Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register

Objective. Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK. This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a national prospective observational register. Methods. The British Society for Rheumatology Biologics Register (BSRBR) recruited patients starting anti-TNF therapy for AS between 2002 and 2006. Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months. Covariates included age, gender, disease duration, baseline BASDAI and BASFI, presence of raised inflammatory markers (defined as twice the upper limit of normal) and DMARD therapy. Results. The cohort was young (median age 43 years) and 82% were males. Median baseline BASDAI was 7.6 and BASFI 7.9. At 6 months, the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U, respectively; 52% reached a BASDAI50. Patients with raised inflammatory markers at the start of therapy had a 0.9-U (95% CI 0.2, 1.5) better improvement in BASDAI compared with those without. Lesser responses were seen in those with higher baseline BASFI scores. Women had a 1.1-U (95% CI 0.3, 2.0) greater improvement in BASFI at 6 months, as did those who were receiving concurrent DMARD therapy [0.9 U (95% CI 0.2, 1.7)]. Conclusions. The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity. Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI, identifying a group of patients who may be more responsive to anti-TNF therapies, although the results were not confined to this group.
The orlA gene from Aspergillus nidulans encodes a trehalose‐6‐phosphate phosphatase necessary for normal growth and chitin synthesis at elevated temperatures

A cosmid carrying the orIA gene from Aspergillus nidulans was identified by complementation of an orlA1 mutant strain with DNA from the pKBY2 cosmid library. An orlA1 complementing fragment from the cosmid was sequenced. orlA encodes a predicted polypeptide of 227 amino acids (26 360 Da) that is homologous to a 211‐amino‐acid domain from the polypeptide encoded by the Saccharomyces cerevisiae TPS2 gene and to almost the entire Escherichia coli of otsB‐encoded polypeptide. TPS2 and otsB each specify a trehalose‐6‐phosphate phosphatase, an enzyme that is necessary for trehalose synthesis. orlA disruptants accumulate trehalose‐6‐phosphate and have reduced trehalose‐6‐phosphatate phosphatase levels, indicating that the gene encodes a tre‐halose‐6‐phosphatate phosphatase. Disruptants have a nearly‐wild‐type morphology at 32°C. When germinated at 42°C, the conidia and hyphae from disruptants are chitin deficient, swell excessively, and lyse. The lysis is almost completely remedied by osmotic stabilizers and is partially remedied by N‐acetylglucosamine (GlcNAc). The activity of glutamine:fructose‐6‐phosphate amido‐transferase (GFAT), the first enzyme unique to aminosugar synthesis, is reduced and is labile in orIA disruption strains. The findings are consistent with the hypothesis that trehalose‐6‐phosphate reduces the temperature stability of GFAT and other enzymes of chitin metabolism at elevated temperatures. The results extend to filamentous organisms the observation that mutations in fungal trehalose synthesis are highly pleiotropic and affect aspects of carbohydrate metabolism that are not directly related to trehalose synthesis.
Health and Quality of Life Outcomes

Background: It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL). However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of selfreported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences. Methods: In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13–21 years old (response rate 97%). Results: Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/ wheezing, eczema/rash, rhino-conjunctivitis). A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p < 0.001). The adolescents with allergy-like conditions reported significantly lower HRQL (p < 0.001) in seven of the eight SF-36 health scales compared with adolescents without such conditions, regardless of whether the condition had been doctor-diagnosed or not. Most adolescents suffered from complex allergy-like conditions. Conclusions: The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools. Published: 19 November 2004 Health and Quality of Life Outcomes 2004, 2:65 doi:10.1186/1477-7525-2-65 Received: 28 September 2004 Accepted: 19 November 2004 This article is available from: http://www.hqlo. com/content/2/1/65 © 2004 Marklund et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prevalence of radiographic parameters predisposing to femoroacetabular impingement in young asymptomatic Chinese and white subjects.

BACKGROUND Osteoarthritis of the hip is five to ten times more common in white people than in Chinese people. Little is known about the true prevalence of femoroacetabular impingement or its role in the development of osteoarthritis in the Chinese population. A cross-sectional study of both white and Chinese asymptomatic individuals was conducted to compare the prevalences of radiographic features posing a risk for femoroacetabular impingement in the two groups. It was hypothesized that that there would be proportional differences in hip anatomy between the white and Asian populations. METHODS Pelvic computed tomography scans of 201 subjects (ninety-nine white Belgians and 102 Chinese; 105 men and ninety-six women) without hip pain who were eighteen to forty years of age were assessed. The original axial images were reformatted to three-dimensional pelvic models simulating standardized radiographic views. Ten radiographic parameters predisposing to femoroacetabular impingement were measured: alpha angle, anterior offset ratio, and caput-collum-diaphyseal angle on the femoral side and crossover sign, ischial spine projection, acetabular anteversion angle, center-edge angle, acetabular angle of Sharp, Tönnis angle, and anterior acetabular head index on the acetabular side. RESULTS The white subjects had a less spherical femoral head than the Chinese subjects (average alpha angle, 56° compared with 50°; p<0.001). The Chinese subjects had less lateral acetabular coverage than the white subjects, with average center-edge angles of 35° and 39° (p<0.001) and acetabular angles of Sharp of 38° and 36° (p<0.001), respectively. A shallower acetabular configuration was predominantly present in Chinese women. CONCLUSIONS Significant differences in hip anatomy were demonstrated between young asymptomatic Chinese and white subjects. However, the absolute size of the observed differences appears to contrast with the reported low prevalence of femoroacetabular impingement in Chinese individuals compared with the high prevalence in white populations.
FIRE: flexible Intra-AS routing environment

Current routing protocols are monolithic, specifying the algorithm used to construct forwarding tables, the metric used by the algorithm (generally some form of hop-count), and the protocol used to distribute these metrics as an integrated package. The Flexible Intra-AS Routing Environment (FIRE) is a link-state, intra-domain routing protocol that decouples these components. FIRE supports run-time-pro- grammable algorithms and metrics over a secure link-state distribution protocol. By allowing the network operator to dynamically reprogram both the information being advertised and the routing algorithm used to construct forwarding tables in Java, FIRE enables the development and deployment of novel routing algorithms without the need for a new protocol to distribute state. FIRE supports multiple concurrent routing algorithms and metrics, each constructing separate forwarding tables. By using operator-specified packet filters, separate classes of traffic are routed using completely different routing algorithms, all supported by a single routing protocol.
Effects of tetracaine on sarcoplasmic calcium release in mammalian skeletal muscle fibres

1 Single muscle fibres were dissociated enzymatically from the extensor digitorum communis muscle of rats. The fibres were mounted into a double Vaseline gap experimental chamber and the events in excitation‐contraction coupling were studied under voltage clamp conditions in the presence and absence of the local anaesthetic tetracaine. 2 Changes in intracellular calcium concentration ([Ca2+]i) were monitored using the calcium sensitive dyes antipyrylazo III and fura‐2 and the rate of calcium release (Rrel) from the sarcoplasmic reticulum (SR) was calculated. Tetracaine decreased the maximal attained [Ca2+]i and suppressed, in a dose‐dependent manner, both the early peak and the steady level of Rrel in the voltage range examined. 3 The concentration dependence of the effects on the two kinetic components of Rrel were almost identical with a half‐effective concentration (K50) of 70 and 71 μm and a Hill coefficient (nH) of 2.7 and 2.3 for the peak and the steady level, respectively. Furthermore, the drug did not alter the peak to steady level ratio up to a concentration (50 μm) that caused a 35 ± 5% reduction in calcium release. Higher concentrations did suppress the ratio but the degree of suppression was voltage independent. 4 Tetracaine (50 μm) neither influenced the total available intramembrane charge nor altered its membrane potential dependence. It shifted the transfer function, the normalized SR permeability versus normalized charge to the right, indicating that similar charge transfer caused a smaller increase in SR permeability. 5 To explore the site of action of tetracaine further the ryanodine receptor (RyR) calcium release channel of the SR was purified and reconstituted into planar lipid bilayers. The reconstituted channel had a conductance of 511 ± 14 pS (n= 8) in symmetric 250 mm KCl that was not affected by tetracaine. Tetracaine decreased the open probability of the channel in a concentration‐dependent manner with K50= 68 μm and nH= 1.5. 6 These experiments show that tetracaine suppresses SR calcium release in enzymatic isolated mammalian skeletal muscle fibres. This effect is due, presumably, to the decreased open probability of the RyR in the presence of the drug. Since both the inactivating peak and the steady level of Rrel were equally affected by tetracaine, our observations suggest that there is a tight coupling between these kinetic components of SR calcium release in mammalian skeletal muscle.
Opportunistic web access via WLAN hotspots

Mobile phones are becoming commonplace for consuming Internet content and services. However, availability, affordability, and quality of the supposedly ubiquitous cellular network infrastructure may be limited, so that delay-tolerant web access via WLAN hotspots becomes an interesting alternative, even in urban areas. In this paper we explore mobile web access using asynchronous messaging via WLAN hotspots: for nodes directly connected to an access point and nodes relying on others for message forwarding. We investigate different routing and caching approaches using real-world access point locations in Helsinki. We find that a significant number of requests can be satisfied without requiring an always-on infrastructure, provided that users are willing to tolerate some response delay; this allows offloading traffic from the cellular network. We also report on our prototype implementation of mobile DTN-based web browsing.
Adoptive T-cell therapy for malignant disorders

Adoptive cell transfer using ex vivo manipulated T lymphocytes has emerged as an important advance in cancer immunotherapy, allowing for re-education and re-setting of the host immune system. In this perspective article, Drs. Powell and Levine discuss the current situation in this field. See related paper on page 1523.
Importance of motivation for learning

Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online's data policy on reuse of materials please consult the policies page. 47 courses at various faculties of the Open University in Israel and found that the majority (80%) of students contributed only a small amount (20%) of messages. But not only differences in the amount of contributions by students have been found. For example, De Laat and Lally (2003) showed that students in an online E-learning Master's programme also differed with respect to the type (cognitive, affective, metacognitive) of contributions. In a Bachelor's freshman course of educational science, Schellens and Valcke (2005) found significant differences with respect to both amount and type (social, cognitive) of discourse. Although recent research findings indicate that learners differ with respect to the amount and type of discourse contributed, little is known about what the causes of these differences are. Within the field of Computer-Supported Collaborative Learning, researchers try to understand what the underlying reasons for a lack of contributions to cognitive discourse are and how to solve them. For example, Lowry and colleagues (2006) found that informatics learners who in an experimental design collaborated in class and were complemented with ICT established higher levels of communication quality than learners who collaborated only virtually. Hurme and colleagues (2007) analysed the interaction patterns among secondary school children who worked online in pairs on mathematical problems. Metacognitive activity varied among participants, which subsequently influenced the interaction among pairs of learners. Furthermore, by using Social Network Analysis 2 some pairs became central contributors to discourse, while others were less active and were positioned on the outer fringe of the social network (Hurme, Palonen, & Järvelä, 2007). Recently several researchers have investigated the role of motivation in CSCL. For example, by measuring goal-oriented motivation (Pintrich & De Groot, 1990), Yang and colleagues (2006) found evidence that motivation is positively related with how learners perceive each other's presence in online courses. Järvelä and colleagues (2008) found that students who were working together in groups of 3-5 students reported more (favourable) learning goals and fewer performance goals in the face-to-face setting than students in virtual groups. Besides goal-oriented motivation, several other factors might influence motivation like the degree of self-determination of learners (Ryan & Deci, 2000a, 2000b). For example, in an online setting learners …
Typology of Human-Wildlife Conflicts Encountered by the Local Communities in Kieni-West Sub-County, Kenya

Human-wildlife conflicts (HWC) have become more frequent and severe over recent decade as a result of human population growth, expansion of agricultural and industrial activities which together have led to increased human encroachment on uninhabited and areas meant for wild animals. This study focused on the typology of human-wildlife conflicts in Kieni West Sub-County, Kenya. This study used a descriptive survey design. The target population of the study was 2340 households drawn from three v i l l a g e s namely: Amboni, Bendeni and Njeng’u. Data was collected using questionnaires, interview schedules for key informants, participant observations and focus group discussions. Collected data was later analyzed using descriptive statistics in form of frequencies, percentages, chi-squared tests and spearman’s rank correlation coefficient. Different types of human-wildlife conflicts and their occurrences were analyzed by frequencies and percentages. Chi-squared test was used to compare different variables while Spearman rank correlation coefficient was used to establish the relationship between variables. Information given by key informants and opinions by local leaders was analyzed thematically. Data was presented by frequency tables, figures, percentages and texts in a descriptive way. The findings of this study showed that the local communities in Kieni County encountered with various types of human-wildlife conflicts including human injuries and threats (3%), crop damage (53%), livestock predation (23%), disease transmission to livestock (16%) and property damage (5%). The observed difference in types of humanwildlife conflicts was significant (X=248.7, df=5, P˂0.001).
People with dementia as peer workers, challenges, and benefits: a thematic analysis and nominal groups study

ABSTRACT Background: There are national initiatives to involve service users in service delivery. However, programs employing people with dementia as peer support workers (PSWs) in memory services are in their infancy. This study is the first to explore the challenges and benefits to staff and peers involved in such a program. Methods: Focus groups, structured based on nominal groups (NG) methodology were run with PSWs and clinical staff from two memory services. In total, there were 12 participants, with three focus groups: PSWs alone (n = 3); staff members alone (n = 6); and PSWs and staff members combined (n = 6). Data were analyzed through thematic analysis of recorded session content and the ranking of themes inherent in an NG approach. Results: Perceived benefits of the PSW program were similar for staff and PSWs and included personal benefits for PSWS and stereotype reduction for staff. More challenges were reported by staff than PSWs, but both groups agreed that role definition and dealing with the cognitive deterioration inherent in dementia were key issues. Conclusions: The PSW program does have benefits for involved staff and PSWs. However, the challenges identified highlight the need for careful and consensual setup and consideration of power dynamics, with agreed roles and clear guidelines to deal with cognitive deterioration.
Epidemiological study of acute poisoning in children: a 5-year retrospective study in the Paediatric University Hospital in Białystok, Poland

Background Poisoning among children and youths in the northeastern part of Poland accounted for 25% of the total number of patients admitted to the Hospital Emergency Department of the Paediatric University Hospital of Bialystok. We hypothesise that the epidemiology of poisoned paediatric patients admitted is related to increase in ‘designer drugs’ (mainly amphetamine- and ecstasy-like psychostimulants, hallucinogens and synthetic cannabinoids (‘spice’) intake, which became popular 5 years ago in our country. Methods A retrospective chart review of medical records of 489 patients admitted due to poisoning in the 5-year period (2006–2010). The data included: age, sex, place of residence, nature of the substance, causes of poisoning, former use of psychoactive stimulants, accompanying self-mutilation and injuries and length of hospitalisation. Categorical variables were expressed as percentages, and continuous variables as mean and SD. The data were collected in a Microsoft Excel database. Statistical analysis was performed using the Statistical Programme for Social Sciences. Results Out of 2176 hospitalised children, 489 were admitted because of poisoning. Out of these, 244 (49.9%) were hospitalised due to intoxication by alcohol. Only eight children used designer drugs. The mean age of all patients in our group was 12.86±5.04 years, of which 52.4% were male. Poisoning was intentional in 75.5%, and accidental in 24.5% of cases. Appearance of ‘designer drugs’ had no significant impact on the number and epidemiology of poisonings in our group.
Childhood Adversity and Adult Onset of Hypertension and Heart Disease in São Paulo, Brazil

Using data from the São Paulo Megacity Mental Health Survey and logistic regression models, we studied how childhood neglect, physical abuse, sexual abuse, and family violence were related to adult hypertension and heart disease. After adjustment for sociodemographic factors, child physical abuse was associated with hypertension and heart disease, whereas family violence was associated with hypertension. Efforts to curb child physical abuse could potentially reduce subsequent hypertension and heart disease.
Factors governing the protonation state of cysteines in proteins: an Ab initio/CDM study.

The detailed mechanism of metal-cysteine binding is still poorly understood. It is not clear if every metal cation can induce cysteine deprotonation, how the dielectric medium affects this process, and the extent to which other ligands from the metal's first and second coordination shell influence cysteine ionization. It is also not clear if the zinc cation, with its positive charge reduced by charge transfer from the first two bound cysteinates, could still assist deprotonation of the next one or two cysteines in Cys3His and Cys4 zinc-finger cores. Here, we elucidate the factors governing the cysteine protonation state in metal-binding sites, in particular in Zn.Cys4 complexes, using a combined ab initio and continuum dielectric approach. Transition metal dications such as Zn2+ and Cu2+ and trivalent cations such as Al3+ with pronounced ability to accept charge from negatively charged Cys- are predicted to induce cysteine deprotonation, but not "hard" divalent cations such as Mg2+. A high dielectric medium was found to favor cysteine deprotonation, while a low one favored the protonated state. Polarizable ligands in the metal's first shell that can competitively donate charge to the metal cation were found to lower the efficiency of the metal-assisted cysteine deprotonation. The calculations predict that the zinc cation could assist deprotonation of all the cysteines during the folding of Cys4 zinc-finger cores and the [Zn. (Cys-)4]2- state is likely to be preserved in the final folded conformation of the protein provided the binding site is tightly encapsulated by backbone peptide groups or lysine/arginine side chains, which stabilize the ionized cysteine core.