis.
Centrosomes consist of a pair of centrioles surrounded by an amorphous pericentriolar material (PCM). Proteins that contain a Pericentrin/AKAP450 centrosomal targeting (PACT) domain have been implicated in recruiting several proteins to the PCM. We show that the only PACT domain protein in Drosophila (the Drosophila pericentrin-like protein [D-PLP]) is associated with both the centrioles and the PCM, and is essential for the efficient centrosomal recruitment of all six PCM components that we tested. Surprisingly, however, all six PCM components are eventually recruited to centrosomes during mitosis in d-plp mutant cells, and mitosis is not dramatically perturbed. Although viable, d-plp mutant flies are severely uncoordinated, a phenotype usually associated with defects in mechanosensory neuron function. We show that the sensory cilia of these neurons are malformed and the neurons are nonfunctional in d-plp mutants. Moreover, the flagella in mutant sperm are nonmotile. Thus, D-PLP is essential for the formation of functional cilia and flagella in flies.


Power outputs of a machine squat-jump across a spectrum of loads.
The load that maximizes mechanical power output (Pmax) has received considerable research attention owing to its perceived importance to training prescription. However, it may be that identifying Pmax is of little importance if the difference in power output about Pmax is insubstantial. Additionally, comparing the effect of load on power output between studies is problematic due to various methodological differences. The purpose of this study therefore was to quantify the concentric power output for a machine squat-jump across a spectrum of loads (10-100% of 1 repetition maximum [1RM]). To estimate Pmax load and proximate loads a quadratic was fitted to the power output (Watts) and load (% of 1RM) of 18 well-trained rugby athletes. Pmax for peak and mean power output occurred at 21.6 +/- 7.1% of 1RM (mean +/- SD) and 39.0 +/- 8.6% of 1RM, respectively. A 20% change in load either side of the maximum resulted in a mean decrease of only 9.9% (90% confidence limits +/-2.4%) and 5.4% (+/-0.9%) in peak and mean power respectively; standard deviations about these means (representing individual differences in the decrease) were 6.0% and 2.1%, respectively (90% confidence limits x//1.34). It appears that most athletes have a broad peak in their power profile for peak or mean power. The preoccupation of identifying one load for maximizing power output would seem less meaningful than many practitioners and scientists believe.


Conventions and workflows for using Situs.
Situs is a modular program package for the multi-scale modeling of atomic resolution structures and low-resolution biophysical data from electron microscopy, tomography or small-angle X-ray scattering. This article provides an overview of recent developments in the Situs package, with an emphasis on workflows and conventions that are important for practical applications. The modular design of the programs facilitates scripting in the bash shell that allows specific programs to be combined in creative ways that go beyond the original intent of the developers. Several scripting-enabled functionalities, such as flexible transformations of data type, the use of symmetry constraints or the creation of two-dimensional projection images, are described. The processing of low-resolution biophysical maps in such workflows follows not only first principles but often relies on implicit conventions. Situs conventions related to map formats, resolution, correlation functions and feature detection are reviewed and summarized. The compatibility of the Situs workflow with CCP4 conventions and programs is discussed.


Comparative studies of epibatidine derivatives [18F]NFEP and [18F]N-methyl-NFEP: kinetics, nicotine effect, and toxicity.
We have previously shown that [18F]norchlorofluoroepibatidine ([18F]NFEP) would be an ideal radiotracer for positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChR); however, its high toxicity is a limiting factor for human studies. We, therefore, synthesized its N-methyl derivative ([18F]N-Me-NFEP) and carried out comparative studies. The distribution volumes for different brain regions were higher for [18F]N-Me-NFEP than those for [18F]NFEP (average: 52.5+/-0.9 vs. 36.4+/-0.7 for thalamus), though the distribution volume (DV) ratios were similar (3.93+/-0.27 vs. 3.65+/-0.19 for thalamus to cerebellum). Treatment with nicotine reduced the binding of both radiotracers. Toxicology studies in awake rats showed that N-methyl-NFEP has a lower mortality (0 vs. 30%) and smaller effect on plasma catecholamines than NFEP at a dose of 1.5 microg/kg. However, marked alterations in cardiorespiratory parameters were observed after injection of N-methyl-NFEP (0.5 microg/kg, IV) to an awake dog. Our results suggest that although the binding characteristics of [18F]NFEP and [18F]N-Me-NFEP appear to be ideally suited for PET imaging studies of the human brain, their relatively small safety margin will limit their use in humans.


Photoinduced Covalent Irreversible Inactivation of Proline Dehydrogenase by S-Heterocycles.
Proline dehydrogenase (PRODH) is a flavoenzyme that catalyzes the first step of proline catabolism, the oxidation of l-proline to Δ1-pyrroline-5-carboxylate. PRODH has emerged as a cancer therapy target because of its involvement in the metabolic reprogramming of cancer cells. Here, we report the discovery of a new class of PRODH inactivator, which covalently and irreversibly modifies the FAD in a light-dependent manner. Two examples, 1,3-dithiolane-2-carboxylate and tetrahydrothiophene-2-carboxylate, have been characterized using X-ray crystallography (1.52-1.85 Å resolution), absorbance spectroscopy, and enzyme kinetics. The structures reveal that in the dark, these compounds function as classical reversible, proline analogue inhibitors. However, exposure of enzyme-inhibitor cocrystals to bright white light induces decarboxylation of the inhibitor and covalent attachment of the residual S-heterocycle to the FAD N5 atom, locking the cofactor into a reduced, inactive state. Spectroscopic measurements of the inactivation process in solution confirm the requirement for light and show that blue light is preferred. Enzyme activity assays show that the rate of inactivation is enhanced by light and that the inactivation is irreversible. We also demonstrate the photosensitivity of cancer cells to one of these compounds. A possible mechanism is proposed involving photoexcitation of the FAD, while the inhibitor is noncovalently bound in the active site, followed by electron transfer, decarboxylation, and radical combination steps. Our results could lead to the development of photopharmacological drugs targeting PRODH.


Cross-sectional survey of women in Taiwan with first-degree relatives with osteoporosis: knowledge, health beliefs, and preventive behaviors.
No previous investigation has explored preventive behaviors among women with First-Degree Relatives (FDRs) diagnosed with osteoporosis, particularly Asian women. This study investigates osteoporosis knowledge, health beliefs and preventive behaviors of women with a family history of osteoporosis, and the different knowledge and health beliefs regarding preventive behaviors of women with such a history. Women were recruited at a large public health center in northern Taiwan. A questionnaire was administered to women with FDRs with osteoporosis with a focus on osteoporosis knowledge, health beliefs and preventive behaviors. Descriptive analysis was initially conducted. Correlation and differences between demographics, knowledge, health beliefs and preventive behaviors were rated for continuous variables, and the chi2 test was performed for categorical variables. A total of 251 who women satisfied the sampling criteria were invited to engage in the study. Two hundred and one women agreed to take part in the study, and the participation rate was around 80%. This work stresses the insufficiency of information on osteoporosis, constraining beliefs and ignorance of healthy preventive behaviors among women with FDRs with osteoporosis. Overall, the likelihood that women would take positive preventive behaviors is associated with their demographics and knowledge. The variables most strongly correlated with preventive behaviors for community-dwelling women are, in order, knowledge, number of children, educational level, knowledge of osteoporosis, experience of bone density examination, and whether or not women believed they had kyphosis. The results of this work can be applied to provide effective implementation guidelines for preventing osteoporosis, especially for women with a family history of the disease.


The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955-1985.
To describe trends in the epidemiology of rheumatoid arthritis (RA) over a period of 30 years in a population-based cohort. An inception cohort of Rochester, Minnesota residents who were > or =35 years of age and had RA (as defined by the 1987 American College of Rheumatology criteria for RA) first diagnosed between January 1, 1955 and January 1, 1985 was assembled and followed up until January 1, 1995. Incidence rates were age- and sex-adjusted to the 1970 US white population. Prevalence of RA in this cohort was estimated on January 1, 1985. A birth-cohort analysis was performed by calculating and comparing incidence rates in each of 16 birth cohorts. Of the 425 Rochester residents who fulfilled the inclusion criteria, there were 113 men (26.6%) and 312 women (73.4%), with a mean age at diagnosis of 60.2 years. The mean followup time was 15.1 years. The overall age- and sex-adjusted annual incidence of RA among Rochester, Minnesota residents > or =35 years of age (1955-1985) was 75.3 per 100,000 population (95% confidence interval 68.0-82.5). This incidence was approximately double in women compared with that in men and increased steadily with age, until age 85, after which the incidence of RA decreased. Secular trends in the incidence of RA over the entire study period were demonstrated. The overall prevalence of RA on January 1, 1985 was approximately 1%. The birth-cohort analysis showed peak incidence rates in the 1880-1895 birth cohorts. The epidemiology of RA is dynamic. The findings in this study lend further support to the hypothesis of a host-environment interaction in the pathogenesis of RA.


Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.
Structural MRI of volunteers deemed "normal" following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as "incidental findings." Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as "normal variants" to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.


I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
The intracellular loops that interlink the four transmembrane domains of Ca(2+)- and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I-II loop) in high voltage-activated (HVA) Ca(2+) channels possesses the binding site for Ca(v)beta subunits and plays significant roles in channel function, including trafficking the alpha(1) subunits of HVA channels to the plasma membrane and channel gating. Although there is considerable divergence in the primary sequence of the I-II loop of Ca(v)1/Ca(v)2 HVA channels and Ca(v)3 LVA/T-type channels, evidence for a regulatory role of the I-II loop in T-channel function has recently emerged for Ca(v)3.2 channels. In order to provide a comprehensive view of the role this intracellular region may play in the gating and surface expression in Ca(v)3 channels, we have performed a structure-function analysis of the I-II loop in Ca(v)3.1 and Ca(v)3.3 channels using selective deletion mutants. Here we show the first 60 amino acids of the loop (post IS6) are involved in Ca(v)3.1 and Ca(v)3.3 channel gating and kinetics, which establishes a conserved property of this locus for all Ca(v)3 channels. In contrast to findings in Ca(v)3.2, deletion of the central region of the I-II loop in Ca(v)3.1 and Ca(v)3.3 yielded a modest increase (+30%) and a reduction (-30%) in current density and surface expression, respectively. These experiments enrich our understanding of the structural determinants involved in Ca(v)3 function by highlighting the unique role played by the intracellular I-II loop in Ca(v)3.2 channel trafficking, and illustrating the prominent role of the gating brake in setting the slow and distinctive slow activation kinetics of Ca(v)3.3.


Improving medical student recruitment to neurosurgery.
Neurosurgery seeks to attract the best and brightest medical students; however, there is often a lack of early exposure to the field, among other possible barriers. The authors sought to identify successful practices that can be implemented to improve medical student recruitment to neurosurgery. United States neurosurgery residency program directors were surveyed to determine the number of medical student rotators and medical students matching into a neurosurgery residency from their programs between 2010 and 2016. Program directors were asked about the ways their respective institutions integrated medical students into departmental clinical and research activities. Complete responses were received from 30/110 institutions. Fifty-two percent of the institutions had neurosurgery didactic lectures for 1st- and 2nd-year medical students (MS1/2), and 87% had didactics for MS3/4. Seventy-seven percent of departments had a neurosurgery interest group, which was the most common method used to integrate medical students into the department. Other forms of outreach included formal mentorship programs (53%), lecture series (57%), and neurosurgery anatomy labs (40%). Seventy-three percent of programs provided research opportunities to medical students, and 57% indicated that the schools had a formal research requirement. On average, 3 medical students did a rotation in each neurosurgery department and 1 matched into neurosurgery each year. However, there was substantial variability among programs. Over the 2010-2016 period, the responding institutions matched as many as 4% of the graduating class into neurosurgery per year, whereas others matched 0%-1%. Departments that matched a greater (≥ 1% per year) number of medical students into neurosurgery were significantly more likely to have a neurosurgery interest group and formal research requirements. A greater percentage of high-matching programs had neurosurgery mentorship programs, lecture series, and cadaver training opportunities compared to the other institutions. In recent decades, the number of applicants to neurosurgery has decreased. A major deterrent may be the delayed exposure of medical students to neurosurgery. Institutions with early preclinical exposure, active neurosurgery interest groups, research opportunities, and strong mentorship recruit and match more students into neurosurgery. Implementing such initiatives on a national level may increase the number of highly qualified medical students pursuing neurosurgery.


Palatable Food Dampens the Long-Term Behavioral and Endocrine Effects of Juvenile Stressor Exposure but May Also Provoke Metabolic Syndrome in Rats.
The juvenile period is marked by a reorganization and growth of important brain regions including structures associating with reward seeking behaviors such as the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are impacted by stressors during the juvenile period and may lead to a predisposition to stress induced psychopathology and abnormal development of brain reward systems. Like in humans, adult rodents engage certain coping mechanisms such as increases in the consumption of calorie-rich palatable foods to reduce stress, but this behavior can lead to obesity and metabolic disorders. In this study, we examined whether stressors during the juvenile period led to increased caloric intake when a palatable diet was accessible, and whether this diet attenuated adult stress responses. In addition, we examined if the stress buffering effects produced by the palatable diet were also accompanied by an offset propensity towards obesity, and by alterations in mRNA expression of dopamine (DA) receptors in the NA and PFC in adulthood. To this end, juvenile male Wistar rats underwent episodic stressor exposure (forced swim, elevated platform stress and restraint) on postnatal days (PD) 27-29 and received access to regular chow or daily limited access to a palatable diet until adulthood. At the age of 2 months, rats were tested on a social interaction test that screens for anxiety-like behaviors and their endocrine responses to an acute stressor. Animals were sacrificed, and their brains processed to detect differences in DA receptor subtype expression in the PFC and NA using qPCR. Results showed that rats that were stressed during the juvenile period displayed higher social anxiety and a sensitized corticosterone response as adults and these effects were attenuated by access to the palatable diet. Nevertheless, rats that experienced juvenile stress and consumed a palatable diet showed greater adiposity in adulthood. Interestingly, the same group displayed greater mRNA expression of DA receptors at the NA. This suggests that access to a palatable diet mitigates the behavioral and endocrine effects of juvenile stressor exposure in adulthood, but at the cost of metabolic imbalances and a sensitized dopaminergic system.


Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance.
Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.


Complementary studies of lipid membrane dynamics using iSCAT and super-resolved fluorescence correlation spectroscopy.
Observation techniques with high spatial and temporal resolution, such as single-particle tracking based on interferometric scattering (iSCAT) microscopy, and fluorescence correlation spectroscopy applied on a super-resolution STED microscope (STED-FCS), have revealed new insights of the molecular organization of membranes. While delivering complementary information, there are still distinct differences between these techniques, most prominently the use of fluorescent dye tagged probes for STED-FCS and a need for larger scattering gold nanoparticle tags for iSCAT. In this work, we have used lipid analogues tagged with a hybrid fluorescent tag-gold nanoparticle construct, to directly compare the results from STED-FCS and iSCAT measurements of phospholipid diffusion on a homogeneous supported lipid bilayer (SLB). These comparative measurements showed that while the mode of diffusion remained free, at least at the spatial (>40 nm) and temporal (50 ⩽ t ⩽ 100 ms) scales probed, the diffussion coefficient was reduced by 20- to 60-fold when tagging with 20 and 40 nm large gold particles as compared to when using dye tagged lipid analogues. These FCS measurements of hybrid fluorescent tag-gold nanoparticle labeled lipids also revealed that commercially supplied streptavidin-coated gold nanoparticles contain large quantities of free streptavidin. Finally, the values of apparent diffusion coefficients obtained by STED-FCS and iSCAT differed by a factor of 2-3 across the techniques, while relative differences in mobility between different species of lipid analogues considered were identical in both approaches. In conclusion, our experiments reveal that large and potentially cross-linking scattering tags introduce a significant slow-down in diffusion on SLBs but no additional bias, and our labeling approach creates a new way of exploiting complementary information from STED-FCS and iSCAT measurements.


A fault tree model to assess probability of contaminant discharge from shipwrecks.
Shipwrecks on the sea floor around the world may contain hazardous substances that can cause harm to the marine environment. Today there are no comprehensive methods for environmental risk assessment of shipwrecks, and thus there is poor support for decision-making on prioritization of mitigation measures. The purpose of this study was to develop a tool for quantitative risk estimation of potentially polluting shipwrecks, and in particular an estimation of the annual probability of hazardous substance discharge. The assessment of the probability of discharge is performed using fault tree analysis, facilitating quantification of the probability with respect to a set of identified hazardous events. This approach enables a structured assessment providing transparent uncertainty and sensitivity analyses. The model facilitates quantification of risk, quantification of the uncertainties in the risk calculation and identification of parameters to be investigated further in order to obtain a more reliable risk calculation.


Identification of cleavage sites and substrate proteins for two mitochondrial intermediate peptidases in Arabidopsis thaliana.
Most mitochondrial proteins contain an N-terminal targeting signal that is removed by specific proteases following import. In plant mitochondria, only mitochondrial processing peptidase (MPP) has been characterized to date. Therefore, we sought to determine the substrates and cleavage sites of the Arabidopsis thaliana homologues to the yeast Icp55 and Oct1 proteins, using the newly developed ChaFRADIC method for N-terminal protein sequencing. We identified 88 and seven putative substrates for Arabidopsis ICP55 and OCT1, respectively. It was determined that the Arabidopsis ICP55 contains an almost identical cleavage site to that of Icp55 from yeast. However, it can also remove a far greater range of amino acids. The OCT1 substrates from Arabidopsis displayed no consensus cleavage motif, and do not contain the classical -10R motif identified in other eukaryotes. Arabidopsis OCT1 can also cleave presequences independently, without the prior cleavage of MPP. It was concluded that while both OCT1 and ICP55 were probably acquired early on in the evolution of mitochondria, their substrate profiles and cleavage sites have either remained very similar or diverged completely.


Hempseed in food industry: Nutritional value, health benefits, and industrial applications.
Hemp (Cannabis sativa L.) seeds have been consumed in Asian communities since prehistoric times. Recently, Australia, Canada, and the United States have legalized the cultivation and consumption of hempseed at low (<0.3%) tetrahydrocannabinol levels, and there's a growing interest in hempseed due to its nutritional value and pharmaceutical potential. This review aims to summarize the chemical composition, nutritional value, and potential health benefits of hempseed, as researched via in vitro and in vivo trials. The application of hempseed in the food industry is limited due to its poor performance on some functional properties, so the latest processing methods developed to improve these properties were compared. Additionally, manufacturing technologies incorporating hemp seeds into existing food products are also elaborated. This review would promote further in-depth research on this recently approved food resources and maximize its utilization in new food product development.


Benzodiazepine and Z-drug Prescribing for Elderly People in a General Hospital: A Complete Audit Cycle.
Use of benzodiazepines and Z-drugs in the elderly is associated with adverse outcomes such as increased risk of falls and fractures and cognitive impairment. We aimed to assess the prescribing practice of benzodiazepine and Z-drugs in those aged over 65 years in a general hospital against evidence based standards and to examine the effects of multidisciplinary feedback, as well as determine the prevalence of usage. All case-notes and medication charts of patients over the age of sixty five on surgical and medical wards in Sligo General Hospital (SGH) were retrieved and analysed over a two-day period in 2008. Data was collected in relation to benzodiazepine and Z-drug prescribing. We followed up on this initial data collection by screening discharge summaries at six weeks to assess benzodiazepine and Z-drug prescribing on discharge. Audit results were disseminated together with consensus guidelines on the prescribing of these medications in older adult population to all general practitioners in County Sligo. Educational sessions were held for both doctors and nurses in SGH. The audit cycle was completed by a re-audit of benzodiazepine and Z-drug prescribing six months from original study using identical methods. We found a high prevalence of benzodiazepine and Z-drug use in original audit, 54% (38/70) of the group audited. The prevalence fell to 46% (32/70) at the re-audit post intervention. This result was not statistically significant. The percentage of patients commenced on benzodiazepine and Z-drugs prior to admission fell from 36% (25/70) at the initial audit to 23% (16/70) at the re-audit. Prescribing practices were not in keeping with consensus guidelines as highlighted by this relatively basic audit cycle. Multidisciplinary feedback and letters to GPs resulted in some reduction in the number of patients prescribed benzodiazepines and Z-drugs. Ongoing educational strategies aimed at relevant health care workers with regular audit of medication use within the general hospital setting is pertinent to further improve prescribing practice.


Tooth brushing, oil pulling and tissue regeneration: A review of holistic approaches to oral health.
Even though dentistry was not a specialized branch of Ayurveda, it is included in its Shalakya Tantra (system of surgery). Problems such as deformities of the oral cavity, plaques and infections were managed in ancient India. Traditional medicine can treat various infectious and chronic conditions. Research has shown that all kinds of chewing sticks described in ancient Ayurveda texts have medicinal and anti-cariogenic properties. Its oil pulling (Kaval, Gandush) practice is claimed to cure about 30 systemic diseases. Amla (Emblic myrobalan), is a general rebuilder of oral health. Bilberry fruit (Vaccinium myrtillus) and hawthorn berry (Crateagus oxycanthus) stabilize collagen, strengthening the gum tissue. Liquorice root (Glycyrrhiza glabral) promotes anti-cavity action, reduces plaque, and has an antibacterial effect. Use of safe, quality products and practices should be ensured based on available evidence if traditional medicine is to be acknowledged as part of primary health care. Scientific validations of the Ayurveda dental health practices could justify their incorporation into modern dental care. Publicity of these techniques using appropriate media would benefit the general population by giving more confidence in the ancient practices, thus preventing tooth decay and loss.


Assessment of Regional Methane Emission Inventories through Airborne Quantification in the San Francisco Bay Area.
This study derives methane emission rates from 92 airborne observations collected over 23 facilities including 5 refineries, 10 landfills, 4 wastewater treatment plants (POTWs), 2 composting operations, and 2 dairies in the San Francisco Bay Area. Emission rates are measured using an airborne mass-balance technique from a low-flying aircraft. Annual measurement-based sectorwide methane emissions are 19,000 ± 2300 Mg for refineries, 136,700 ± 25,900 Mg for landfills, 11,900 ± 1,500 Mg for POTWs, and 11,100 ± 3,400 Mg for composting. The average of measured emissions for each refinery ranges from 4 to 23 times larger than the corresponding emissions reported to regulatory agencies, while measurement-derived landfill and POTW estimates are approximately twice the current inventory estimates. Significant methane emissions at composting facilities indicate that a California mandate to divert organics from landfills to composting may not be an effective measure for mitigating methane emissions unless best management practices are instituted at composting facilities. Complementary evidence from airborne remote sensing imagery indicates atmospheric venting from refinery hydrogen plants, landfill working surfaces, composting stockpiles, etc., to be among the specific source types responsible for the observed discrepancies. This work highlights the value of multiple measurement approaches to accurately estimate facility-scale methane emissions and perform source attribution at subfacility scales to guide and verify effective mitigation policy and action.


Theory of electron, phonon and spin transport in nanoscale quantum devices.
At the level of fundamental science, it was recently demonstrated that molecular wires can mediate long-range phase-coherent tunnelling with remarkably low attenuation over a few nanometre even at room temperature. Furthermore, a large mean free path has been observed in graphene and other graphene-like two-dimensional materials. These create the possibility of using quantum and phonon interference to engineer electron and phonon transport through nanoscale junctions for a wide range of applications such as molecular switches, sensors, piezoelectricity, thermoelectricity and thermal management. To understand transport properties of such devices, it is crucial to calculate their electronic and phononic transmission coefficients. The aim of this tutorial article is to outline the basic theoretical concepts and review the state-of-the-art theoretical and mathematical techniques needed to treat electron, phonon and spin transport in nanoscale molecular junctions. This helps not only to explain new phenomenon observed experimentally but also provides a vital design tool to develop novel nanoscale quantum devices.


Somatization, anxiety and depression as measures of health-related quality of life of children/adolescents with cancer.
This descriptive study of health-related quality of life of children with cancer compared children/adolescents', parents' and teachers' ratings for somatization, depression and anxiety to determine if there were significant correlations among respondent scores. In addition, the percentage of agreement among respondents and significant differences based on age, gender, use of cranial radiation and treatment status were measured. Forty-three children/adolescents with cancer, currently receiving therapy for at least 1 year or who had completed therapy for no more than 3 years (excluding children who had received bone marrow transplants or who had brain tumors), were recruited, with a parent and teacher, from 3 university medical centers. The Behavioral Assessment System for Children questionnaires for children/adolescents, parents and teachers were used. Parents reported a higher level of depression for the children/adolescents with cancer than did the teachers or the children/adolescents themselves. Parents reported a higher level of anxiety for the children/adolescents than did the teachers. High positive correlations were found among scores from parents and teachers and among scores from parents and children/adolescents for the anxiety and depression but not somatization subscales. Children/adolescents and teachers had high, positively correlated scores only for the depression subscale. High, positive correlations were found between somatization, anxiety and depression within each group of respondents. A significant percentage of agreement between all respondents on ratings for at-risk status was obtained only for the depression subscale. Age was the only variable found to have an influence on scores and only for the anxiety subscale.