Mitochondrial DNA (mtDNA) reveals that female Bechstein's bats live in closed societies.
We present a microgeographic analysis of mitochondrial DNA (mtDNA) in Bechstein's bats using three sources of control region sequence variability, including a novel mtDNA microsatellite, to assess individual relatedness both within and among 10 maternity colonies. Comparison of marker variability among 268 adult females revealed little genetic variability within each colony. However, most colonies were clearly distinguished by colony-specific mitochondrial haplotypes (total n = 28). Low intracolony variability and strong haplotype segregation among colonies, was reflected by an extraordinary high FST of 0.68, indicating a very low intercolony dispersal rate of approximately one female in five generations. Haplotype distribution among 18 solitary males showed that males frequently disperse between colony locations, indicating the absence of dispersal barriers. Bechstein's bat maternity colonies are thus closed groups that comprise 20-40 females probably belonging to only one or, at most, two matrilines. The genetic population structure of Bechstein's bats is in agreement with the hypothesis that females seek familiar and, at least, partially related cooperation partners for raising their young. Alternatively strong philopatry might reflect the importance of profound roost or habitat knowledge for successful reproduction in female Bechstein's bats.


Rotavirus Infection in Children with Acute Gastroenteritis in Iran: A Systematic Review and Meta-analysis.
The recent studies show that Rotavirus is important cause of the acute gastroenteritis. The aim of this review is to estimate the number of Rotavirus infection among Iranian children by performing a systematic review and estimating a pooled data. We performed a systematic literature review in relevant databases including PUBMED, MEDLINE, OVID, SID, MAGIRAN, and IRANMEDEX. Search in databases was done in October 10, 2013. Meta-analysis was performed using the STATA statistical package version 11. We assessed heterogeneity by Q-test and used random model for pooling measures of proportion of Rotavirus infection among Iranian children with diarrhea (and 95% confidence intervals [CI]). Sub group analysis between in-patient and outpatient group were done and publication bias was assessed by Egger and Begg tests. A total of 154 records were identified in our searching. There were 36 studies including a total of 15,368 children with diarrhea. Out of 15,368 children, 6,338 were positive for Rotavirus gastroenteritis. Overall pooled estimate of infection with Rotavirus among cases of gastroenteritis was 0.35 (95% CI, 0.28-0.41). Pooled estimates for hospitalized children and outpatient subgroups were 0.39 (95% CI, 0.30-0.48), and 0.31 (95% CI, 0.23-0.38), respectively. This study supports the importance of Rotavirus in the Iranian population such as common cause of diarrhea among children. Therefore, decision to adopt immunization programs to prevent Rotavirus infection might be helpful in Iran.


Iron deficiency in plants: an insight from proteomic approaches.
Iron (Fe) deficiency chlorosis is a major nutritional disorder for crops growing in calcareous soils, and causes decreases in vegetative growth as well as marked yield and quality losses. With the advances in mass spectrometry techniques, a substantial body of knowledge has arisen on the changes in the protein profiles of different plant parts and compartments as a result of Fe deficiency. Changes in the protein profile of thylakoids from several species have been investigated using gel-based two-dimensional electrophoresis approaches, and the same techniques have been used to investigate changes in the root proteome profiles of tomato (Solanum lycopersicum), sugar beet (Beta vulgaris), cucumber (Cucumis sativus), Medicago truncatula and a Prunus rootstock. High throughput proteomic studies have also been published using Fe-deficient Arabidopsis thaliana roots and thylakoids. This review summarizes the major conclusions derived from these "-omic" approaches with respect to metabolic changes occurring with Fe deficiency, and highlights future research directions in this field. A better understanding of the mechanisms involved in root Fe homeostasis from a holistic point of view may strengthen our ability to enhance Fe-deficiency tolerance responses in plants of agronomic interest.


1H and 31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism.
Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy (1H- and 31P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by 31P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.


Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population.
Evidence suggests that low 25-OH vitamin D 25(OH)D concentrations may increase the risk of several cardiovascular diseases such as hypertension, peripheral vascular disease, diabetes mellitus, obesity, myocardial infarction, heart failure and cardiovascular mortality. Recent studies suggested a possible relationship between vitamin D deficiency and increased carotid intima-media wall thickness and vascular calcification. We hypothesized that low 25(OH)D may be associated with coronary atherosclerosis and coronary plaque burden and composition, and investigated the relationship between serum vitamin D levels and coronary atherosclerosis, plaque burden or structure, in young adult patients by using dual-source 128x2 slice coronary computed tomography angiography (CCTA). We included 98 patients with coronary atherosclerosis and 110, age and gender matched, subjects with normal findings on CCTA examinations. Patients with subclinical atherosclerosis had significantly higher serum total cholesterol, triglycerides, hs-CRP, uric acid, HbA1c and creatinine levels and lower serum 25(OH)D levels in comparison with controls. There was no significant correlation between 25(OH)D and plaque morphology. There was also a positive relationship between 25(OH)D and plaque burden of coronary atherosclerosis. In multivariate analysis, coronary atherosclerosis was associated high hs-CRP (adjusted OR: 2.832), uric acid (adjusted OR: 3.671) and low 25(OH)D (adjusted OR: 0.689). Low levels of 25(OH)D were associated with coronary atherosclerosis and plaque burden, but there was no significant correlation between 25(OH)D and plaque morphology.


Incorporation of pazopanib in maintenance therapy of ovarian cancer.
Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy. Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators. Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%). Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).


The science behind percutaneous hemodynamic support: a review and comparison of support strategies.
Patients in a variety of cardiovascular disease states may benefit from temporary percutaneous cardiac support, including those in acute decompensated heart failure, fulminant myocarditis, acute myocardial infarction with or without cardiogenic shock and those undergoing high-risk percutaneous coronary intervention. The ideal percutaneous cardiac support device is safe, easy to use and versatile enough to meet the needs of various clinical situations and patient cohorts. In addition, it should provide maximal hemodynamic support and protection against myocardial ischemia. With these goals in mind, the scientific principles that govern hemodynamic effectiveness and myocardial protection as they pertain to acute support devices are reviewed.


Bioinspired dual-stiffness origami.
Origami manufacturing has led to considerable advances in the field of foldable structures with innovative applications in robotics, aerospace, and metamaterials. However, existing origami are either load-bearing structures that are prone to tear and fail if overloaded or resilient soft structures with limited load capability. In this manuscript, we describe an origami structure that displays both high load bearing and high resilience characteristics. The structure, which is inspired by insect wings, consists of a prestretched elastomeric membrane, akin to the soft resilin joints of insect wings, sandwiched between rigid tiles, akin to the rigid cuticles of insect wings. The dual-stiffness properties of the proposed structure are validated by using the origami as an element of a quadcopter frame that can withstand aerodynamic forces within its flight envelope but softens during collisions to avoid permanent damage. In addition, we demonstrate an origami gripper that can be used for rigid grasping but softens to avoid overloading of the manipulated objects.


Variation in resistance of cells from inbred strains of mice to herpes simplex virus type 1.
By several criteria, replication of herpes simplex virus type 1 (HSV-1) in primary cell cultures from inbred strains of mice resistant (R) to this virus was less than in cultures from susceptible (S) strains. The difference was not obviously related to less efficient adsorption, to more efficient production of interferon or to a larger number of lysosomes. Except at high multiplicities of infection, cells from the F1 progeny of a cross between an R and an S strain replicated virus as well as cells from the S parent; this contrasts with strain-related resistance to intraperitoneal inoculation in vivo, which is inherited as a dominant characteristic. It is suggested that diminished ability of structural cells to replicate HSV-1 may contribute to resistance in the intact animal.


Primary idiopathic chylopericardium associated with cervicomediastinal cystic hygroma.
Chylopericardium is a rare clinical entity in which chylous fluid accumulates in the pericardial cavity. We report a case of primary idiopathic chylopericardium associated with multiple, small cervicomediastinal cystic hygromas occurring in an asymptomatic 43-year-old woman with no history of trauma, thoracic surgery, malignancy, infection or tuberculosis. Echocardiography showed a large amount of pericardial effusions and pericardial fluid analysis revealed inappropriately elevated triglyceride. We did not demonstrate communication between the thoracic duct and the pericardial sac by lymphangiography and chest computed tomography. She successfully responded to 30 days of continuous pericardial drainage and 15 days of a medium-chain triglyceride diet after 30 days of total parenteral nutrition. Follow-up echocardiography 6 months after treatment commencement showed a minimal reaccumulation of pericardial fluid without symptom. We conclude that if a patient is asymptomatic and can well tolerate daily life, surgery including pericardiectomy or ligation of the thoracic duct is not necessarily required.


Prevalence of autism spectrum disorders--autism and developmental disabilities monitoring network, 14 sites, United States, 2002.
Data from a population-based, multisite surveillance network were used to determine the prevalence of autism spectrum disorders (ASDs) among children aged 8 years in 14 areas of the United States and to describe the characteristics of these children. 2002. Children aged 8 years were identified as having an ASD through screening and abstraction of evaluation records at health facilities for all 14 sites and through information from psychoeducational evaluations for special education services for 10 of the 14 sites. Case status was determined through clinician review of data abstracted from the records. Children whose parent(s) or legal guardian(s) resided in the respective areas in 2002 and whose records documented behaviors consistent with the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria for autistic disorder; pervasive developmental disorder, not otherwise specified; or Asperger disorder were classified as having ASDs. For 2002, of 407,578 children aged 8 years in the 14 surveillance areas, 2,685 (0.66%) were identified as having an ASD. ASD prevalence per 1,000 children aged 8 years ranged from 3.3 (Alabama) to 10.6 (New Jersey), with the majority of sites ranging from 5.2 to 7.6 (overall mean: 6.6 [i.e., one of every 152 children across all sites). ASD prevalence was significantly lower than all other sites in Alabama (p<0.001) and higher in New Jersey (p<0.0001). ASD prevalence varied by identification source, with higher average prevalence for ASDs in sites with access to health and education records (mean: 7.2) compared with sites with health records only (mean: 5.1). Five sites identified a higher prevalence of ASDs for non-Hispanic white children than for non-Hispanic black children. The ratio of males to females ranged from 3.4:1.0 in Maryland, South Carolina, and Wisconsin to 6.5:1.0 in Utah. The majority of children were receiving special education services at age 8 years and had a documented history of concerns regarding their development before age 3 years. However, the median age of earliest documented ASD diagnosis was much later (range: 49 months [Utah]--66 months [Alabama]). The proportion of children with characteristics consistent with the criteria for an ASD classification who had a previously documented ASD classification varied across sites. In the majority of sites, females with an ASD were more likely than males to have cognitive impairment. For the six sites for which prevalence data were available from both 2000 and 2002, ASD prevalence was stable in four sites and increased in two sites (17% in Georgia and 39% in West Virginia). Results from the second report of a U.S. multisite collaboration to monitor ASD prevalence demonstrated consistency of prevalence in the majority of sites, with variation in two sites. Prevalence was stable in the majority of sites for which 2 years of data were available, but an increase in West Virginia and a trend toward an increase in Georgia indicate the need for ongoing monitoring of ASD prevalence. These ASD prevalence data provide the most complete information on the prevalence of the ASDs in the United States to date. The data confirm that ASD prevalence is a continuing urgent public health concern affecting an approximate average of one child in every 150 and that efforts are needed to improve early identification of ASDs.


Pursuing Excellence: The Power of Selection Science to Provide Meaningful Data and Enhance Efficiency in Selecting Surgical Trainees.
As current screening methods for selecting surgical trainees are receiving increasing scrutiny, development of a more efficient and effective selection system is needed. We describe the process of creating an evidence-based selection system and examine its impact on screening efficiency, faculty perceptions, and improving representation of underrepresented minorities. The program partnered with an expert in organizational science to identify fellowship position requirements and associated competencies. Situational judgment tests, personality profiles, structured interviews, and technical skills assessments were used to measure these competencies. The situational judgment test and personality profiles were administered online and used to identify candidates to invite for on-site structured interviews and skills testing. A final rank list was created based on all data points and their respective importance. All faculty completed follow-up surveys regarding their perceptions of the process. Candidate demographic and experience data were pulled from the application website. Fifty-five of 72 applicants met eligibility requirements and were invited to take the online assessment, with 50 (91%) completing it. Average time to complete was 42 ± 12 minutes. Eighteen applicants (35%) were invited for on-site structured interviews and skills testing-a greater than 50% reduction in number of invites compared to prior years. Time estimates reveal that the process will result in a time savings of 68% for future iterations, compared to traditional methodologies. Fellowship faculty (N = 5) agreed on the value and efficiency of the process. Underrepresented minority candidates increased from an initial 70% to 92% being invited for an interview and ranked using the new screening tools. Applying selection science to the process of choosing surgical trainees is feasible, efficient, and well-received by faculty for making selection decisions.


Is refreshing in working memory impaired in older age? Evidence from the retro-cue paradigm.
Impairments in refreshing have been suggested as one source of working memory (WM) deficits in older age. Retro-cues provide an important method of investigating this question: a retro-cue guides attention to one WM item, thereby arguably refreshing it and increasing its accessibility compared with a no-cue baseline. In contrast to the refreshing deficit hypothesis, intact retro-cue benefits have been found in older adults. Refreshing, however, is assumed to boost not one but several WM representations when sequentially applied to them. Hence, intact refreshing requires the flexible switching of attention among WM items. So far, it remains an open question whether older adults show this flexibility. Here, we investigated whether older adults can use multiple cues to sequentially refresh WM representations. Younger and older adults completed a continuous-color delayed-estimation task, in which the number of retro-cues (0, 1, or 2) presented during the retention interval was manipulated. The results showed a similar retro-cue benefit for younger and older adults, even in the two-cue condition in which participants had to switch attention between items to refresh representations in WM. These findings suggest that the capacity to use cues to refresh information in visual WM may be preserved with age.


Prioritization and the elusive effect on welfare - a Norwegian health care reform revisited.
The Faster Return to Work (FRW) scheme that Norwegian authorities implemented in 2007 is an example of a policy that builds on the human capital approach. The main idea behind the scheme is that long waiting times for hospital treatment lead to unnecessarily long periods of absence from work. To achieve a reduction in average sickness absence duration, the allocation of FRW funds and new treatment capacity is exclusively aimed at people on sick leave. Many countries have allocated funds to reduce waiting times for hospital treatment and research shows that more resources allocated to the hospital sector can reduce waiting times. Our results support this as the FRW scheme significantly reduces waiting times. However, on average the reduction in waiting times is not transformed into an equally large reduction in the sickness absence period. We find significant difference in the effects of FRW on length of sick leave between surgical and non-surgical patients though. The duration of sick leave for FRW patients undergoing surgical treatment is approximately 14 days shorter than for surgical patients on the regular waiting list. We find no significant effect of the scheme on length of sick leave for non-surgical patients. In sum, our welfare analysis indicates that prioritization of the kind that the FRW scheme represents is not as straightforward as one would expect. The FRW scheme costs more than it contributes in reduced productivity loss. We base our analyses on several different econometric methods using register data on approximately 13,500 individuals over the period 2007-2008.


An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study.
Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.


Advantages and Disadvantages in Image Processing with Free Software in Radiology.
Currently, there are sophisticated applications that make it possible to visualize medical images and even to manipulate them. These software applications are of great interest, both from a teaching and a radiological perspective. In addition, some of these applications are known as Free Open Source Software because they are free and the source code is freely available, and therefore it can be easily obtained even on personal computers. Two examples of free open source software are Osirix Lite® and 3D Slicer®. However, this last group of free applications have limitations in its use. For the radiological field, manipulating and post-processing images is increasingly important. Consequently, sophisticated computing tools that combine software and hardware to process medical images are needed. In radiology, graphic workstations allow their users to process, review, analyse, communicate and exchange multidimensional digital images acquired with different image-capturing radiological devices. These radiological devices are basically CT (Computerised Tomography), MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), etc. Nevertheless, the programs included in these workstations have a high cost which always depends on the software provider and is always subject to its norms and requirements. With this study, we aim to present the advantages and disadvantages of these radiological image visualization systems in the advanced management of radiological studies. We will compare the features of the VITREA2® and AW VolumeShare 5® radiology workstation with free open source software applications like OsiriX® and 3D Slicer®, with examples from specific studies.


3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry.
A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.


Cultural, social and intrapersonal factors associated with clusters of co-occurring health-related behaviours among adolescents.
Adverse health-related behaviours (HRBs) have been shown to co-occur in adolescents. Evidence lacks on factors associated with these co-occurring HRBs. The Theory of Triadic Influence (TTI) offers a route to categorize these determinants according to type (social, cultural and intrapersonal) and distance in the causal pathway (ultimate or distal). Our aims were to identify cultural, social and intrapersonal factors associated with co-occurring HRBs and to assess the relative importance of ultimate and distal factors for each cluster of co-occurring HRBs. Respondents concerned a random sample of 898 adolescents aged 12-18 years, stratified by age, sex and educational level of head of household. Data were collected via face-to-face computer-assisted interviewing and internet questionnaires. Analyses were performed for young (12-15 years) and late (16-18 years) adolescents regarding two and three clusters of HRB, respectively. For each cluster of HRBs (e.g. smoking, delinquency), associated factors were found. These accounted for 27 to 57% of the total variance per cluster. Factors came in particular from the intrapersonal stream of the TTI at the ultimate level and the social stream at the distal level. Associations were strongest for parenting practices, risk behaviours of friends and parents and self-control. Results of this study confirm that it is possible to identify a selection of cultural, social and intrapersonal factors associated with co-occurring HRBs among adolescents.


Esther McCready, RN: Nursing Advocate for Civil Rights
More than a decade before the Civil Rights Act of 1964, as an African American teenager from Baltimore, Maryland, Esther McCready challenged the discriminatory admissions policies of the University of Maryland School of Nursing (UMSON). The article explores nurse advocacy and how Esther McCready advocated for herself and greater racial equity in nursing education during a time of civil rights turmoil. Her actions eventually resulted in the formation of numerous schools of nursing for African Americans across the south. This article recounts McCready's early life experiences and the powerful impact her actions had on creating educational options for nurses during a time when they were severely limited for African American women, including discussion of her student days at UMSON and her journey after nursing school. A review of pertinent legal cases and policies related to segregation and integration of higher education in the mid-twentieth century is presented, along with details of McCready's continued education and advocacy.


Genetic Knowledge within a National Australian Sample: Comparisons with Other Diverse Populations.
Genetic knowledge, which plays important functions in our understanding of science, health, social groupings, and even behaviour, has been evaluated in past studies with various populations. This wide reach of genetics means that different types of items are used to assess genetic knowledge, which restricts meaningful comparisons across time- and locale-based studies. The present study addresses this limitation by recruiting an Australia-wide sample and evaluating their genetic knowledge using items sourced from four diverse samples. Seven hundred and eighty Australians completed a variety of items assessing their genetic knowledge as well as several demographic indicators. The results show superior overall genetic knowledge in the current sample compared with previous samples. Additionally, the study finds that genetic knowledge about health and illness seems to be the most accurate, whereas such knowledge about social categorisations and behaviours seems to be the most error-prone. In the current sample, being a female and having interest in genetics were positive predictors of genetic knowledge; surprisingly educational attainment was not a significant predictor. Compared with previous surveys, the current sample showed significantly better genetic knowledge. However, certain areas that relate to public understating still indicate rampant misperceptions.


Genetic diversity of feline immunodeficiency virus: dual infection, recombination, and distinct evolutionary rates among envelope sequence clades.
For the rapid genetic analysis of feline immunodeficiency virus (FIV), we developed a heteroduplex mobility assay (HMA) that utilizes a PCR-amplified fragment of the FIV envelope gene spanning the third and fourth variable regions of the envelope surface protein coding sequence. Viral sequences were successfully amplified from blood specimens from 98 naturally infected cats from Australia, Canada, Germany, Italy, South Africa, and the United States. Eighty were clearly assignable to the A or B envelope sequence subtypes. Three belonged to subtype C, one was dually infected with viruses harboring the A and B env subtypes, and several were categorized as outliers to any of the established subtypes or as probable intersubtype recombinants. Some geographic clustering was evident, with subtypes A and B found in greater frequency in the western and eastern regions of the United States, respectively. Subtypes A, B, and C were found on more than one continent, and countries with more than two samples analyzed contained at least two subtypes. The broadest representation of subtypes was found in Munich, Germany, where three subtypes and one virus that was not classifiable by HMA were found. Thirteen samples were selected for DNA sequence determination over the same region of env used for HMA. Analysis of all available FIV env sequences from this and previous studies revealed the existence of recombinant viruses generated from subtype A/B, B/D, and A/C envelope gene sequences. Subtype A env sequences were less diverse than subtype B sequences, although both groups had well-supported clusters. Furthermore, the mutational pattern giving rise to diversification in the two subtypes differed, with the subtype A viruses showing half as many synonymous site mutations compared to subtype B yet showing similar levels of nonsynonymous site changes. These results are consistent with the hypothesis that FIV-B is an older virus group and is possibly more host adapted than FIV-A.


Proteolysis of cystatin C by cathepsin D in the breast cancer microenvironment.
The aspartic protease cathepsin D, a poor prognostic indicator of breast cancer, is abundantly secreted as procathepsin D by human breast cancer cells and self-activates at low pH in vitro, giving rise to catalytically active cathepsin D. Due to a lower extracellular pH in tumor microenvironments compared to normal tissues, cathepsin D may cleave pathophysiological substrates contributing to cancer progression. Here, we show by yeast 2-hybrid and degradomics analyses that cystatin C, the most potent natural secreted inhibitor of cysteine cathepsins, both binds to and is a substrate of extracellular procathepsin D. The amount of cystatin C in the extracellular environment is reduced in the secretome of mouse embryonic fibroblasts stably transfected with human cathepsin D. Cathepsin D extensively cleaved cystatin C in vitro at low pH. Cathepsin D secreted by breast cancer cells also processed cystatin C at the pericellular pH of tumors and so enhancing extracellular proteolytic activity of cysteine cathepsins. Thus, tumor derived cathepsin D assists breast cancer progression by reducing cystatin C activity, which, in turn, enhances cysteine cathepsin proteolytic activity, revealing a new link between protease classes in the protease web.


Anti-ganglioside antibodies can bind peripheral nerve nodes of Ranvier and activate the complement cascade without inducing acute conduction block in vitro.
The neurophysiological effects of nine neuropathy-associated human anti-ganglioside antisera, three monoclonal antibodies to ganglioside GM1 (GM1) and of the cholera toxin B subunit (a GM1 ligand) were studied on mouse sciatic nerve in vitro. GM1 antisera and monoclonal antibodies from patients with chronic motor neuropathies and Guillain-Barre syndrome, and GQ1b/ disialosyl antisera and monoclonal antibodies from patients with chronic ataxic neuropathies and Miller Fisher syndrome were studied. In vitro recording, for up to 6 h, of compound nerve action potentials, latencies, rise times and stimulus thresholds from isolated desheathed sciatic nerve was performed in the presence of antiganglioside antibodies and fresh human serum as an additional source of complement. No changes were observed over this time course, with 4-6 h values for all electrophysiological parameters being within 15% of the starting values for both normal and antibody containing sera and for the cholera toxin B subunit. Parallel experiments on identically prepared desheathed nerves performed with 0.5 nM saxitoxin led to complete conduction block within 10 min of application. Under identical conditions to those used for electrophysiological recordings, quantitative immunohistological evaluation revealed a significant increase in IgM (immunoglobulin M) deposition at nodes of Ranvier from 5.3+/-3.1% to 28.7+/-8.4% (mean+/-SEM) of desheathed nerves exposed to three normal and three antibody containing sera, respectively (P < 0.03). Complement activation was seen at 100% of normal and 79% of disease-associated IgM positive nodes of Ranvier. These data indicate that anti-ganglioside antibodies can diffuse into a desheathed nerve, bind to nodes of Ranvier and fix complement in vitro without resulting in any overt physiological deterioration of the nerve over 4-6 h. This suggests that the node of Ranvier is relatively resistant to acute antiganglioside antibody mediated injury over this time scale and that anti-ganglioside antibodies and the cholera toxin B subunit are unlikely to have major direct pharmacological effects on nodal function, at least in comparison with the effect of saxitoxin. This in vitro sciatic nerve model appears of limited use for analysing electrophysiologically the effects of anti-ganglioside antibodies on nerve function, possibly because its short-term viability and isolation from circulating systemic factors do not permit the evolution of an inflammatory lesion of sufficient magnitude to induce overt electrophysiological abnormalities. In vivo models may be more suitable for identifying the effects of these antibodies on nerve conduction.


Mechanisms of attention for appetitive and aversive outcomes in Pavlovian conditioning.
Different mechanisms of attention controlling learning have been proposed in appetitive and aversive conditioning. The aim of the present study was to compare attention and learning in a Pavlovian conditioning paradigm using visual stimuli of varying predictive value of either monetary reward (appetitive conditioning; 10p or 50p) or blast of white noise (aversive conditioning; 97 dB or 102 dB). Outcome values were matched across the two conditions with regard to their emotional significance. Sixty-four participants were allocated to one of the four conditions matched for age and gender. All participants underwent a discriminative learning task using pairs of visual stimuli that signalled a 100%, 50%, or 0% probability of receiving an outcome. Learning was measured using a 9-point Likert scale of expectancy of the outcome, while attention using an eyetracker device. Arousal and emotional conditioning were also evaluated. Dwell time was greatest for the full predictor in the noise groups, while in the money groups attention was greatest for the partial predictor over the other two predictors. The progression of learning was the same for both groups. These findings suggest that in aversive conditioning attention is driven by the predictive salience of the stimulus while in appetitive conditioning attention is error-driven, when emotional value of the outcome is comparable.


Cascading Failures as Continuous Phase-Space Transitions.
In network systems, a local perturbation can amplify as it propagates, potentially leading to a large-scale cascading failure. Here we derive a continuous model to advance our understanding of cascading failures in power-grid networks. The model accounts for both the failure of transmission lines and the desynchronization of power generators and incorporates the transient dynamics between successive steps of the cascade. In this framework, we show that a cascade event is a phase-space transition from an equilibrium state with high energy to an equilibrium state with lower energy, which can be suitably described in a closed form using a global Hamiltonian-like function. From this function, we show that a perturbed system cannot always reach the equilibrium state predicted by quasi-steady-state cascade models, which would correspond to a reduced number of failures, and may instead undergo a larger cascade. We also show that, in the presence of two or more perturbations, the outcome depends strongly on the order and timing of the individual perturbations. These results offer new insights into the current understanding of cascading dynamics, with potential implications for control interventions.


Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens.
Long-term selection experiments provide a powerful approach to gain empirical insights into adaptation, allowing researchers to uncover the targets of selection and infer their contributions to the mode and tempo of adaptation. Here we implement a pooled genome re-sequencing approach to investigate the consequences of 39 generations of bidirectional selection in White Leghorn chickens on a humoral immune trait: antibody response to sheep red blood cells. We observed wide genome involvement in response to this selection regime. Many genomic regions were highly differentiated resulting from this experimental selection regime, an involvement of up to 20% of the chicken genome (208.8 Mb). While genetic drift has certainly contributed to this, we implement gene ontology, association analysis and population simulations to increase our confidence in candidate selective sweeps. Three strong candidate genes, MHC, SEMA5A and TGFBR2, are also presented. The extensive genomic changes highlight the polygenic genetic architecture of antibody response in these chicken populations, which are derived from a common founder population, demonstrating the extent of standing immunogenetic variation available at the onset of selection.


Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro.
An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.


Single crystal structure and opto-electronic properties of oxidized Spiro-OMeTAD.
Single crystals of Spiro(TFSI)2 were grown, the optical and electronic properties were characterized and compared with neutral Spiro-OMeTAD. Density-functional theory was used to get insights into binding and band structure properties. The flat valence bands indicate a rather limited orbital overlap in Spiro(TFSI)2.


Evaluating complex interventions and health technologies using normalization process theory: development of a simplified approach and web-enabled toolkit.
Normalization Process Theory (NPT) can be used to explain implementation processes in health care relating to new technologies and complex interventions. This paper describes the processes by which we developed a simplified version of NPT for use by clinicians, managers, and policy makers, and which could be embedded in a web-enabled toolkit and on-line users manual. Between 2006 and 2010 we undertook four tasks. (i) We presented NPT to potential and actual users in multiple workshops, seminars, and presentations. (ii) Using what we discovered from these meetings, we decided to create a simplified set of statements and explanations expressing core constructs of the theory (iii) We circulated these statements to a criterion sample of 60 researchers, clinicians and others, using SurveyMonkey to collect qualitative textual data about their criticisms of the statements. (iv) We then reconstructed the statements and explanations to meet users' criticisms, embedded them in a web-enabled toolkit, and beta tested this 'in the wild'. On-line data collection was effective: over a four week period 50/60 participants responded using SurveyMonkey (40/60) or direct phone and email contact (10/60). An additional nine responses were received from people who had been sent the SurveyMonkey form by other respondents. Beta testing of the web enabled toolkit produced 13 responses, from 327 visits to http://www.normalizationprocess.org. Qualitative analysis of both sets of responses showed a high level of support for the statements but also showed that some statements poorly expressed their underlying constructs or overlapped with others. These were rewritten to take account of users' criticisms and then embedded in a web-enabled toolkit. As a result we were able translate the core constructs into a simplified set of statements that could be utilized by non-experts. Normalization Process Theory has been developed through transparent procedures at each stage of its life. The theory has been shown to be sufficiently robust to merit formal testing. This project has provided a user friendly version of NPT that can be embedded in a web-enabled toolkit and used as a heuristic device to think through implementation and integration problems.


Cochlear Fibrocyte and Osteoblast Lineages Expressing Type 2 Deiodinase Identified with a Dio2CreERt2 Allele.
Type 2 deiodinase (Dio2) amplifies levels of 3,5,3'-L-triiodothyronine (T3), the active form of thyroid hormone, and is essential for cochlear maturation and auditory development. However, cellular routes for endocrine signaling in the compartmentalized, anatomically complex cochlea are little understood. Dio2 generates T3 from thyroxine (T4), a more abundant thyroid hormone precursor in the circulation, and is dramatically induced in the cochlea before the onset of hearing. The evidence implies that specific Dio2-expressing cell types critically mediate T3 signaling but these cell types are poorly defined because Dio2 is expressed transiently at low levels. Here, using a Dio2CreERt2 knockin that activates a fluorescent reporter, we define Dio2-expressing cochlear cell types at high resolution in male or female mice. Dio2-positive cells were detected in vascularized supporting tissues but not in avascular internal epithelia, indicating segregation of T3-generating and T3-responding tissues. In the spiral ligament and spiral limbus, Dio2-positive fibrocytes clustered around vascular networks that convey T4 into cochlear tissues. In the otic capsule, Dio2-positive osteoblasts localized at cartilage surfaces as the bony labyrinth matures. We corroborated the identities of Dio2-positive lineages by RNA-sequencing of individual cells. The results suggest a previously unrecognized role for fibrocytes in mediating hormonal signaling. We discuss a model whereby fibrocytes mediate paracrine-like control of T3 signaling to the organ of Corti and epithelial target tissues.


Estrogen receptor α splice variant TADDI in the human supraoptic nucleus: an effect on neuronal size and changes in pneumonia.
Estrogens mediate various effects in the brain not only via classical estrogen receptors (ERs) but also through their splice variants. We showed earlier that the ERα splice variant TADDI is abundantly expressed in the human hypothalamic supraoptic nucleus (SON). In the present study we aimed at determining a possible effect of TADDI on human SON neuronal morphometric parameters in 58 control patients from 20 to 94 years old and in 26 patients with Alzheimer's disease (AD) aged 54-94 years old. The size of neuronal nuclear and perikaryal profiles was determined as measure of the neuronal metabolic activity in relation to the intensity of TADDI immunocytochemical staining. The size of SON neuronal nuclei and perikarya were also measured with respect to the wild type (wt) ERα nuclear staining in the group of 11 elderly patients. Independently of gender, age or AD status SON neuronal nuclei and perikarya were significantly smaller in neurons with moderate and strong TADDI staining than in neurons that did not express this ERα splice variant. On the contrary, neuronal nuclei and perikarya were considerably larger in SON neurons with moderate and strong nuclear staining for wt ERα as compared to neurons that showed an absence of the classic receptor. It is noteworthy that TADDI immunoreactivity was increased in control patients with pneumonia and/or respiratory insufficiency. We showed for the first time the association of the ERα splice variant TADDI with neuronal morphometric parameters in the human postmortem brain tissue.


Health and Grandparent-Grandchild Well-Being: One-Year Longitudinal Findings for Custodial Grandfamilies.
Comparatively little longitudinal data exist focusing on grandparent caregiving, to say nothing of health's impact over time on grandparent and grandchild well-being. Accordingly, the present study explored relationships among grandparent caregiver physical health, well-being, and adjustment, as well as with grandchild well-being across a 1-year period. Participants were 79 grandparents who had full-time responsibility for their grandchildren. Measures of grandparent physical health, well-being, and grandchild well-being were completed across two assessments, 1 year apart. Cross-lagged analyses exploring potential causality over time suggested that with one exception, the relationships between health and well-being appeared to be bidirectional. In general, these longitudinal data indicate that better perceived health may provide an adaptive advantage for both grandparent caregivers and their grandchildren, yet also underscore to the potentially causal role that proactivity in the face of adversity plays in the maintenance and improvement of grandparent caregiver health over time.


The validity of new memory complaints in the elderly.
To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. Prospective cohort. Longitudinal, community-based study of aging and dementia. One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.


Morphological, Histological, and Molecular Description of Unicauda fimbrethilae n. sp. (Cnidaria: Myxosporea: Myxobolidae) from the Intestinal Tract of Channel Catfish Ictalurus punctatus.
The channel catfish Ictalurus punctatus is a known host for 10 species of Henneguya, but few other myxozoan genera are described from this species. Unicauda is a genus of myxozoan parasites within the family Myxobolidae that consists of 10 valid species from freshwater fish. Herein, we describe a novel species of Unicauda from the intestinal tract of farm-raised channel catfish in Mississippi. Myxospores were consistent with the genus Unicauda but exhibited a unique branching at the terminal end of the caudal process that has not previously been reported. Myxospores measured 90.39 ± 14.97 μm (mean ± SD; range = 70.88-126.02 μm) in total length. The spherical spore body measured 7.31 ± 0.26 μm (6.75-7.84 μm) in length and 7.01 ± 0.63 μm (6.1-8.01 μm) in width. The 2 polar capsules measured 3.45 ± 0.33 μm (3.02-4.03 μm) in length and 2.65 ± 0.32 μm (2.18-3.11 μm) in width. The single caudal process measured 82.98 ± 14.97 μm (63.39-118.63 μm) in length from the base of the spore body to the end of the most terminal projection. Terminal projections measured 26.83 ± 8.8 μm (12.34-42.29 μm) in length and 0.95 ± 0.23 μm (0.52-1.6 μm) in width. The 18S rRNA gene sequence obtained did not match any published sequences. Given the uniqueness of the myxospore morphology, histological presentation, and gene sequence data, we describe this as an unreported species, Unicauda fimbrethilae n. sp.


Detection of Genomic Structural Variants from Next-Generation Sequencing Data.
Structural variants are genomic rearrangements larger than 50 bp accounting for around 1% of the variation among human genomes. They impact on phenotypic diversity and play a role in various diseases including neurological/neurocognitive disorders and cancer development and progression. Dissecting structural variants from next-generation sequencing data presents several challenges and a number of approaches have been proposed in the literature. In this mini review, we describe and summarize the latest tools - and their underlying algorithms - designed for the analysis of whole-genome sequencing, whole-exome sequencing, custom captures, and amplicon sequencing data, pointing out the major advantages/drawbacks. We also report a summary of the most recent applications of third-generation sequencing platforms. This assessment provides a guided indication - with particular emphasis on human genetics and copy number variants - for researchers involved in the investigation of these genomic events.


[Violence between couples].
This article describes variables related to different forms of violence in couples. These variables have been organized in a theoretical model that takes into account cultural factors, sociodemographic and family characteristics, attitudes, and other variables defined as inhibitors and facilitators of violence in conflict situations. For the ACTIVA project, a representative sample consisting of 10,821 people was interviewed in eight cities. For this research on couples, 6,184 of those responses were taken into consideration, from persons who were in a marriage or an unmarried relationship during the year before the interview. The data were obtained from verbal responses to a questionnaire completed in the interviewees' residences. The variables that were clearly associated with couples violence were: socioeconomic level (the fewer the economic resources, the greater the violence), gender (women reported both using and receiving more violence than men did, although the actual level of violence was similar), age (there was more violence between younger people), marital status (there was more violence between unmarried persons), childhood abuse (those most abused in childhood), excessive alcohol consumption (those who have gotten drunk), holding attitudes justifying violence, and having fewer skills to deal with conflicts. Acts of violence, which both men and women commit in relationships, originate in the socialization process, both through the practice of abuse as well as the transmission of values that lead to attitudes justifying violence. A number of things could help markedly reduce the levels of couples violence, including a balance of power between the two persons in the relationship, a modification of attitudes, an improvement in conflict-resolution skills, and a reduction in stress-producing factors.


Effective function annotation through catalytic residue conservation.
Because of the extreme impact of genome sequencing projects, protein sequences without accompanying experimental data now dominate public databases. Homology searches, by providing an opportunity to transfer functional information between related proteins, have become the de facto way to address this. Although a single, well annotated, close relationship will often facilitate sufficient annotation, this situation is not always the case, particularly if mutations are present in important functional residues. When only distant relationships are available, the transfer of function information is more tenuous, and the likelihood of encountering several well annotated proteins with different functions is increased. The consequence for a researcher is a range of candidate functions with little way of knowing which, if any, are correct. Here, we address the problem directly by introducing a computational approach to accurately identify and segregate related proteins into those with a functional similarity and those where function differs. This approach should find a wide range of applications, including the interpretation of genomics/proteomics data and the prioritization of targets for high-throughput structure determination. The method is generic, but here we concentrate on enzymes and apply high-quality catalytic site data. In addition to providing a series of comprehensive benchmarks to show the overall performance of our approach, we illustrate its utility with specific examples that include the correct identification of haptoglobin as a nonenzymatic relative of trypsin, discrimination of acid-d-amino acid ligases from a much larger ligase pool, and the successful annotation of BioH, a structural genomics target.


Validated Method for the Characterization and Quantification of Extractable and Nonextractable Ellagitannins after Acid Hydrolysis in Pomegranate Fruits, Juices, and Extracts.
Pomegranates are one of the main highly valuable sources of ellagitannins. Despite the potential health benefits of these compounds, reliable data on their content in pomegranates and derived extracts and food products is lacking, as it is usually underestimated due to their complexity, diversity, and lack of commercially available standards. This study describes a new method for the analysis of the extractable and nonextractable ellagitannins based on the quantification of the acid hydrolysis products that include ellagic acid, gallic acid, sanguisorbic acid dilactone, valoneic acid dilactone, and gallagic acid dilactone in pomegranate samples. The study also shows the occurrence of ellagitannin C-glycosides in pomegranates. The method was optimized using a pomegranate peel extract. To quantify nonextractable ellagitannins, freeze-dried pomegranate fruit samples were directly hydrolyzed with 4 M HCl in water at 90 °C for 24 h followed by extraction of the pellet with dimethyl sulfoxide/methanol (50:50, v/v). The method was validated and reproducibility was assessed by means of an interlaboratory trial, showing high reproducibility across six laboratories with relative standard deviations below 15%. Their applicability was demonstrated in several pomegranate extracts, different parts of pomegranate fruit (husk, peels, and mesocarp), and commercial juices. A large variability has been found in the ellagitannin content (150-750 mg of hydrolysis products/g) and type (gallagic acid/ellagic acid ratios between 4 and 0.15) of the 11 pomegranate extracts studied.


The Emergent Literacy Skills of Preschool Children with Autism Spectrum Disorder.
A high percentage of school-age students with autism spectrum disorder (ASD) have reading comprehension difficulties leading to academic disadvantage. These difficulties may be related to differences in children's emergent literacy development in the preschool years. In this study, we examined the relationship between emergent literacy skills, broader cognitive and language ability, autism severity, and home literacy environment factors in 57 preschoolers with ASD. The children showed strengths in code-related emergent literacy skills such as alphabet knowledge, but significant difficulties with meaning-related emergent literacy skills. There was a significant relationship between meaning-related skills, autism severity, general oral language skills, and nonverbal cognition. Identification of these meaning-related precursors will guide the targets for early intervention to help ensure reading success for students with ASD.


Observational Study Design in Veterinary Pathology, Part 1: Study Design.
Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods.


Selection of surgical intervention for congenital dacryocystocele.
To evaluate the surgical intervention and its effect on congenital dacryocystocele. A total of 531 children with congenital dacryocystocele admitted to the Department of Ophthalmology of Beijing Children's Hospital, Shanghai Aier Eye Hospital, Nanjing Aier Eye Hospital, and the First Affiliated Hospital of Jinzhou Medical University between January 2007 and January 2017 were retrospectively analyzed. A total of 531 patients were followed up for 3-24 months, with an average of 13.3 months. No serious intraoperative complications (such as bleeding and tissue damage) and postoperative complications (bleeding, infection, and hole atresia) were found. We classified the outcomes into three categories based on the signs (overflowing tears and empyema) and objective routine follow-up by endoscopy. Cure indicated that mass, overflow of tears, and breathing difficulties disappeared, and 81.5% cases (433/531) were postoperatively cured. Improvement indicated disappearance of mass, overflow empyema, and the presence of residual tears (due to trocar and tears puncture), and 18.5% cases (98/531) were postoperatively improved. Unhealed indicated overflowing pus and tears, and 0% cases did not heal after surgery. Nasal endoscopic surgery is relatively safe, with high success rate for treatment of congenital dacryocystocele. Systematic training is required to promote the application of nasal endoscopy, so that more ophthalmologists can learn this technique.


T cell proliferative response to type II collagen in the inflammatory process and joint damage in patients with rheumatoid arthritis.
To investigate the role of T cell responses to type II collagen (CII) in disease progression in patients with rheumatoid arthritis (RA). T cell proliferative responses to bovine CII by peripheral blood mononuclear cells (PBMC) from patients with early RA (duration < 5 yrs) were assayed by mixed lymphocyte culture. Clinical and laboratory variables including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were examined at the time of sampling. Radiographic damage on hand radiographs was evaluated by the method of Steinbrocker and Sharp. In a cross sectional study, patients (n = 22) with positive T cell responses (stimulation index 2) had higher levels of CRP and ESR than those (n = 21) not showing T cell responses. The number of damaged joints (by Steinbrocker's method) and damaged joint scores (by Sharp's method) were significantly higher in patients with positive T cell responses than in those without. The joint space narrowing scores correlated well with T cell responsiveness to CII. Patients (n = 15) with both positive T cell responses and RA-susceptible allotypes HLA-DR1 or DR4 had higher damaged joint scores than the remainder of the patients (n = 24). T cell proliferative responses to CII are associated with inflammatory activity and radiographic severity in RA. RA-susceptible allotypes positively relate to the radiographic progression associated with T cell responses to CII. Our data suggest that CII-reactive T cells may play a role in the pathogenic process of joint damage, especially in genetically susceptible patients.


Bi-Institutional Comparison of Robot-Assisted Laparoscopic Versus Open Ureteroureterostomy in the Pediatric Population.
Ureteroureterostomy (UU) is a useful surgical option for the management of duplication anomalies as well as obstructed single system ureters for children. We aimed to evaluate the safety, efficacy, and outcomes of robot-assisted laparoscopic UU (RALUU) compared with open UU (OUU) in the pediatric population. A retrospective review was performed at two institutions including six surgeons' experience with all cases of RALUU and OUU from January 2005 to June 2014. Indications for a surgical procedure included duplex systems with an upper pole ectopic ureter, obstructed ureterocele or lower pole vesicoureteral reflux, and obstruction in a single system. Transureteroureterostomy, laparoscopic UU, and major reconstruction cases where UU was the secondary procedure were excluded. There were 25 RALUU and 19 OUU cases included. All cases involved duplex systems except two proximal to distal anastomoses in single system obstructed kidneys. RALUUs were more likely to be performed proximally (P = 0.01) and with the use of cystoscopy and stent placement (P = <0.0001). Operative times and estimated blood loss were similar between the two groups. Postoperative complications included four febrile urinary tract infections in each group, one recurrence of nonfebrile urinary tract infection in the open group, and one postoperative obstruction at the ureterovesical junction because of attempted stent placement necessitating nephrostomy tube placement in the open group. This OUU patient was the only one to demonstrate more severe hydronephrosis after surgery on initial follow-up imaging that was again unrelated to the open UU procedure. RALUU had shorter hospital stays by 0.5 days (P = 0.04). Robot-assisted laparoscopic UU is a safe and effective alternative to open UU in children with duplication anomalies and single system obstructed ureters. Operative times and complication rates were comparable with slightly shorter length of hospitalization in robotic cases.


Nanomedicine: a new frontier in cancer therapeutics.
Nanotechnology is a cutting edge and rapidly evolving technology in medicine. The potential of nanomedicine in cancer therapy is infinitely promising due to the fact that novel developments are constantly being explored. This is particularly the case in the use of nanoparticles in both tumor diagnosis, as well as treatment. This article will attempt to describe some recent advances using nanoparticle drug delivery system in cancer therapy. The evolution history, the challenges and the role of nanoparticles in cancer drug delivery will briefly be discussed together with additional opportunities in cancer therapy. An overall understanding of these issues will help with further advancement of designing better drug delivery system that can be applied clinically.


The impact of co-located NHS walk-in centres on emergency departments.
To determine the impact of establishing walk-in centres alongside emergency departments (EDs) on attendance rates, visit duration, process, costs and outcome of care. Eight hospitals with co-located EDs and walk-in centres were compared with eight matched EDs without walk-in centres. Site visits were conducted. Routine data about attendance numbers and use of resources were analysed. A random sample of records of patients attending before and after the opening of walk-in centres was also assessed. Patients who had not been admitted to hospital were sent a postal questionnaire. At most sites, the walk-in centres did not have a distinct identity and there were few differences in the way services were provided compared with control sites. Overall, there was no evidence of an increase in attendance at sites with walk-in centres, but considerable variability across sites was found. The proportion of patients managed within the 4 h National Health Service target improved at sites both with and without walk-in centres. There was no evidence of any difference in reconsultation rates, costs of care or patient outcomes at sites with or without walk-in centres. Most hospitals in this study implemented the walk-in centre concept to a very limited extent. Consequently, there was no evidence of any effect on attendance rates, process, costs or outcome of care.


Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?
Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women. In view of the well-documented noxious effects repeatedly observed after anabolic steroid misuse, the confirmation and implementation of technically proven procedures for reporting norsteroid abuse in sports seems an important enough goal to protect athlete's health against such abuses and justifies up dating the review of the patent scientific and medical experience and knowledge gained over the last 50 years on nandrolone and its minor production in man and woman.


Mini-open anterior spine surgery for anterior lumbar diseases.
Minimally invasive surgeries including endoscopic surgery and mini-open surgery are current trend of spine surgery, and its main advantages are shorter recovery time and cosmetic benefits, etc. However, mini-open surgery is easier and less technique demanding than endoscopic surgery. Besides, anterior spinal fusion is better than posterior spinal fusion while considering the physiological loading, back muscle function, etc. Therefore, we aimed to introduce the modified "mini-open anterior spine surgery" (MOASS) and to evaluate the feasibility, effectiveness and safety in the treatment of various anterior lumbar diseases with this technique. A total of 61 consecutive patients (46 female, 15 male; mean age 58.2 years) from 1997 to 2004 were included in this study, with an average follow-up of 24-52 (mean 43) months. The disease entities included vertebral fracture (20), failed back surgery (13), segmental instability or spondylolisthesis (10), infection (8), herniated disc (5), undetermined lesion for biopsy (4), and hemivertebra (1). Lesions involved 13 cases at T12-L1, 18 at L1-L2, 18 at L2-L3, 22 at L3-L4 and 11 at L4-L5 levels. All patients received a single stage anterior-only procedure for their anterior lumbar disease. We used the subjective clinical results, Oswestry disability index, fusion rate, and complications to evaluate our clinical outcome. Most patients (91.8%) were subjectively satisfied with the surgery and had good-to-excellent outcomes. Mean operation time was 85 (62-124) minutes, and mean blood loss was 136 (minimal-250) ml in the past 6 years. Hospital stay ranged from 4-26 (mean 10.6) days. Nearly all cases had improved back pain (87%), physical function (90%) and life quality (85%). Most cases (95%) achieved solid or probable solid bony fusion. There were no major complications. Therefore, MOASS is feasible, effective and safe for patients with various anterior lumbar diseases.


Gluconate metabolism is required for virulence of the soft-rot pathogen Pectobacterium carotovorum.
Pectobacterium carotovorum is a ubiquitous soft rot pathogen that uses global virulence regulators to coordinate pathogenesis in response to undefined environmental conditions. We characterize an operon in P. carotovorum required for gluconate metabolism and virulence. The operon contains four genes that are highly conserved among proteobacteria (initially annotated ygbJKLM), one of which was misassigned as a type III secreted effector, (ygbK, originally known as hopAN1). A mutant with a deletion-insertion within this operon is unable to metabolize gluconate, a precursor for the pentose phosphate pathway. The mutant exhibits attenuated growth on the leaves of its host of isolation, potato, and those of Arabidopsis thaliana. Notably, the mutant hypermacerates potato tubers and is deficient in motility. Global virulence regulators that are responsive to cell wall pectin breakdown products and other undefined environmental signals, KdgR and FlhD, respectively, are misregulated in the mutant. The alteration of virulence mediated via changes in transcription of known global virulence regulators in our ygbJ-M operon mutant suggests a role for host-derived catabolic intermediates in P. carotovorum pathogenesis. Thus, we rename this operon in P. carotovorum vguABCD for virulence and gluconate metabolism.


Water-soluble, luminescent iridium(III)-ytterbium(III) complexes using dipyrido[3,2-a:2',3'-c]phenazine derivatives as bridging units.
Amino-substituted dipyrido[3,2-a:2',3'-c]phenazine (L(1)) and dimethyl-dipyrido[3,2-a:2',3'-c]phenazine (L(2)) have been investigated as: (i) chromophores in cyclen-based ligands for lanthanide(III) ions; (II) ancillary co-ligands in cyclometalated iridium(III) complexes; (III) bridging, linker units in covalently linked, water-soluble bimetallic lanthanide(III) iridium(III) hybrid complexes. The dipyrido[3,2-a:2',3'-c]phenazine (dppz) derivatives can act as sensitising chromophores (λ(ex) 400 nm) for Yb(III), resulting in characteristic near-IR emission at 950-1050 nm. The incorporation of dppz-type ligands into cyclometalated Ir(III) complexes of the general type [Ir(epqc)(2)(L(n))](PF(6)) (where epqc = ethylphenylquinoline carboxylate) gave luminescent species with solvent-sensitive emission properties. Steady state and time-resolved luminescence measurements on the water-soluble d-f hybrid species showed that Yb(III) can be sensitised using visible light.


Catalysis in the crystal: synchrotron radiation studies with glycogen phosphorylase b.
Direct observation of the progress of a catalysed reaction in crystals of glycogen phosphorylase b has been made possible through fast crystallographic data collection achieved at the Synchrotron Radiation source at Daresbury, UK. In the best experiments, data to 2.7 A resolution (some 108,300 measurements; 21,200 unique reflections) were measured in 25 min. In a series of time-resolved studies in which the control properties of the enzyme were exploited in order to slow down the reaction, the conversion of heptenitol to heptulose-2-phosphate, the phosphorylysis of maltoheptaose to yield glucose-1-phosphate and the oligosaccharide synthesis reaction involving maltotriose and glucose-1-phosphate have been monitored in the crystal. Changes in electron density in the difference Fourier maps are observed as the reaction proceeds not only at the catalytic site but also the allosteric and glycogen storage sites. Phosphorylase b is present in the crystals in the T state and under these conditions exhibits low affinity for both phosphate and oligosaccharide substrates. There are pronounced conformational changes associated with the formation and binding of the high-affinity dead-end product, heptulose-2-phosphate, which show that movement of an arginine residue, Arg 569, is critical for formation of the substrate-phosphate recognition site. The results are discussed with reference to proposals for the enzymic mechanism of phosphorylase. The feasibility for time-resolved studies on other systems and recent advances in this area utilizing Laue diffraction are also discussed.


Evaluation of reducibility of trunk asymmetry in lateral bending.
The value of the lateral bending test is important in the assessment of spinal curve mobility and prediction of surgical outcome in the treatment of adolescent idiopathic scoliosis (AIS). However, radiographic bending tests are unable to assess the reducibility of trunk asymmetry. This study aims to exploit surface topography measurement in order to evaluate the changes in shape of the trunk (a) between bending and neutral standing positions, and (b) between standing pre- and post-operative visits, in a cohort of adolescents with AIS having undergone surgical correction; and to correlate the differences measured in cases (a) and (b). Our cohort includes 13 patients with right thoracic AIS. Each patient had their 3D trunk surface digitized with a multi-head InSpeck system in standing posture (at the pre-op and post-op visits) and in maximum voluntary right and left bending (at the pre-op visit). We developed a novel trunk shape analysis method which produces a set of inclined trunk cross-sections allowing comparison between different postures. Two asymmetry indices, trunk rotation (TR) and back surface rotation (BSR), were computed in all cases and a statistical analysis was performed. Our correlation study (Pearson test) showed fair correlations in most cases between the changes in side-bending and those post-surgery, with the strongest relationship (p-value < 0.01) when combining the TR measurements from both bendings. These results provide evidence that the bending test can be used to assess trunk asymmetry reducibility. The proposed approach could provide a non-invasive trunk asymmetry reducibility test for routine clinical use in AIS surgery planning.


Recognition and polymorphism in host-parasite genetics.
Genetic specificity occurs in many host-parasite systems. Each host can recognize and resist only a subset of parasites; each parasite can grow only on particular hosts. Biochemical recognition systems determine which matching host and parasite genotypes result in resistance or disease. Recognition systems are often associated with widespread genetic polymorphism in the host and parasite populations. I describe four systems with matching host-parasite polymorphisms: plant-pathogen interactions, nuclear-cytoplasmic conflict in plants, restriction enzymes in bacterial defence against viruses, and bacterial plasmids that compete by toxin production and toxin immunity. These systems highlight several inductive problems. For example, the observed patterns of resistance and susceptibility between samples of hosts and parasites are often used to study polymorphism. The detectable polymorphism by this method may be a poor guide to the actual polymorphism and to the underlying biochemistry of host-parasite recognition. The problem of using detectable polymorphism to infer the true nature of recognition and polymorphism is exacerbated by non-equilibrium fluctuations in allele frequencies that commonly occur in host-parasite systems. Another problem is that different matching systems may lead either to low frequencies of host resistance and common parasites, or to common resistance and rare parasites. Thus low levels of host resistance or rare parasites do not imply that parasitism is an unimportant evolutionary force on host diversity. Knowledge of biochemical recognition systems and dynamical analysis of models provide a framework for analysing the widespread polymorphisms in host-parasite genetics.


Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies.
Antibody-dependent complement-mediated muscle fiber injury is a hypothetical immune effector response in inflammatory muscle diseases. Moreover, a sarcolemmal alteration in muscular dystrophies might trigger antibody-independent activation of the alternative complement pathway. We therefore searched for C5b9 complement membrane attack complex (MAC), immunoglobulin (Ig)G, and IgM deposits on nonnecrotic muscle fibers in muscle specimens from 81 patients with inflammatory myopathies, 45 patients with muscular dystrophies, and 19 patients with necrotizing myopathies. Sarcolemmal MAC deposits were present on nonnecrotic fibers (C+ fibers) in only two unusual types of inflammatory myopathy. By contrast, seven of 17 facioscapulohumeral dystrophy, four of nine limb-girdle dystrophy, and three of six merosin (laminin-alpha-2)-positive congenital muscular dystrophy but none of the Becker or Duchenne dystrophy specimens harbored C+ fibers. None of the C+ fibers immunostained for IgG or IgM, and none failed to immunostain for CD59 or CD46-inhibitors of the complement cascade. Our findings do not support a role for antibody-dependent complement-mediated muscle fiber injury in the major inflammatory muscle diseases. The cause and pathogenetic significance of the C+ fibers in the different types of muscular dystrophies remains to be elucidated.


Whole-cell bacterial bioreporter for actively searching and sensing of alkanes and oil spills.
Acinetobacter baylyi ADP1 was found to tolerate seawater and have a special ability of adhering to an oil-water interface of 10-80 µm emulsified mineral and crude oil droplets. These properties make ADP1 an ideal bacterial chassis for constructing bioreporters that are able to actively search and sense oil spill in water and soils. Acinetobacter baylyi bioreporter ADPWH_alk was developed and applied to the detection of alkanes and alkenes in water, seawater and soils. Bioreporter ADPWH_alk was able to detect a broad range of alkanes and alkenes with carbon chain length from C7 to C36. So far, ADPWH_alk is the only bioreporter that is able to detect alkane with carbon chain length greater than C18. This bioreporter responded to the alkanes in about 30 min and it was independent to the cell growth phase because of two point mutations in alkM promoter recognized by alkane regulatory protein ALKR. ADPWH_alk was applied to detect mineral oil, Brent, Chestnut and Sirri crude oils in water and seawater in the range 0.1-100 mg l(-1), showing that the bioreporter oil detection was semi-quantitative. This study demonstrates that ADPWH_alk is a rapid, sensitive and semi-quantitative bioreporter that can be useful for environmental monitoring and assessment of oil spills in seawater and soils.


DNA fingerprints of Mycobacterium tuberculosis do not change during the development of rifampicin resistance.
Drug-resistant tuberculosis has become a major public health problem. Resistance to rifampicin probably arises through mutations in the mycobacterial RNA polymerase. Patients may acquire rifampicin resistant tuberculosis by three mechanisms: (1) infection with a resistant organism, (2) selection of a sub-population of resistant organisms that remain contained whilst the more virulent wild type is present, (3) mutations within the population of bacilli causing the original infection. Sequential isolates of Mycobacterium tuberculosis were collected from 2 patients who developed rifampicin resistance whilst on treatment. One patient was immunosuppressed with HIV-infection; in the other patient the original isolate was also resistant to isoniazid. DNA fingerprinting techniques were used to type the isolates. No differences were found between the fingerprints of isolates from before and after the development of resistance. These data suggest that the third of the mechanisms listed above was responsible for the acquisition of rifampicin resistance in these 2 patients.


Impact of functional impairment in ankylosing spondylitis: impairment, activity limitation, and participation restrictions.
To describe difficulties in everyday activities related to impaired function in patients with ankylosing spondylitis (AS), and to examine possible sex differences in the impact of the disease. In addition, to examine the relationships between measures of personal characteristics, impairment, and activity/participation levels within the framework of the International Classification of Functioning (ICF). A total of 152 patients with AS took part in a clinical examination including anthropometric measures, blood samples, and self-reported disease related measures. The Canadian Occupational Performance Measure (COPM) interviews were performed to describe and measure activity limitations and participation restrictions perceived by the patient during the last year. The study variables were categorized and analyzed according to the levels of the ICF model using bivariate and multivariate statistical approaches. The mean age of patients was 47 (SD 13) years, 58% were men, and the mean disease duration was 15 (SD 12) years. The problems most frequently reported in COPM interviews were "interrupted sleeping," "turn head when driving," "carry groceries," and ""having energy for social activities." Women reported higher level of disease activity and more physical limitations than men. Disease activity and reduced mobility (impairment variables) seemed to result in more activity/participation restrictions in female than in male patients. The impairment variables explained only one-third of the activity and participation restrictions perceived by patients. Activity limitations and participation restrictions reported by patients were only partly explained by the impairment variables. Further research should identify social, structural, and attitudinal barriers influencing activity and participation in patients with AS.


Modulation of thin filament activation by breakdown or isoform switching of thin filament proteins: physiological and pathological implications.
In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning.


Changes in catastrophic health expenditure in post-conflict Sierra Leone: an Oaxaca-blinder decomposition analysis.
At the end of the eleven-year conflict in Sierra Leone, a wide range of policies were implemented to address both demand- and supply-side constraints within the healthcare system, which had collapsed during the conflict. This study examines the extent to which households' exposure to financial risks associated with seeking healthcare evolved in post-conflict Sierra Leone. This study uses the 2003 and 2011 cross-sections of the Sierra Leone Integrated Household Survey to examine changes in catastrophic health expenditure between 2003 and 2011. An Oaxaca-Blinder decomposition approach is used to quantify the extent to which changes in catastrophic health expenditure are attributable to changes in the distribution of determinants (distributional effect) and to changes in the impact of these determinants on the probability of incurring catastrophic health expenditure (coefficient effect). The incidence of catastrophic health expenditure decreased significantly by 18% from approximately 50% in 2003 t0 32% in 2011. The decomposition analysis shows that this decrease represents net effects attributable to the distributional and coefficient effects of three determinants of catastrophic health expenditure - ill-health, the region in which households reside and the type of health facility used. A decrease in the incidence of ill-health and changes in the regional location of households contributed to a decrease in catastrophic health expenditure. The distributional effect of health facility types observed as an increase in the use of public health facilities, and a decrease in the use of services in facilities owned by non-governmental organizations (NGOs) also contributed to a decrease in the incidence of catastrophic health expenditure. However, the coefficient effect of public health facilities and NGO-owned facilities suggests that substantial exposure to financial risk remained for households utilizing both types of health facilities in 2011. The findings support the need to continue expanding current demand-side policies in Sierra Leone to reduce the financial risk of exposure to ill health.


Intuitive web-based experimental design for high-throughput biomedical data.
Big data bioinformatics aims at drawing biological conclusions from huge and complex biological datasets. Added value from the analysis of big data, however, is only possible if the data is accompanied by accurate metadata annotation. Particularly in high-throughput experiments intelligent approaches are needed to keep track of the experimental design, including the conditions that are studied as well as information that might be interesting for failure analysis or further experiments in the future. In addition to the management of this information, means for an integrated design and interfaces for structured data annotation are urgently needed by researchers. Here, we propose a factor-based experimental design approach that enables scientists to easily create large-scale experiments with the help of a web-based system. We present a novel implementation of a web-based interface allowing the collection of arbitrary metadata. To exchange and edit information we provide a spreadsheet-based, humanly readable format. Subsequently, sample sheets with identifiers and metainformation for data generation facilities can be created. Data files created after measurement of the samples can be uploaded to a datastore, where they are automatically linked to the previously created experimental design model.


A pilot study about the oncologic safety of colonic self-expandable metal stents (SEMS) in obstructive colon cancer: is occlusion always better than "silent" perforation?
To evaluate the oncologic safety of colonic self-expandable metal stents (SEMS) in obstructive colon cancer. We retrospectively reviewed all the patients who were treated with endoscopic placement of a self-expandable metallic stent (SEMS) at our institution. A total of 26 patients were identified during the study period, of which 24 patients (92.30%) were treated with SEMS as a bridge-to-surgery and 2 (7.69%) as palliation. In 22 cases (80.76%), the stenosis was localized to the left side. Clinical success with resolution of bowel obstructions was achieved in 22 (84.61%) patients within a short period of time. Among patients treated successfully with SEMS insertion as bridge to surgery (n = 22), 20 (90.9%) underwent one-stage surgery with primary anastomosis while 2 patients (9.09%) underwent colostomy due to intraoperative evidence of a covered perforation by cancer tissue in the pelvis. Patients with subclinical perforation developed an early peritoneal carcinomatosis, 10 patients treated with curative intent subsequently developed liver metastasis after 24 months. We reported an overall poor outcome among patients treated with the insertion of SEMS. This led us to think that, in some cases, occlusion may be better than a "silent" perforation.


Prevalence of genotype-specific human papillomavirus in cytology specimens and cervical biopsies, and its implication in cervical cancer risk stratification: a retrospective study of 10647 cases.
Objective: This study aimed to describe the risk stratification of squamous cell carcinoma (SCC) and its precursor lesions based on HPV E6/E7 mRNA genotyping. Methods: 10647 hrHPV+ women (mean age 40.8 years), who had concurrent cytology and follow-up biopsy results available between September 2016 and May 2020, met the inclusion criteria and were selected for immediate risk analysis. Results: In this cohort, HPV-16 or 18/45+ women had significantly higher immediate risk of cervical cancer and precancer compared with other genotypes+ women. The relative immediate risk (RIR) of ASC-H+ was 2.0 (95% CI: 1.9-2.4) and SCC was 9.4 (95% CI: 5.5-15.6) for HPV-16 or 18/45+ women when compared with women positive for other 11 genotypes. Among follow-up biopsy cases, the RIR of CIN2+ was 2.7 (95% CI: 3.0-3.7) and SCC was 10.8 (95% CI: 7.2-17.4) for HPV-16 or 18/45+ women than women positive for other genotypes. Similarly, when compared with women positive for other genotypes, the RIR of CIN2+ was 2.9 (95% CI: 2.7-4.6) and SCC was 13.8 (95% CI: 3.0-66.2) for HPV-16 or 18/45+ women with ASC-US, and RIR of CIN2+ was 3.3 (95% CI: 3.1-4.6) and SCC was 22.3 (95% CI: 2.8-176.8) for HPV-16 or 18/45+ women with NILM. Conclusions: This study supports that hrHPV mRNA genotyping can be an effective risk stratification tool to identify individual at higher risk for cervical cancer or precancer, and provides important evidences for the future modifications for current China cervical cancer screening guidelines.