Standard information on environmental exposure linked to data on cancer patients, with a brief review of the literature.
A review of national resources presently available for linking cancer morbidity and mortality data with information on environmental factors is presented. Additional sources of data on exposure, obtained directly from the patient or from his/her hospital record, are discussed. At the patient level, an interview questionnaire records standardized data on residential and occupational experiences and on a variety of life-style factors such as smoking, alcohol, nutrition, medication, and exercise. At the hospital level, a simple model "exposure registry" is presented which, at minimal cost, would facilitate the collection of limited data on smoking and employment (occupation/business) from the in-patient hospital admission form and from the medical and nursing notes in the patient's record. Both of these instruments represent efforts toward the development of standardized data sets on environmental and personal exposures which would constitute valuable additions to data already collected by the worldwide network of cancer registries.


Formation of basement membranes in the embryonic kidney: an immunohistological study.
Specific antibodies to laminin, type IV collagen, basement-membrane proteoglycan, and fibronectin have been used in immunofluorescence microscopy to study the development of basement membranes of the embryonic kidney. Kidney tubules are known to form from the nephrogenic mesenchyme as a result of an inductive tissue interaction. This involves a change in the composition of the extracellular matrix. The undifferentiated mesenchyme expresses in the composition of the extracellular matrix. The undifferentiated mesenchyme expresses fibronectin but no detectable laminin, type IV collagen, or basement-membrane proteoglycan. During the inductive interaction, basement-membrane specific components (laminin, type IV collagen, basement membrane proteoglycan) become detectable in the induced area, whereas fibronectin is lost. While the differentiation to epithelial cells of the kidney requires an inductive interaction, the development of the vasculature seems to involve an ingrowth of cells which throughout development deposits basement-membrane specific components, as well as fibronectin. These cells form the endothelium and possibly also the mesangium of the glomerulus, and contribute to the formation of the glomerular basement membrane. An analysis of differentiation of the kidney mesenchyme in vitro in the absence of circulation supports these conclusions. Because a continuity with vasculature is required for glomerular endothelial cell differentiation, it is possible that these cells are derived from outside vasculature.


Excemplify: a flexible template based solution, parsing and managing data in spreadsheets for experimentalists.
In systems biology, quantitative experimental data is the basis of building mathematical models. In most of the cases, they are stored in Excel files and hosted locally. To have a public database for collecting, retrieving and citing experimental raw data as well as experimental conditions is important for both experimentalists and modelers. However, the great effort needed in the data handling procedure and in the data submission procedure becomes the crucial limitation for experimentalists to contribute to a database, thereby impeding the database to deliver its benefit. Moreover, manual copy and paste operations which are commonly used in those procedures increase the chance of making mistakes. Excemplify, a web-based application, proposes a flexible and adaptable template-based solution to solve these problems. Comparing to the normal template based uploading approach, which is supported by some public databases, rather than predefining a format that is potentiall impractical, Excemplify allows users to create their own experiment-specific content templates in different experiment stages and to build corresponding knowledge bases for parsing. Utilizing the embedded knowledge of used templates, Excemplify is able to parse experimental data from the initial setup stage and generate following stages spreadsheets automatically. The proposed solution standardizes the flows of data traveling according to the standard procedures of applying the experiment, cuts down the amount of manual effort and reduces the chance of mistakes caused by manual data handling. In addition, it maintains the context of meta-data from the initial preparation manuscript and improves the data consistency. It interoperates and complements RightField and SEEK as well.


Assessment of food consumption, energy and protein intake in the meals offered in four Spanish nursing homes.
The elderly, and especially those attending nursing homes, are at great risk from certain nutritional deficiencies. The aim of this study was to examine the percentage of energy wasted, energy and protein intake and percentage consumed of meal offered by a group of healthy institutionalized elderly in four nursing homes in Spain. This was a multicentre observational study of a sample of the institutionalized population over the age of 65. Our final sample comprised a total of 62 individuals. Dietary data were collected using double weight method for each meal during 21 days. We calculated the following consumption variables: percentage of food consumed (% food consumed) for each subject in each meal. We also calculated the energy intake (kcal/day), the wasted energy (kcal/day), the protein intake (g protein/ day) and the energy density (kcal/g meal) for each of the meals eaten. To analyse the overall differences we used analysis of variance test (ANOVA). The significance level used was 0.05 (p < 0.05). The largest meals were lunch (781 g/day [728.4, 833.6]) and dinner (653 g/day [612.1, 693.9]). The percentage of total consumption was 81.9% [79.3, 84.6]. The average energy consumption was 1,575.4 kcal/day [1,508.3, 1,642.6]. The percentage of caloric distribution varied depending on the center. The highest percentage of wasted food was found in the main meals. Forty four percent did not consume enough energy to meet the recommended intakes. Protein intake was 63.6 g protein / day [61.2, 66.1]. 12.5% of women and 4.55% of men did not consume the recommended intakes for the elderly. Breakfast and the bedtime snack had the highest energy density with 1.10 [0.9, 1.25] and 1.04 [0.9, 1.08] kcal/g food served respectively [Energy density]. DISCUSION/CONCLUSIONS: The best strategy for increasing the energy intake of the institutionalized elderly without raising the amount of food that is rejected may be to provide higher energy density foods in the same serving sizes.


Maternal drug use and the timing of prenatal care.
This paper explores the role of maternal drug use and the timing of prenatal care. The study data were collected from women delivering live births at eight participating hospitals in the Washington, D.C., Metropolitan Area Drug Study. An estimated 16.9 percent of the women in this sample initiated prenatal care in their third trimester or received no prenatal care. After adjusting for age, race/ethnicity, education, parity, and attitude toward pregnancy, cocaine use was strongly associated with the timing of prenatal care. Using multivariable ordinal logistic regression, the data suggest significant barriers to prenatal care for substance abusers, especially cocaine users. Increasing access to prenatal care continues to be an important public health policy objective, particularly in urban areas where substance abuse is prevalent. Health services research must test strategies that address the timing of prenatal care among drug-dependent, urban women.


Polymerase chain reaction genotyping of Epstein-Barr virus in scraping samples of the tongue lateral border in HIV-1 seropositive patients.
The Epstein-Barr virus (EBV) is the etiological agent of oral hairy leukoplakia (OHL), an oral lesion with important diagnostic and prognostic value in acquired immunodeficiency disease syndrome. The two EBV genotypes, EBV-1 and EBV-2, can be distinguished by divergent gene sequences encoding the EBNA-2, 3A, 3B, and 3C proteins. The purpose of this study was to identify the EBV genotype prevalent in 53 samples of scrapings from the lateral border of the tongue of HIV-1 seropositive patients, with and without OHL, and to correlate the genotypes with presence of clinical or subclinical OHL with the clinic data collected. EBV-1 and EBV-2 were identified through PCR and Nested-PCR based on sequence differences of the EBNA-2 gene. EBV-1 was identified in the 31 samples (15 without OHL, 7 with clinical OHL and 9 with subclinical OHL), EBV-2 in 12 samples (10 without OHL, 1 with clinical and 1 subclinical OHL), and a mixed infection in 10 samples (2 without OHL, 3 with clinical and 5 with subclinical OHL). The presence of EBV-1 was higher in women, but a significant statistical result relating one the EBV genotypes to the development of OHL was not found. We conclude that the oral epithelium in HIV-1 seropositive patients can be infected by EBV-1, EBV-2 or by a mixed viral population.


Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding--a European perspective.
Our aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage. A guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A-E according to the strength of evidence available. Consensus was sought among the committee for each recommendation. A recommendation for use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E) and bleeding following cardiac surgery (grade D). rFVIIa could not be recommended for use: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child-Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child-Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team. There is a rationale for using rFVIIa to treat massive bleeding in certain indications; however, only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.


Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study.
Current indications for therapeutic hypothermia (TH) are restricted to comatose patients with cardiac arrest (CA) due to ventricular fibrillation (VF) and without circulatory shock. Additional studies are needed to evaluate the benefit of this treatment in more heterogeneous groups of patients, including those with non-VF rhythms and/or shock and to identify early predictors of outcome in this setting. Prospective study, from December 2004 to October 2006. 32-bed medico-surgical intensive care unit, university hospital. Comatose patients with out-of-hospital CA. TH to 33 +/- 1 degrees C (external cooling, 24 hrs) was administered to patients resuscitated from CA due to VF and non-VF (including asystole or pulseless electrical activity), independently from the presence of shock. We hypothesized that simple clinical criteria available on hospital admission (initial arrest rhythm, duration of CA, and presence of shock) might help to identify patients who eventually survive and might most benefit from TH. For this purpose, outcome was related to these predefined variables. Seventy-four patients (VF 38, non-VF 36) were included; 46% had circulatory shock. Median duration of CA (time from collapse to return of spontaneous circulation [ROSC]) was 25 mins. Overall survival was 39.2%. However, only 3.1% of patients with time to ROSC > 25 mins survived, as compared to 65.7% with time to ROSC < or = 25 mins. Using a logistic regression analysis, time from collapse to ROSC, but not initial arrest rhythm or presence of shock, independently predicted survival at hospital discharge. Time from collapse to ROSC is strongly associated with outcome following VF and non-VF cardiac arrest treated with therapeutic hypothermia and could therefore be helpful to identify patients who benefit most from active induced cooling.


Gender Differences in Predictors of Physical Activity among Korean College Students Based on the Health Promotion Model.
Aim: Despite the numerous physical and psychological benefits of physical activity (PA), the prevalence of achieving PA recommendations decreases in college students. Therefore, this study was conducted to identify factors influencing PA in male and female college students based on the Health Promotion Model. Methods: A quantitative, cross-sectional research design was used to investigate factors influencing PA among male and female college students. A convenience sample of 264 Korean students was recruited from three colleges. Participants completed measures of physical activity, perceived benefits/barriers to PA, PA self-efficacy, activity-related affect, and peer support. Results: A multiple regression analysis indicated that the factors affecting PA in male college students were PA self-efficacy and subjective economic status, while the factors affecting PA in female students were PA self-efficacy, subjective health status, activity-related affect, and peer support. Conclusions: School health centers or wellness centers need to develop exercise self-efficacy enhancement programs to provide motivation for PA among college students. It might also be necessary to develop a customized PA program that considers gender differences.


Methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern.
Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. In this communication, we analyze methylation data from the Illumina HumanMethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification.


Cellular pharmacology of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine in the human leukemic cell lines K-562 and U-937.
The mechanisms of cytotoxicity, cellular drug uptake, intracellular drug distribution, cellular pharmacokinetics, formation of arabinofuranosylcytosine triphosphate (ara-CTP), and DNA incorporation of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC), a new lipophilic derivative of arabinofuranosylcytosine (ara-C) formulated in small unilamellar liposomes, were determined in vitro in the human leukemic cell lines K-562 and U-937. Furthermore, the induction of erythroid differentiation by NHAC was tested in K-562 cells. The cytotoxicity of NHAC in both cell lines was not influenced by the deoxycytidine (dCyd) concentration or the presence of the nucleoside-transport-blocking agent dipyridamole as demonstrated in coincubations with dCyd and/or dipyridamole, whereas in contrast, the cytotoxicity of ara-C was decreased additively by both drugs. As compared with ara-C, the uptake of NHAC displayed up to 16- and 5-fold increases in K-562 and U-937 cells, respectively, depending on the drug concentration. Studies of the drug distribution and pharmacokinetics of NHAC revealed a depot effect for NHAC in the cell membranes, resulting in half-lives 2.6 and 1.4 times longer than those of ara-C in the two cell lines. The ara-CTP concentrations derived from NHAC were 150- and 75-fold lower at a drug concentration of 1 microM in K-562 and U-937 cells, respectively. The DNA incorporation of the drugs observed after incubation with 2 microM NHAC was 60- and 30-fold lower as compared with that seen at 2 microM ara-C in the two cell lines. Furthermore, NHAC was capable of inducing irreversible erythroid differentiation to a maximum of only 22% of K-562 cells, whereas ara-C induced differentiation at a drug concentration 100-fold lower in 50% of the cells. These results indicate a mechanism of cytotoxicity for NHAC that is independent of the nucleoside transport mechanism and the phosphorylation pathway and suggest that the mechanisms of action of NHAC are significantly different from those of ara-C. Therefore, NHAC might be used for the treatment of ara-C-resistant malignancies.


Corn Silk Tea for Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Corn silk, a traditional Chinese medicine, has been found to exert an antihypertensive effect in clinical practice and trials. However, systematic review of current evidence on this topic was not available. Thus, this study aims to assess safety and efficacy of corn silk tea (CST) in improving clinical outcomes in patients with hypertension. A systematic literature search was conducted through popular electronic databases up to October 2018. Randomized controlled trials (RCTs) comparing CST plus conventional antihypertensive drugs with conventional antihypertensive drugs alone were included. The main outcome was total blood pressure lowering efficacy. The risk of bias assessment according to the Cochrane Handbook was used to evaluate the methodological quality of the included trials. Review Manager 5.3 software was used for data analyses. Five RCTs involving 567 participants were included. Due to the poor quality of methodologies of most trials, limited evidence showed that CST plus antihypertensive drugs might be more effective in lowering blood pressure compared with antihypertensive drugs alone (RR = 1.27; 95% CI: 1.17 to 1.38, P<0.00001; heterogeneity: P = 0.51, I 2 = 0%, fixed-effect model). However, there is no evidence that CST plus conventional antihypertensive drugs has less adverse events than conventional antihypertensive drugs.


Construction of a teaching package on promoting prosocial internet use and preventing antisocial Internet use.
In the construction of the teaching package on the Internet use, two major moral characters, respect and responsibility, form the core theoretical basis. The respect character consists of respect for others and self-respect while the responsibility character contains social, civil, and global responsibility. There are a total of nine units on the Internet use in the junior secondary curriculum. There are two units in Secondary One curriculum: the first unit deals with cheating behavior and privacy issues concerning the Internet, and the second one discusses the effect of excessive use of the Internet on life and study. In Secondary Two curriculum, we discuss the following social phenomena on the Internet with students: online shopping, pornographic materials on internet, and infringement of a copyright. Finally, we have designed four units on the Internet use in Secondary Three curriculum which focuses more on the relationship between the Internet use and our health. We try to answer the question on how we can use the Internet healthily and also the possibility on how it may hurt us. Similar to the second unit in Secondary One curriculum, we have designed three more units on discussing the effects of excessive use of the Internet with students. We would like to alert students that ineffective use of the Internet will hurt us mentally and physically. For illustrative purposes, two units in the Secondary One and Two curriculums are outlined in this paper.


Facile synthesis and electrochemical performances of hollow graphene spheres as anode material for lithium-ion batteries.
The hollow graphene oxide spheres have been successfully fabricated from graphene oxide nanosheets utilizing a water-in-oil emulsion technique, which were prepared from natural flake graphite by oxidation and ultrasonic treatment. The hollow graphene oxide spheres were reduced to hollow graphene spheres at 500°C for 3 h under an atmosphere of Ar(95%)/H2(5%). The first reversible specific capacity of the hollow graphene spheres was as high as 903 mAh g(-1) at a current density of 50 mAh g(-1). Even at a high current density of 500 mAh g(-1), the reversible specific capacity remained at 502 mAh g(-1). After 60 cycles, the reversible capacity was still kept at 652 mAh g(-1) at the current density of 50 mAh g(-1). These results indicate that the prepared hollow graphene spheres possess excellent electrochemical performances for lithium storage. The high rate performance of hollow graphene spheres thanks to the hollow structure, thin and porous shells consisting of graphene sheets. 81.05.ue; 61.48.Gh; 72.80.Vp.


MPIC: Molecular Prognostic Indicators in Cirrhosis Database for Clinical Context-Specific in Silico Prognostic Biomarker Validation.
Prognostic biomarkers are vital in the management of progressive chronic diseases such as liver cirrhosis, affecting 1-2% of the global population and causing over 1 million deaths every year. Despite numerous candidate biomarkers in literature, the costly and lengthy process of validation hampers their clinical translation. Existing omics databases are not suitable for in silico validation due to the ignorance of critical factors, i.e., study design, clinical context of biomarker application, and statistical power. To address the unmet need, we have developed the Molecular Prognostic Indicators in Cirrhosis (MPIC) database as a representative example of an omics database tailored for prognostic biomarker validation. MPIC consists of (i) a molecular and clinical database structured by defined disease context and specific clinical outcome and annotated with employed study design and anticipated statistical power by disease domain experts, (ii) a bioinformatics analysis engine for user-provided gene-signature- or gene-based prognostic prediction, and (iii) a user interface for interactive exploration of relevant clinical cohort/scenario and assessment of significance and reliability of the result for prognostic prediction. MPIC assists cost-effective prognostic biomarker development by facilitating the process of validation, and will transform the care of chronic diseases such as cirrhosis. MPIC is freely available at www.mpic-app.org. The website is implemented in Java, Apache, and MySQL with all major browsers supported.


Burden of Liver Abscess and Survival Risk Score in Thailand: A Population-Based Study.
In Thailand, the burden of liver abscess, a life-threatening infectious disease, has not been thoroughly evaluated. We developed a predictive scoring system to estimate survival of patients with liver abscess using information from the 2008-2013 Nationwide Hospital Admission Data to evaluate the burden of liver abscess in Thailand. All patients with primary diagnosis of pyogenic liver abscess (PLA) and amoebic liver abscess (ALA) were included. Epidemiological data, baseline characteristics, hospital course, and survival were analyzed. Overall, 11,296 admissions comprising 8,423 patients from 844 hospitals across Thailand were eligible for analysis. The mean age was 52 ± 17 years and 66.1% of patients were male. ALA was significantly prevalent in southern and western border regions of Thailand, and PLA occurred nationwide. The highest incidence of liver abscess occurred in the rainy season (June-November, P < 0.01). The median length of hospital stay was 8 days (interquartile range = 4-13 days), and mean direct cost of hospitalization was 846 ± 1,574 USD. The overall inhospital mortality rate was 2.8%. Incidence of ALA decreased over the 5-year study period, whereas PLA incidence increased (P < 0.01). Using multivariable Cox regression methods with stepwise variable selection, we developed a final model with five highly significant baseline parameters associated with increased 60-day mortality: older age, PLA, underlying chronic kidney disease, cirrhosis, and human immunodeficiency virus infection. Range of estimated probability of 60-day survival was 95-16% at cumulative risk score 0-13. This simplified score is practical, and may help clinicians prioritize patients requiring more intensive care.


Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment.
OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.


A Single-center Experience of Esophageal Eosinophilia.
Esophageal eosinophilia occurs in many conditions, including eosinophilic esophagitis (EoE) and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), which have been increasingly recognized in Western countries. There have been only a few reports in Korea. Here, we evaluated the clinical and endoscopic characteristics of patients with esophageal eosinophilia from our experience. Nineteen patients were diagnosed with esophageal eosinophilia based on typical symptoms, endoscopic features, esophageal eosinophilia with ≥15 eosinophils/high power field, and response to medication by PPI. Symptoms, endoscopic and pathological findings were evaluated. Of the 19 patients, 2 patients were diagnosed with EoE, 7 patients were diagnosed with PPI-REE, and 10 patients were undetermined due to loss to follow-up. Among these 19 patients, dysphagia was present in 11, and heartburn, dyspepsia and refluxin 8. Sixteen patients had common endoscopic features, such as longitudinal furrows, concentric rings, strictures, and white plaques; however, 3 patients had normal findings. Nine patients underwent endoscopy at the time of follow-up. Two patients had complete resolution, and 3 had partial resolution. However, 4 patients showed no endoscopic changes. All patients showed symptom improvements. The clinical and endoscopic characteristics of both groups in Korea were undistinguishable. However, after treatment, endoscopic findings were different between the two groups. Large-scale studies are warranted to confirm our findings.


Twitter-Based Analysis of the Dynamics of Collective Attention to Political Parties.
Large-scale data from social media have a significant potential to describe complex phenomena in the real world and to anticipate collective behaviors such as information spreading and social trends. One specific case of study is represented by the collective attention to the action of political parties. Not surprisingly, researchers and stakeholders tried to correlate parties' presence on social media with their performances in elections. Despite the many efforts, results are still inconclusive since this kind of data is often very noisy and significant signals could be covered by (largely unknown) statistical fluctuations. In this paper we consider the number of tweets (tweet volume) of a party as a proxy of collective attention to the party, identify the dynamics of the volume, and show that this quantity has some information on the election outcome. We find that the distribution of the tweet volume for each party follows a log-normal distribution with a positive autocorrelation of the volume over short terms, which indicates the volume has large fluctuations of the log-normal distribution yet with a short-term tendency. Furthermore, by measuring the ratio of two consecutive daily tweet volumes, we find that the evolution of the daily volume of a party can be described by means of a geometric Brownian motion (i.e., the logarithm of the volume moves randomly with a trend). Finally, we determine the optimal period of averaging tweet volume for reducing fluctuations and extracting short-term tendencies. We conclude that the tweet volume is a good indicator of parties' success in the elections when considered over an optimal time window. Our study identifies the statistical nature of collective attention to political issues and sheds light on how to model the dynamics of collective attention in social media.


Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration.
Following myonecrosis, muscle satellite cells proliferate, differentiate and fuse, creating new myofibers. The Runx1 transcription factor is not expressed in naïve developing muscle or in adult muscle tissue. However, it is highly expressed in muscles exposed to myopathic damage yet, the role of Runx1 in muscle regeneration is completely unknown. Our study of Runx1 function in the muscle's response to myonecrosis reveals that this transcription factor is activated and cooperates with the MyoD and AP-1/c-Jun transcription factors to drive the transcription program of muscle regeneration. Mice lacking dystrophin and muscle Runx1 (mdx-/Runx1f/f), exhibit impaired muscle regeneration leading to age-dependent muscle waste, gradual decrease in motor capabilities and a shortened lifespan. Runx1-deficient primary myoblasts are arrested at cell cycle G1 and consequently differentiate. Such premature differentiation disrupts the myoblasts' normal proliferation/differentiation balance, reduces the number and size of regenerating myofibers and impairs muscle regeneration. Our combined Runx1-dependent gene expression, ChIP-seq, ATAC-seq and histone H3K4me1/H3K27ac modification analyses revealed a subset of Runx1-regulated genes that are co-occupied by MyoD and c-Jun in mdx-/Runx1f/f muscle. The data provide unique insights into the transcriptional program driving muscle regeneration and implicate Runx1 as an important participant in the pathology of muscle wasting diseases.


Update on the relationship between magnesium and exercise.
Magnesium is involved in numerous processes that affect muscle function including oxygen uptake, energy production and electrolyte balance. Thus, the relationship between magnesium status and exercise has received significant research attention. This research has shown that exercise induces a redistribution of magnesium in the body to accommodate metabolic needs. There is evidence that marginal magnesium deficiency impairs exercise performance and amplifies the negative consequences of strenuous exercise (e.g., oxidative stress). Strenuous exercise apparently increases urinary and sweat losses that may increase magnesium requirements by 10-20%. Based on dietary surveys and recent human experiments, a magnesium intake less than 260 mg/day for male and 220 mg/day for female athletes may result in a magnesium-deficient status. Recent surveys also indicate that a significant number of individuals routinely have magnesium intakes that may result in a deficient status. Athletes participating in sports requiring weight control (e.g., wrestling, gymnastics) are apparently especially vulnerable to an inadequate magnesium status. Magnesium supplementation or increased dietary intake of magnesium will have beneficial effects on exercise performance in magnesium-deficient individuals. Magnesium supplementation of physically active individuals with adequate magnesium status has not been shown to enhance physical performance. An activity-linked RNI or RDA based on long-term balance data from well-controlled human experiments should be determined so that physically active individuals can ascertain whether they have a magnesium intake that may affect their performance or enhance their risk to adverse health consequences (e.g., immunosuppression, oxidative damage, arrhythmias).


Temperature-dependent optoelectronic properties of quasi-2D colloidal cadmium selenide nanoplatelets.
Colloidal cadmium selenide (CdSe) nanoplatelets (NPLs) are a recently developed class of efficient luminescent nanomaterials suitable for optoelectronic device applications. A change in temperature greatly affects their electronic bandstructure and luminescence properties. It is important to understand how and why the characteristics of NPLs are influenced, particularly at elevated temperatures, where both reversible and irreversible quenching processes come into the picture. Here we present a study of the effect of elevated temperatures on the characteristics of colloidal CdSe NPLs. We used an effective-mass envelope function theory based 8-band k·p model and density-matrix theory considering exciton-phonon interaction. We observed the photoluminescence (PL) spectra at various temperatures for their photon emission energy, PL linewidth and intensity by considering the exciton-phonon interaction with both acoustic and optical phonons using Bose-Einstein statistical factors. With a rise in temperature we observed a fall in the transition energy (emission redshift), matrix element, Fermi factor and quasi Fermi separation, with a reduction in intraband state gaps and increased interband coupling. Also, there was a fall in the PL intensity, along with spectral broadening due to an intraband scattering effect. The predicted transition energy values and simulated PL spectra at varying temperatures exhibit appreciable consistency with the experimental results. Our findings have important implications for the application of NPLs in optoelectronic devices, such as NPL lasers and LEDs, operating much above room temperature.


Quantification of population structure using correlated SNPs by shrinkage principal components.
Association studies using unrelated individuals have become the most popular design for mapping complex traits. One of the major challenges of association mapping is avoiding spurious association due to population stratification. Principal component analysis (PCA) on genome-wide marker genotypes is one of the most popular population stratification control methods. It implicitly assumes that the markers are in linkage equilibrium, a condition that is rarely satisfied and that we plan to relax. We carefully examined the impact of linkage disequilibrium (LD) on PCA, and proposed a simple modification of the standard PCA to automatically adjust for the correlations among markers. We demonstrated that LD patterns in genome-wide association datasets can distort the techniques for stratification control, showing 'subpopulations' reflecting localized LD phenomena rather than plausible population structure. We showed that the proposed method effectively removes the artifactual effect of LD patterns, and successfully recovers underlying population structure that is not apparent from standard PCA. PCA is highly influenced by sets of SNPs with high LD, obscuring the true population substructure. Our shrinkage PCA applies to all available markers, regardless of the LD patterns. The proposed method is easier to implement than most existing LD adjusted PCA methods.


Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review.
To determine (1) whether platelet-rich plasma (PRP) injection significantly improves validated patient-reported outcomes in patients with symptomatic knee osteoarthritis (OA) at 6 and 12 months postinjection, (2) differences in outcomes between PRP and corticosteroid injections or viscosupplementation or placebo injections at 6 and 12 months postinjection, and (3) similarities and differences in outcomes based on the PRP formulations used in the analyzed studies. PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and Sport Discus were searched for English-language, level I evidence, human in vivo studies on the treatment of symptomatic knee OA with intra-articular PRP compared with other options, with a minimum of 6 months of follow-up. A quality assessment of all articles was performed using the Modified Coleman Methodology Score (average, 83.3/100), and outcomes were analyzed using 2-proportion z-tests. Six articles (739 patients, 817 knees, 39% males, mean age of 59.9 years, with 38 weeks average follow-up) were analyzed. All studies met minimal clinical important difference criteria and showed significant improvements in statistical and clinical outcomes, including pain, physical function, and stiffness, with PRP. All but one study showed significant differences in clinical outcomes between PRP and hyaluronic acid (HA) or PRP and placebo in pain and function. Average pretreatment Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 52.36 and 52.05 for the PRP and HA groups, respectively (P = .420). Mean post-treatment WOMAC scores for PRP were significantly better than for HA at 3 to 6 months (28.5 and 43.4, respectively; P = .0008) and at 6 to 12 months (22.8 and 38.1, respectively; P = .0062). None of the included studies used corticosteroids. In patients with symptomatic knee OA, PRP injection results in significant clinical improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months postinjection. There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP or PRP versus steroids in this study. Level I, systematic review of Level I studies.


Renal function outcomes after laparoscopic renal cryoablation.
Laparoscopic cryoablation (LCA) has emerged as an alternative to conventional surgery for the management of a T(1) renal mass; however, only few data are available on its functional outcomes. We assessed renal function changes after LCA in patients with normal renal function (NRF) and preexisting chronic renal insufficiency (CRI). Data of consecutive patients who were undergoing LCA between 2000 and 2008 at Duke University Medical Center were analyzed. Renal function parameters were obtained preoperatively, at discharge, and at 6, 12, and 24 months postoperatively. Serum creatinine (sCr) levels and estimated glomerular filtration rates (eGFR) were compared over a 2-year follow-up. Of 67 patients, 22 (33%) had CRI at baseline. These patients were older, had larger tumors (2.5 vs 2.0 cm, P=0.039), and a higher incidence of multiple lesions (22.7% vs 4.4%, P=0.034). Compared with baseline, sCr was significantly increased and eGFR declined at discharge, 6, 12, and 24 months in both NRF and CRI groups. Median sCr increase was 0.1 mg/mL, eGFR declined by 4.2 mg/mL/1.73 m(2) in the CRI cohort and up to 8.8 mg/mL/1.73m(2) in NRF patients (all P<0.05) during the follow-up. Compared with baseline, however, no significant changes were noted in the distribution of CRI categories at any time (all P>0.05). A minimal decline in renal function can be appreciated in patients undergoing LCA at midterm follow-up. This decline is no higher in CRI than in NRF patients. LCA offers excellent renal function outcomes at 2 years follow-up. Specifically, in patients with CRI, LCA offers excellent preservation of renal function.


Analysis of the Relationship between Scintillation Parameters, Multipath and ROTI.
Global Navigation Satellite System (GNSS) operation can be affected by several environmental factors, of which ionospheric scintillation is one of the most significant. Scintillation is usually characterized by two indices, namely the amplitude scintillation index (S4) and phase scintillation index (σφ). However, these two indices can only be generated by specialized GNSS receivers, which are not widely available all around the world. To popularize the study of scintillation, this article proposes to use more accessible parameters, namely multipath (MP) and rate of change of total electron content index (ROTI), to characterize scintillation. Using GPS data obtained on six days in total from three stations, namely PRU2 and SAO0P located in Sao Paulo, Brazil and SNA0P located in Antarctica, respectively, both the time series plots and 2D maps were generated to investigate the relationship of scintillation indices (S4 and σφ) with MP and ROTI. To prevent the effect of the real multipath error, a 30-degree satellite elevation mask is applied to all the data. As the scintillation indices S4 and σφ have a sampling interval of 1 min, MP and ROTI are calculated with the same sampling interval for a more direct comparison. The results show that the structural similarity (SSIM) and correlation coefficient (CC) between parameters was greater than 0.7 for 70% of outputs. In addition, the variogram and cross-variogram are applied to investigate the spatial structure of the MP, ROTI, S4 and σφ in order to support the results of SSIM and CC. With outputs in three forms, promising spatial and temporal relationships between parameters was observed.


Crossover from localized to itinerant states in hydrocarbon Mott insulators.
Crossover from an itinerant state to an isolated electronic state in electron-doped polycyclic aromatic hydrocarbon (PAH) was studied for the two smallest zigzag-type molecules of naphthalene (NN) and anthracene (AN) by focusing on their 1 : 1 stoichiometry, A1(NN) and A1(AN), with alkali metals (A = K and Rb). The competition between on-site Coulombic repulsion energy (U) and bandwidth (W) was argued in terms of their magnetic and electrical properties upon lattice expansion, when A varies from K, with a smaller ionic radius, to Rb, with a larger ionic radius. The temperature-dependence of magnetic susceptibility shows a pronounced hump associated with antiferromagnetic (AFM) interactions for Rb1(NN), being similar to those of K1(NN) and K1(AN) in the earlier report. On the other hand, Rb1(AN) intriguingly exhibits paramagnetic susceptibility, observed in a nearly localized electron system, being apart from an highly correlated Mott insulating state. Crystal structural analyses of the X-ray diffraction profiles show a small difference in lattice parameters of the ab plane among K1(NN), K1(AN), and Rb1(NN), whereas Rb1(AN) exhibits a significantly larger value than those of the others, being indicative of greatly modified interaction energies. The different magnetic properties observed in Rb1(AN) are interpreted from its modified intermolecular distance. The possibility of an emergent metallic state of K1(AN) under high pressure has also been described, referring to electrical transport measured under high pressure.


Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.
Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.


On the predictability of the orientation of protein domains joined by a spanning alpha-helical linker.
Connecting proteins together in prescribed geometric arrangements is an important element in new areas of biomolecular design. In this study, we characterize the degree of three-dimensional orientational control that can be achieved when two protein domains that have alpha-helical termini are joined using an alpha-helical linker. A fusion between naturally oligomeric protein domains was designed in this fashion with the intent of creating a self-assembling 12-subunit tetrahedral protein cage. While the designed fusion protein failed to assemble into a tetrahedral cage in high yield, a series of crystal structures showed that the two fused components were indeed bridged by an intact alpha helix, although the fusion protein was distorted from the intended ideal configuration by bending of the helix, ranging from 7 to 35°. That range of deviation in orientation creates challenges for designing large, perfectly symmetric protein assemblies, although it should offer useful outcomes for other less geometrically demanding applications in synthetic biology.


Ontogeny of NHE8 in the rat proximal tubule.
Proximal tubule bicarbonate reabsorption is primarily mediated via the Na(+)/H(+) exchanger, identified as NHE3 in adults. Previous studies have demonstrated a maturational increase in rat proximal tubule NHE3 expression, with a paucity of NHE3 expression in neonates, despite significant Na(+)-dependent proton secretion. Recently, a novel Na(+)/H(+) antiporter (NHE8) was identified and found to be expressed on the apical membrane of the proximal tubule. To determine whether NHE8 may be the antiporter responsible for proton secretion in neonates, the present study characterized the developmental expression of NHE8 in rat proximal tubules. RNA blots and real-time RT-PCR demonstrated no developmental difference in the mRNA of renal NHE8. Immunoblots, however, demonstrated peak protein abundance of NHE8 in brush border membrane vesicles of 7- and 14-day-old compared with adult rats. In contrast, the level of NHE8 expression in total cortical membrane protein was higher in adults than in neonates. Immunohistochemistry confirmed the presence of NHE8 on the apical membrane of the proximal tubules of neonatal and adult rats. These data demonstrate that NHE8 does undergo maturational changes on the apical membrane of the rat proximal tubule and may account for the Na(+)-dependent proton flux in neonatal proximal tubules.


Quantitative analysis of the surgical exposure and surgical freedom between transcranial and transorbital endoscopic anterior petrosectomies to the posterior fossa.
This study proposes a variation of the transorbital endoscopic approach (TOEA) that uses the lateral orbit as the primary surgical corridor, in a minimally invasive fashion, for the posterior fossa (PF) access. The versatility of this technique was quantitatively analyzed in comparison with the anterior transpetrosal approach (ATPA), which is commonly used for managing lesions in the PF. Anatomical dissections were carried out in 5 latex-injected human cadaveric heads (10 sides). During dissection, the PF was first accessed by TOEAs through the anterior petrosectomy, both with and without lateral orbital rim osteotomies (herein referred as the lateral transorbital approach [LTOA] and the lateral orbital wall approach [LOWA], respectively). ATPAs were performed following the orbital approaches. The stereotactic measurements of the area of exposure, surgical freedom, and angles of attack to 5 anatomical targets were obtained for statistical comparison by the neuronavigator. The LTOA provided the smallest area of exposure (1.51 ± 0.5 cm2, p = 0.07), while areas of exposure were similar between LOWA and ATPA (1.99 ± 0.7 cm2 and 2.01 ± 1.0 cm2, respectively; p = 0.99). ATPA had the largest surgical freedom, whereas that of LTOA was the most restricted. Similarly, for all targets, the vertical and horizontal angles of attack achieved with ATPA were significantly broader than those achieved with LTOA. However, in LOWA, the removal of the lateral orbital rim allowed a broader range of movement in the horizontal plane, thus granting a similar horizontal angle for 3 of the 5 targets in comparison with ATPA. The TOEAs using the lateral orbital corridor for PF access are feasible techniques that may provide a comparable surgical exposure to the ATPA. Furthermore, the removal of the orbital rim showed an additional benefit in an enhancement of the surgical maneuverability in the PF.


Size and isotope effects of helium clusters and droplets: identification of surface and bulk-volume excitations.
We report a comprehensive investigation of the electronically excited states of helium clusters and droplets of sizes ranging from a few to several 10(7) atoms using time-resolved fluorescence excitation spectroscopy and quantum chemical ab initio calculations. We employ various approaches for our analysis considering the lifetime-dependence of the fluorescence intensity, spectral shifts, intensity scaling with cluster size, isotopic dependence, and density-dependence of the calculated electron wave function radii. A unique feature of helium clusters and droplets is their radially varying particle density. Our results show that short-lived fluorescence is sensitive to regions of increased density and probes excitations located in the bulk volume, whereas long-lived fluorescence is sensitive to regions of reduced density such as for small clusters or for the surface of large droplets. Spectra of (3)He droplets serve as a reference for low density, but are free from contributions of small clusters. This allows us to distinguish regions of reduced density as these can be due to both surface states or small clusters. Our analysis reveals a picture where spectral features are related to regions of different density due to isotopic composition, cluster size, and surface or bulk volume location of the excitations. The 2s and 2p related excitations appear as blue-shifted wings for small clusters or for excited atoms within the surface layer, whereas in the bulk-volume of large droplets, they appear as distinct bands with large intensities, dominating the entire spectrum. Excitations at energies higher than 23 eV are unambiguously assigned to regions of low and medium density location within the deeper parts of the surface layer but show no relation to the bulk volume. Our findings support the idea that in liquid helium high-lying states and, in particular, Rydberg states are quenched in favor of the 2s and 2p excitations.


Exposing the impact of intensive advice services on health: A realist evaluation.
Attention has turned to welfare advice as a potential health and social care intervention. However, establishing direct evidence of health impact has proven difficult. This is compounded by the need to understand both the facilitative contexts and mechanisms through which this impact occurs. This study investigated if, how and in which circumstances an intensive advice service had an impact on stress and well-being (as precursors to health impacts), for clients attending a branch of Citizens Advice, located in the North East of England. A mixed methods realist evaluation of three intensive advice services offered by Citizens Advice (CA) was operationalised in five phases: (a) Building programme theories, (b) refining programme theories, (c) Development of a data recording tool, (d) Testing programme theories with empirical data, (e) Impact interviews. This paper focuses on phase 4. The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) and Perceived Stress Scale (PSS) were completed by 191 clients, with a 91% follow-up rate (data collected: February 2016 to March 2017). Twenty-two CA clients participated in interviews (data collected: October 2015 to November 2016). The PSS indicated a significant decrease in stress from initial consultation to approximately 4-6 weeks post advice from 31.4 to 10.3 (p < 0.001) and the WEMWBS indicated a significant increase in client well-being from a mean of 26.9 to 46.5 (p < 0.001). Nine refined programme theories are presented which combine the qualitative and quantitative analysis; they are underpinned by three abstract theories: Capabilities model, The Decision to Trust Model, and Third Space. An explanatory framework is presented covering the micro, meso, and macro levels of CA. Use of a stress and well-being lens has allowed insight into the precursors of health in those receiving intensive advice. Using these measures whilst explaining contextual and mechanistic properties, begins to build a complex and real picture of how advice services impact on health.


Active and adaptive case finding to estimate therapeutic program coverage for severe acute malnutrition: a capture-recapture study.
Coverage is an important indicator to assess both the performance and effectiveness of public health programs. Recommended methods for coverage estimation for the treatment of severe acute malnutrition (SAM) can involve active and adaptive case finding (AACF), an informant-driven sampling procedure, for the identification of cases. However, as this procedure can yield a non-representative sample, exhaustive or near exhaustive case identification is needed for valid coverage estimation with AACF. Important uncertainty remains as to whether an adequate level of exhaustivity for valid coverage estimation can be ensured by AACF. We assessed the sensitivity of AACF and a census method using a capture-recapture design in northwestern Nigeria. Program coverage was estimated for each case finding procedure. The sensitivity of AACF was 69.5% (95% CI: 59.8, 79.2) and 91.9% (95% CI: 85.1, 98.8) with census case finding. Program coverage was estimated to be 40.3% (95% CI 28.6, 52.0) using AACF, compared to 34.9% (95% CI 24.7, 45.2) using the census. Depending on the distribution of coverage among missed cases, AACF sensitivity of at least ≥70% was generally required for coverage estimation to remain within ±10% of the census estimate. Given the impact incomplete case finding and low sensitivity can have on coverage estimation in potentially non-representative samples, adequate attention and resources should be committed to ensure exhaustive or near exhaustive case finding. ClinicalTrials.gov ID NCT03140904. Registered on May 3, 2017.


Nucleoid condensation in Escherichia coli that express a chlamydial histone homolog.
Chlamydial cell types are adapted for either extracellular survival or intracellular growth. In the transcriptionally inert elementary bodies, the chromosome is densely compacted; in metabolically active reticulate bodies, the chromatin is loosely organized. Condensation of the chlamydial nucleoid occurs concomitant with expression of proteins homologous to eukaryotic histone H1. When the Chlamydia trachomatis 18-kilodalton histone homolog Hc1 is expressed in Escherichia coli, a condensed nucleoid structure similar to that of chlamydiae is observed with both light and electron microscopy. These results support a role for Hc1 in condensation of the chlamydial nucleoid.


A case of surgery for kyphosis of the thoracolumbar spine in an elderly patient with dysphagia.
Here we report a case of surgery for kyphosis of the thoracolumbar spine in an elderly patient, in whom surgery was performed because the patient had developed intractable digestive symptoms. The case was that of a 76-year-old female with complaints of back pain and dysphagia. When videofluoroscopic examination (VF) of swallowing was performed in the cardia of the stomach, images that indicated stagnation and the reflux of food were observed. It was easier for the patient to swallow food in the extension position. We performed corrective fusion of the posterior spine. After the surgery, the kyphosis angle was improved to 27°, the patient's back pain was alleviated, and it became easier for the patient to swallow food. VF also showed that the patient's difficulties with the passage of food had improved. We believe that surgery is a good treatment option for cases of kyphosis with digestive symptoms and deteriorating activities of daily living (ADL), even in the absence of pain and paralysis. VF is also useful for performing evaluations before and after surgery.


Antimicrobial resistance in gram-negative hospital isolates: results of the Turkish HITIT-2 Surveillance Study of 2007.
Resistance rates to amikacin, ciprofloxacin, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam in Escherichia coli (n= 438), Klebsiella pneumoniae (n= 444), Pseudomonas aeruginosa (n= 210) and Acinetobacter baumanni (n=200) were determined with e-test in a multicenter surveillance study (Hitit-2) in 2007. ESBL production in Escherichia coli and K. pneumoniae was investigated following the CLSI guidelines. Overall 42.0% of E.coli and 41.4% of K. pneumoniae were ESBL producers. In E. coli , resistance to imipenem was not observed, resistance to ciprofloxacin and amikacin was 58.0% and 5.5% respectively. In K. pneumoniae resistance to imipenem, ciprofloxacin and amikacin was 3.1%, 17.8% 12.4% respectively. In P. aeruginosa the lowest rate of resistance was observed with piperacillin/tazobactam (18.1%). A. baumanni isolates were highly resistant to all the antimicrobial agents, the lowest level of resistance was observed against cefoperazone/sulbactam (52.0%) followed by imipenem (55.5%). this study showed that resistance rates to antimicrobials are high in nosocomial isolates and show variations among the centers.


[Extension of life: the apotheosis of the molecular biomedical sciences?].
Evolutionary biologists have shown that many of the adverse effects associated with the ageing process are the (by)products of certain genes: the manifestation of the negative effects of these genes only late in life has effectively constrained their elimination from the germ line by natural selection. In addition, during evolution genes have evolved that govern mechanisms for the protection of the body against exogenous and endogenous insults. These two types of genes, in interaction both with themselves and with the environment specify the maximum life span of a species. New scientific developments, especially in molecular biology, allow the careful analysis of the genetic information and its manipulation. On the basis of these developments more insight will be obtained in the causes of ageing and it will be possible to design new therapies for many of the adverse effects associated with ageing. In the long term it may be possible to remove the basic causes of ageing by genetic manipulation. The mission of the biomedical sciences may then be considered as completed.


PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer.
Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3(+) T cells and programmed death-1 (PD-1)(+) T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1(+) T cells and the levels of PD-1(+) cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade.


Learning about patient safety: organizational context and culture in the education of health care professionals.
This study investigated the formal and informal ways pre-registration students from medicine, nursing, physiotherapy and pharmacy learn about keeping patients safe. This paper gives an overview of the study and explores findings in relation to organizational context and culture. The study employed a phased design using multiple qualitative methods. The overall approach drew on 'illuminative evaluation'. Ethical approval was obtained. Phase 1 employed a convenience sample of 13 pre-registration courses across the UK. Curriculum documents were gathered, and course directors interviewed. Phase 2 used eight case studies, two for each professional group, to develop an in-depth investigation of learning across university and practice by students and newly-qualified practitioners in relation to patient safety, and to examine the organizational culture that students and newly-qualified staff are exposed to. Analysis was iterative and ongoing throughout the study, using frameworks agreed by all researchers. Patient safety was felt to have become a higher priority for the health care system in recent years. Incident reporting was a key feature of the patient safety agenda within the organizations examined. Staff were often unclear or too busy to report. On the whole, students were not engaged and may not be aware of incident reporting schemes. They may not have access to existing systems in their organization. Most did not access employers' induction programmes. Some training sessions occasionally included students but this did not appear to be routine. Action is needed to develop an efficient interface between employers and education providers to develop up-to-date curricula for patient safety.


Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity.
Vaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza A strains, such a vaccine may protect against all human influenza A strains, which would represent a major advantage over current vaccine strategies. The present study demonstrates that protection is mediated exclusively by Abs, a very important feature of a successful preventive vaccine. However, these Abs neither bind efficiently to the free virus nor neutralize virus infection, but bind to M2 protein expressed on the surface of virus-infected cells. The presence of NK cells is important for protection, whereas complement is not, supposing that protection is mediated via Ab-dependent, cell-mediated cytotoxicity. The absence of neutralizing Abs results in much weaker protection than that achieved by vaccination with UV-inactivated influenza virus. Specifically, whereas neutralizing Abs completely eliminate signs of disease even at high viral challenge doses, M2-specific Abs cannot prevent infection, but merely reduce disease at low challenge doses. M2-specific Abs fail to protect from high challenge doses, as vaccinated mice undergo lethal infection under these conditions. In conclusion, protection mediated by M2-hepatitis B core vaccine would be insufficient during the yearly epidemics, for which full protection is desirable, and overall is clearly inferior to protection achieved by immunization with classical inactivated viral preparations.


The Eukaryotic Promoter Database EPD: the impact of in silico primer extension.
The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of eukaryotic POL II promoters, experimentally defined by a transcription start site (TSS). There may be multiple promoter entries for a single gene. The underlying experimental evidence comes from journal articles and, starting from release 73, from 5' ESTs of full-length cDNA clones used for so-called in silico primer extension. Access to promoter sequences is provided by pointers to TSS positions in nucleotide sequence entries. The annotation part of an EPD entry includes a description of the type and source of the initiation site mapping data, links to other biological databases and bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. Web-based interfaces have been developed that enable the user to view EPD entries in different formats, to select and extract promoter sequences according to a variety of criteria and to navigate to related databases exploiting different cross-references. Tools for analysing sequence motifs around TSSs defined in EPD are provided by the signal search analysis server. EPD can be accessed at http://www.epd. isb-sib.ch.


Reduction-dependent siderophore assimilation in a model pennate diatom.
Iron uptake by diatoms is a biochemical process with global biogeochemical implications. In large regions of the surface ocean diatoms are both responsible for the majority of primary production and frequently experiencing iron limitation of growth. The strategies used by these phytoplankton to extract iron from seawater constrain carbon flux into higher trophic levels and sequestration into sediments. In this study we use reverse genetic techniques to target putative iron-acquisition genes in the model pennate diatom Phaeodactylum tricornutum We describe components of a reduction-dependent siderophore acquisition pathway that relies on a bacterial-derived receptor protein and provides a viable alternative to inorganic iron uptake under certain conditions. This form of iron uptake entails a close association between diatoms and siderophore-producing organisms during low-iron conditions. Homologs of these proteins are found distributed across diatom lineages, suggesting the significance of siderophore utilization by diatoms in the marine environment. Evaluation of specific proteins enables us to confirm independent iron-acquisition pathways in diatoms and characterize their preferred substrates. These findings refine our mechanistic understanding of the multiple iron-uptake systems used by diatoms and help us better predict the influence of iron speciation on taxa-specific iron bioavailability.


The Health Initiative Program for Kids (HIP Kids): effects of a 1-year multidisciplinary lifestyle intervention on adiposity and quality of life in obese children and adolescents--a longitudinal pilot intervention study.
Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents. Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted of fifteen 90-minute educational sessions led by a dietitian, exercise specialist, and social worker. Anthropometric measures, body composition, and QoL (Pediatric Quality of Life Inventory 4.0), were assessed at baseline, 3 months, and 12 months. Laboratory values were measured at baseline and 12 months. The primary outcome measures were change in BMI and BMI z-score, secondary outcome measures included change in QoL and body composition. A paired sample t-test was used to assess within-group differences and 95% confidence intervals were reported for the mean differences. 42 obese children and adolescents (21 girls) completed the 1-year intervention (mean age 12.8 ± 3.14 years). Mean baseline BMI was 31.96 ± 5.94 kg/m(2) and BMI z-score was +2.19 ± 0.34. Baseline QoL (self-assessments and parental assessments) was impaired: mean baseline scores were 74.5 ± 16.5 and 63.7 ± 19.4 for physical functioning and 69.0 ± 14.9 and 64.0 ± 18.3 for emotional functioning, respectively. At 12 months, BMI z-score had decreased (-0.07 ± 0.11, 95% CI: -0.11 to -0.04). BMI (0.80 ± 1.57 kg/m(2), 95% CI 0.31 to 1.29) and fat-free mass (4.02 ± 6.27 kg, 95% CI 1.90 to 6.14) increased, but % body fat and waist circumference did not. Both the parent-reported physical (11.3 ± 19.2, 95% CI 4.7 to 17.9) and emotional (7.7 ± 15.7, 95% CI 2.3 to 13.0) functioning QoL scores and the children's self-reported physical (5.3 ± 17.1, 95% CI 0.5 to 11.1) and emotional (7.9 ± 14.3, 95% CI 3.2 to 12.7) functioning scores significantly improved. Following a 1-year intervention, the participants' BMI z-scores and QoL improved, while other adiposity-related measures of body composition remained unchanged. UMIN Clinical Trials Registry UMIN000015622 .


H2S Stability of Metal-Organic Frameworks: A Computational Assessment.
The H2S stability of a range of metal-organic frameworks (MOFs) was systematically assessed by first-principles calculations. The most likely degradation mechanism was first determined and we identified the rate constant of the degradation reaction as a reliable descriptor for characterizing the H2S stability of MOFs. A qualitative H2S stability ranking was thus established for the list of investigated materials. Structure-stability relationships were further envisaged considering several variables including the nature of the linkers and their grafted functional groups, the pore size, the nature of metal sites, and the presence/nature of coordinatively unsaturated sites. This knowledge enabled the anticipation of the H2S stability of one prototypical MOF, e.g., MIL-91(Ti), which has been previously proposed as a good candidate for CO2 capture. This computational strategy enables an accurate and easy handling assessment of the H2S stability of MOFs and offers a solid alternative to experimental characterizations that require the manipulation of a highly toxic and corrosive molecule.


Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin.
Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) and lung fibroblast (HFL-1) cells, in vitro, showed Hsp10 in the nucleus, before and after CSE exposure; (iii) CSE stimulation did not increase the levels of Hsp10 but did elicit qualitative changes as indicated by molecular weight and isoelectric point shifts; and (iv) Hsp10 nuclear levels increased after CSE stimulation in HFL-1, indicating cytosol to nucleus migration, and although Hsp10 did not bind DNA, it bound a DNA-associated protein.


Human-specific changes of genome structure detected by genomic triangulation.
Knowledge of the rhesus macaque genome sequence enables reconstruction of the ancestral state of the human genome before the divergence of chimpanzees. However, the draft quality of nonhuman primate genome assemblies challenges the ability of current methods to detect insertions, deletions, and copy-number variations between humans, chimpanzees, and rhesus macaques and hinders the identification of evolutionary changes between these species. Because of the abundance of segmental duplications, genome comparisons require the integration of genomic assemblies and data from large-insert clones, linkage maps, and radiation hybrid maps. With genomic triangulation, an integrative method that reconstructs ancestral states and the structural evolution of genomes, we identified 130 human-specific breakpoints in genome structure due to rearrangements at an intermediate scale (10 kilobases to 4 megabases), including 64 insertions affecting 58 genes. Comparison with a human structural polymorphism database indicates that many of the rearrangements are polymorphic.


QEEG changes during switch from depression to hypomania/mania: a case report.
QEEG cordance and low-resolution electromagnetic tomography (LORETA) are relatively new applications of QEEG. Four small-scale studies have shown that decreases of QEEG prefrontal theta cordance after the first week on new antidepressants predict clinical response to treatment in patients with unipolar depression. We calculated prefrontal theta cordance and changes in 3D distribution of brain electrical activity using LORETA in the case of a 54-year old man experiencing his third depressive episode. We did not detect a decrease of prefrontal theta cordance after one week of new treatment and the patient did not respond to this therapy after four weeks. However, we observed a decrease of prefrontal theta cordance after the first week of clomipramine therapy. Manic symptoms emerged after two weeks of clomipramine treatment. A decrease of prefrontal theta cordance preceded the clomipramine induced switch to hypomania during the next episode of depression also. LORETA before and during clomipramine therapies detected a significant increase of theta in the right postcentralis gyrus in the parietal lobe, and a borderline increase of alfa2 in the right middle frontal gyrus. In a patient with bipolar spectrum disorder we found that a treefold change in theta prefrontal cordance preceded mood changes in a similar way as in patients with unipolar depression. We speculate that the changes detected by LORETA can attributed to the anticholinergic activity of clomipramine and the specific effects of a mood switch. Our data suggest that the new applications of QEEG can be sensitive to mood changes and have potential in bipolar disorder research.


An analysis of the sequence variability of meningococcal fHbp, NadA and NHBA over a 50-year period in the Netherlands.
Studies of meningococcal evolution and genetic population structure, including the long-term stability of non-random associations between variants of surface proteins, are essential for vaccine development. We analyzed the sequence variability of factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisseria adhesin A (NadA), three major antigens in the multicomponent meningococcal serogroup B vaccine 4CMenB. A panel of invasive isolates collected in the Netherlands over a period of 50 years was used. To our knowledge, this strain collection covers the longest time period of any collection available worldwide. Long-term persistence of several antigen sub/variants and of non-overlapping antigen sub/variant combinations was observed. Our data suggest that certain antigen sub/variants including those used in 4CMenB are conserved over time and promoted by selection.


Targets of complement-fixing antibodies in protective immunity against malaria in children.
Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.


Physiologically low oxygen concentrations in fetal skin regulate hypoxia-inducible factor 1 and transforming growth factor-beta3.
In the first-trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar-limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in the sheep model in vivo and performed studies on the potential relevance of HIF-1alpha during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF-1alpha could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF-1alpha was expressed in fibroblasts and was markedly up-regulated at the wound edge. In scarring fetal wounds at GD120, HIF-1alpha was predominantly expressed in inflammatory cells. Expression of transforming growth factor beta3 (TGF-beta3), a potent antiscarring cytokine, overlapped with HIF-1a expression at GD100. HIF-1alpha-deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF-beta3, but not proscarring TGF-beta1, manifests hypoxia- and HIF-1alpha-dependent regulation. In conclusion, HIF-1alpha-dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.


Perceptions of parental caring predict health status in midlife: a 35-year follow-up of the Harvard Mastery of Stress Study.
This study examined how the perception of parental caring, obtained from undergraduates, relates to subsequent health over the ensuing 35 years. In the early 1950s, initial ratings of parental caring were obtained from a sample of healthy, Harvard undergraduate men who participated in the Harvard Mastery of Stress Study. In a 35 year prospective, follow-up investigation, detailed medical and psychological histories and medical records were obtained. Subjects identified in midlife as suffering from illnesses such as coronary artery disease, hypertension, duodenal ulcer, and alcoholism, gave their parents significantly lower ratings (p < .00003) on perceived parental caring items (loving, just, fair, hardworking, clever, strong) while in college. This effect was independent of subject's age, family history of illness, smoking behavior, the death and/or divorce of parents, and marital history of subjects. Furthermore, 87% of subjects who rated both their mothers and fathers low in parental caring had diagnosed diseases in midlife, whereas only 25% of subjects who rated both their mothers and fathers high in parental caring had diagnosed diseases in midlife. Since parents are usually the most meaningful source of social support for much of early life, the perception of parental caring, and parental loving itself, may have important regulatory and predictive effects on biological and psychological health and illness.


Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.
The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom. This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d). Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days. We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies. This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.


Quantitative imaging of lipid droplets in single cells.
The combination of next generation sequencing (NGS) and automated liquid handling platforms has led to a revolution in single-cell genomic studies. However, many molecules that are critical to understanding the functional roles of cells in a complex tissue or organs, are not directly encoded in the genome, and therefore cannot be profiled with NGS. Lipids, for example, play a critical role in many metabolic processes but cannot be detected by sequencing. Recent developments in quantitative imaging, particularly coherent Raman scattering (CRS) techniques, have produced a suite of tools for studying lipid content in single cells. This article reviews CRS imaging and computational image processing techniques for non-destructive profiling of dynamic changes in lipid composition and spatial distribution at the single-cell level. As quantitative CRS imaging progresses synergistically with microfluidic and microscopic platforms for single-cell genomic analysis, we anticipate that these techniques will bring researchers closer towards combined lipidomic and genomic analysis.


Space-based constraints on spatial and temporal patterns of NO(x) emissions in California, 2005-2008.
We describe ground and space-based measurements of spatial and temporal variation of NO(2) in four California metropolitan regions. The measurements of weekly cycles and trends over the years 2005-2008 observed both from the surface and from space are nearly identical to each other. Observed decreases in Los Angeles and the surrounding cities are 46% on weekends and 9%/year from 2005-2008. Similar decreases are observed in the San Francisco Bay area and in Sacramento. In the San Joaquin Valley cities of Fresno and Bakersfield weekend decreases are much smaller, only 27%, and the decreasing trend is only 4%/year. We describe evidence that the satellite observations provide a uniquely complete view of changes in spatial patterns over time. For example, we observe variations in the spatial pattern of weekday-weekend concentrations in the Los Angeles basin with much steeper weekend decreases at the eastern edge of the basin. We also observe that the spatial extent of high NO(2) in the San Joaquin Valley has not receded as much as it has for other regions in the state. Analysis of these measurements is used to describe observational constraints on temporal trends in emission sources in the different regions.


Religious beliefs about causes and treatment of epilepsy.
It has been acknowledged that religious and complementary therapies are commonly used among South Asian communities in the UK. However, little is known about their religious beliefs in relation to epilepsy and the type of South Asian therapies that they use to treat the condition. To explore the influences of spiritual and religious beliefs on explanation of the cause of epilepsy, and the choice of treatment in people of South Asian origin who have epilepsy. Qualitative study using interviews with patients, carers, health professionals, and focus groups of people from minority ethnic communities. Bradford and Leeds. Semi-structured individual interviews with 20 Muslims, six Sikhs, and four Hindus with epilepsy; 16 nominated carers (family members, friends); 10 health professionals (specialist GPs, neurologists, specialists nurses, social workers, community GPs); and two focus groups with a total of 16 South Asians without epilepsy. It was found that over half of responders attributed their illness to fate and the will of God, or as punishment for sins of a past life. Some patients had experienced prejudice from people who believed that their epilepsy was contagious. A strong network of traditional healers was found, providing a parallel system of health care in the UK and on the Indian subcontinent. People turned to religiospiritual treatments in desperation for a cure, often under the influence of their families after the perceived failure of Western medicine. Such treatments were viewed as complementary rather than as an alternative to Western medication. Younger people in particular expressed considerable scepticism about the effectiveness of these traditional South Asian treatments. In this study's South Asian sample, patients commonly turned to traditional healers in search of better health. Health professionals should be aware of the belief systems of these patients and understand the types of treatments in common use. Although these treatments might potentially compete with Western health care, they are used as an adjunct rather than a substitute. Patients have a 'healthy' scepticism about the effectiveness of such treatments, and adherence to medical therapy does not appear to be affected.


The study of nursing documentation complexities.
This study aimed to explore complexities in nursing documentation and related factors. Nursing documentation has been one of the most important functions of nurses since the time of Florence Nightingale because it serves multiple and diverse purposes. Current health-care systems require that documentation ensures continuity of care, furnishes legal evidence of the process of care and supports evaluation of quality of patient care. However, nursing documentation has not served such objectives because of its complexities. This study explores nursing documentation complexities and related factors through both qualitative and quantitative methodologies. The study used multiple methods of inquiry: in-depth interviewing; participant observation; nominal group processing; focus group meetings; time and motion study of nursing activities; and auditing of completeness of nursing documentation. Complexities in nursing documentation include three aspects: disruption, incompleteness and inappropriate charting. Related factors that influenced documentation comprised: limited nurses' competence, motivation and confidence; ineffective nursing procedures; and inadequate nursing audit, supervision and staff development. These findings suggest that complexities in nursing documentation require extensive resolution and implicitly dictate strategies for nurse managers and nurses to take part in solving these complicated obstacles.


The clinical effectiveness and cost-effectiveness of home-based, nurse-led health promotion for older people: a systematic review.
In older age, reduction in physical function can lead to loss of independence, the need for hospital and long-term nursing or residential home care, and premature death. Home-visiting programmes for older people, carried out by nurses and other health-care professionals (e.g. occupational therapists and physiotherapists), aim to positively affect health and functional status, and may promote independent functioning of older people. The main research question addressed by this assessment is 'What is the clinical effectiveness and cost-effectiveness of home-based, nurse-led health promotion intervention for older people in the UK?' A comprehensive literature search was undertaken across 12 different databases and research registries from the year 2001 onwards (including MEDLINE, MEDLINE in Process & Other Non-Indexed Citations, EMBASE, Science Citation Index Expanded, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Health Economic Evaluation Database, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects, Cumulative Index to Nursing and Allied Health Literature). Published systematic reviews were also hand searched to identify other trials previously published. Potentially relevant studies were sifted by one reviewer, and inclusion decisions were agreed among the broader research team. The methodological quality of included studies was assessed using the Cochrane Risk of Bias tool. The results of included studies were synthesised using narrative and statistical methods. A separate systematic search was undertaken to identify existing health economic analyses of home-based, nurse-led health promotion programmes. Included studies were critically appraised using a published checklist. Owing to resource constraints, a de novo health economic model was not developed. Eleven studies were included in the systematic review of clinical effectiveness. There was considerable heterogeneity among the studies with respect to the nature of the intervention, the nurses delivering the programmes and the populations in which the interventions were assessed. Overall, the quality of the included studies was good: all but one of the included studies were judged to be at medium or low risk of bias. Meta-analysis of eight studies suggested a statistically significant mortality benefit for the home-based health promotion groups, whereas a meta-analysis of four studies suggested non-significant benefits in terms of fewer falls in the intervention groups than in the control groups. Positive outcomes for home-based, nurse-led health promotion interventions were also reported within individual studies across several other outcomes. Only three economic studies met the criteria for inclusion in the review of cost-effectiveness. This evidence base consists of one non-randomised cost minimisation analysis and two economic evaluations undertaken alongside randomised controlled trials. Two of these studies involved an intervention targeted specifically at patients with a known underlying incurable disease, whereas the third study examined the clinical effectiveness and cost-effectiveness of early discharge in patients with a range of conditions, including fractures, neurological conditions and cardiorespiratory conditions. Each study indicated some likelihood that home-based, nurse-led health promotion may offer cost savings to the NHS and associated sectors, such as social services. However, one study did not report any comparison of health outcomes and instead simply assumed equivalence between the intervention and comparator groups, whereas the other two studies suggested at best a negligible incremental benefit in terms of preference-based health-related quality-of-life measures. The evidence base for clinical effectiveness is subject to considerable heterogeneity. The UK economic evidence base is limited to three studies. On the basis of the evidence included in this systematic review, home-based, nurse-led health promotion may offer clinical benefits across a number of important health dimensions. However, it is generally unclear from the available studies which components of this type of complex intervention contribute towards individual aspects of benefit for older people. Given the limitations of the current evidence base, it remains unclear whether or not home-based health promotion interventions offer good value for money for the NHS and associated sectors. Given the considerable uncertainties in the available evidence base, it is difficult to isolate the key areas in which future research would be valuable or the exact study design required. Although this report does not identify specific studies that should be undertaken, it does set out a number of key considerations for the design of future research in this area. PROSPERO number: CRD42012002133.