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Introdução: A pandemia trouxe inúmeros desafios aos serviços de saúde e isso não foi diferente nos serviços de hemoterapia. O novo cenário exigiu constantes modificações nas rotinas de trabalho de acordo com o que se descobria a respeito da doença e seus impactos na transfusão de sangue. Novas estratégias de captação de doadores, manejo ainda mais criterioso dos estoques de hemocomponentes e adequação da infraestrutura às medidas sanitárias são alguns exemplos das adaptações que ocorreram. Concomitantemente ocorreu uma importante alteração do perfil de pacientes atendidos nos hospitais em geral com redução significativa de pacientes cirúrgicos e elevação do número de atendimentos clínicos, em especial em ambientes de terapia intensiva. Objetivo: Avaliar o volume de transfusões por tipo de hemocomponente antes e depois do início do cenário de pandemia de COVID-19 em uma instituição privada da região sul da cidade de São Paulo. Métodos: Foi realizado estudo descritivo e comparativo através de análise de dados obtidos no sistema informatizado de gerenciamento da agência transfusional. Foram incluídos os dados referentes às transfusões que ocorreram no período abril/2019 a março/2021 classificando-as de acordo com o tipo de hemocomponente diferenciando-se entre componentes eritrocitários, componentes plaquetários e componentes plasmáticos (plasma e crioprecipitado). Resultados: Nos 12 meses que antecederam o início da pandemia foram realizadas 5.613 transfusões, sendo 2.553 concentrados de hemácias (45%), 1.407 concentrados de plaquetas (25%), 1.453 plasmas frescos congelados (26%) e 200 crioprecipitados (4%). Já no período de abril/2020 a março/2021, foram realizadas 6.091 transfusões, sendo 2.599 concentrados de hemácias (43%), 2.614 concentrados de plaquetas (43%), 598 plasmas frescos congelados (10%) e 280 crioprecipitado (4%). Observou-se que no período houve um crescimento do número total de transfusões de 8% em relação ao período pré pandemia, além de uma alteração do perfil de consumo dos hemocomponentes, com expressivo crescimento absoluto e relativo do número de transfusões de componentes plaquetários (25% versus 43%). Conclusões: A pandemia alterou significativamente o perfil de paciente atendido nos hospitais de todo o mundo e isso não foi diferente no hospital estudado. Os pacientes com quadros graves de COVID-19 apresentavam frequentemente quadros de insuficiência respiratória hipoxêmica com necessidade de circulação extracorpórea com membrana de oxigenação (ECMO) além distúrbios de coagulação o que resultou no aumento do consumo de concentrados de plaquetas.

The use of mobile phones has been identified as a potential way to bring the benefits of educational technology to a wider audience, including in low-connectivity settings. This is a topic that has received renewed interest recently as a result of the COVID-19 pandemic and school closures. While a number of recent studies have demonstrated good potential for mobile phones and SMS to be used to support learning, there are also questions about how equitable this medium is in practice. We conducted a telephone survey with learners (n = 122) and their caregivers (n = 124) who use M-Shule, an SMS-based educational platform in Kenya, in order to understand their attitudes towards mobile learning, and the benefits and constraints. In particular, we consider whether there are differences in responses according to gender and/or location, to shed light on whether use is equitable. We find that girls and boys face similar barriers to use, and the technology is perceived to be equally beneficial. We identify some areas for potential further support for all learners through mobile learning.

Parental feeding practices are linked to child disordered eating. Less research has examined these associations in young adult children, particularly college-aged, and studies examining relationships between parent feeding practices and mental health concerns are also limited. Examining these relationships in college students is important because higher education represents a period of marked development and maintenance of maladaptive eating behaviors and mental health concerns. A cross-sectional study with the inclusion of 64 parent-child (i.e., young adult) dyads examined relationships between retrospective parental feeding practices and current disordered eating and mental health concerns in their young adult children. Higher retrospective parental structured feeding practices were associated with lower young adult current disordered eating and mental health concerns. Collegiate health-promotion programs may consider college students' early food environments, particularly structured food environments, as factors that may be associated with adaptive eating behaviors and better mental health outcomes.

Abstract The blood–brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.

Purpose: Retinopathy of prematurity (ROP) is one of the leading causes of blindness in children. Although the role of oxygen in the pathophysiology of ROP is well established, a precise understanding of the dynamic relationship between oxygen exposure ROP incidence and severity is lacking. The purpose of this study was to evaluate the correlation between time-dependent oxygen variables and the onset of ROP. Design: Retrospective cohort study. Participants: Two hundred thirty infants who were born at a single academic center and met the inclusion criteria were included. Infants are mainly born between January 2011 and October 2022. Methods: Patient data were extracted from electronic health records (EHRs), with sufficient time-dependent oxygen data. Clinical outcomes for ROP were recorded as none/mild or moderate/severe (defined as type II or worse). Mixed-effects linear models were used to compare the 2 groups in terms of dynamic oxygen variables, such as daily average and the coefficient of variation (COV) fraction of inspired oxygen (FiO2). Support vector machine (SVM) and long-short-term memory (LSTM)-based multimodal models were trained with fivefold cross-validation to predict which infants would develop moderate/severe ROP. Gestational age (GA), birth weight, and time-dependent oxygen variables were used to develop predictive models. Main Outcome Measures: Model cross-validation performance was evaluated by computing the mean area under the receiver operating characteristic (AUROC) curve, precision, recall, and F1 score. Results: We found that both daily average and COV of FiO2 were associated with more severe ROP (adjusted P

This review paper describes the energy-upgraded Continuous Electron Beam Accelerator Facility (CEBAF) accelerator. This superconducting linac has achieved 12 GeV beam energy by adding 11 new high-performance cryomodules containing 88 superconducting cavities that have operated cw at an average accelerating gradient of 20 MV/m. After reviewing the attributes and performance of the previous 6 GeV CEBAF accelerator, we discuss the upgraded CEBAF accelerator system in detail with particular attention paid to the new beam acceleration systems. In addition to doubling the acceleration in each linac, the upgrade included improving the beam recirculation magnets, adding more helium cooling capacity to allow the newly installed modules to run cold, adding a new experimental hall, and improving numerous other accelerator components. We review several of the techniques deployed to operate and analyze the accelerator performance and document system operating experience and performance. In the final portion of the document, we present much of the current planning regarding projects to improve accelerator performance and enhance operating margins, and our plans for ensuring CEBAF operates reliably into the future. For the benefit of potential users of CEBAF, the performance and quality measures for the beam delivered to each of the experimental halls are summarized in the Appendix.

This study investigated the racial/ethnic differences in COVID-19-related worry amongst family caregivers of adults with intellectual and developmental disabilities (IDD) living in Texas using the COVID-Related Thoughts and Behavioral Symptoms-Adult Version (COV-TaBS-A) questionnaire. Two hundred and six caregivers completed the survey. Compared to White caregivers, Latino caregivers were more likely to be very concerned about having enough food and supplies (adj OR 3.41, 95% CI [1.50, 7.74]) when adjusting for being that sole caregiver and using provider services. In free text questions, caregivers described feeling overwhelmed by additional responsibilities, disruptions in home health services, and concerns about their loved ones' wellness. Study findings can be used to strategize support for caregivers of adults with IDD during pandemic/emergency situations. [ABSTRACT FROM AUTHOR]

This study tested the feasibility and initial efficacy of a cognitive-behavioral summer treatment (summerMAX[superscript yc]) for high-functioning young children, ages 4-6 years, with ASD (HFASD; without intellectual disability). The treatment was conducted 5 days per week, 6 h per day, over 5 weeks in the summer and included skills instruction and therapeutic activities targeting social/social-communication skills, facial-emotion recognition, and interest expansion. Skills instruction sessions and therapeutic activities utilized direct instruction, modeling, role-play, performance feedback, and repeated practice. A behavioral system was also implemented to increase skills development and reduce ASD symptoms and disruptive behaviors, and parents participated in weekly parent training. Feasibility was supported in high levels of treatment fidelity and child, parent, and staff clinician satisfaction, and there was no attrition or adverse events/responses. Results of the primary outcome measure (coding of the children's social performance by naïve raters) indicated that 10 of the 12 children were treatment responders (d = 1.76). Significant post-treatment improvements were also found on secondary measures (parent and staff clinician ratings) of social/social-communication skills and ASD symptoms, as well as a range of adaptive behaviors (effect sizes in the medium and large ranges). Results supported the feasibility of the treatment and suggested that it may yield positive outcomes for 4-6 year olds with HFASD. Recommendations for ongoing testing are provided.

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness related to oxygen exposure in premature infants. Since oxygen monitoring protocols have reduced the incidence of treatment-requiring ROP (TR-ROP), it remains unclear whether oxygen exposure remains a relevant risk factor for incident TR-ROP and aggressive ROP (A-ROP), a severe, rapidly progressing form of ROP. The purpose of this proof-of-concept study was to use electronic health record (EHR) data to evaluate early oxygen exposure as a predictive variable for developing TR-ROP and A-ROP. Design: Retrospective cohort study. Participants: Two hundred forty-four infants screened for ROP at a single academic center. Methods: For each infant, oxygen saturations and fraction of inspired oxygen (FiO2) were extracted manually from the EHR until 31 weeks postmenstrual age (PMA). Cumulative minimum, maximum, and mean oxygen saturation and FiO2 were calculated on a weekly basis. Random forest models were trained with 5-fold cross-validation using gestational age (GA) and cumulative minimum FiO2 at 30 weeks PMA to identify infants who developed TR-ROP. Secondary receiver operating characteristic (ROC) curve analysis of infants with or without A-ROP was performed without cross-validation because of small numbers. Main Outcome Measures: For each model, cross-validation performance for incident TR-ROP was assessed using area under the ROC curve (AUC) and area under the precision-recall curve (AUPRC) scores. For A-ROP, we calculated AUC and evaluated sensitivity and specificity at a high-sensitivity operating point. Results: Of the 244 infants included, 33 developed TR-ROP, of which 5 developed A-ROP. For incident TR-ROP, random forest models trained on GA plus cumulative minimum FiO2 (AUC = 0.93 ± 0.06; AUPRC = 0.76 ± 0.08) were not significantly better than models trained on GA alone (AUC = 0.92 ± 0.06 [P = 0.59]; AUPRC = 0.74 ± 0.12 [P = 0.32]). Models using oxygen alone showed an AUC of 0.80 ± 0.09. ROC analysis for A-ROP found an AUC of 0.92 (95% confidence interval, 0.87–0.96). Conclusions: Oxygen exposure can be extracted from the EHR and quantified as a risk factor for incident TR-ROP and A-ROP. Extracting quantifiable clinical features from the EHR may be useful for building risk models for multiple diseases and evaluating the complex relationships among oxygen exposure, ROP, and other sequelae of prematurity.

Cooling of hadron beams is critically important in the next generation of hadron storage rings for delivery of unprecedented performance. One such application is the electron-ion collider presently under development in the US. The desire to develop electron coolers for operation at much higher energies than previously achieved necessitates the use of radio-frequency (rf) fields for acceleration as opposed to the conventional, electrostatic approach. While electron cooling is a mature technology at low energy utilizing a dc beam, rf acceleration requires the cooling beam to be bunched, thus extending the parameter space to an unexplored territory. It is important to experimentally demonstrate the feasibility of cooling with electron bunches and further investigate how the relative time structure of the two beams affects the cooling properties; thus, a set of four pulsed-beam cooling experiments was carried out by a collaboration of Jefferson Lab and Institute of Modern Physics (IMP). The experiments have successfully demonstrated cooling with a beam of electron bunches in both the longitudinal and transverse directions for the first time. We have measured the effect of the electron bunch length and longitudinal ion focusing strength on the temporal evolution of the longitudinal and transverse ion beam profile and demonstrate that if the synchronization can be accurately maintained, the dynamics are not adversely affected by the change in time structure.

Deletions of chromosome 1p36 are associated with a high incidence of congenital heart defects (CHDs). The arginine-glutamic acid dipeptide repeats gene (RERE) is located in a critical region for CHD on chromosome 1p36 and encodes a cardiac-expressed nuclear receptor co-regulator. Mutations affecting RERE cause atrial and ventricular septal defects (VSDs) in humans, and RERE-deficient mice also develop VSDs. During cardiac development, mesenchymal cells destined to form part of the atrioventricular (AV) septum are generated when endocardial cells in the AV canal undergo epithelial-to-mesenchymal transition (EMT) and migrate into the space between the endocardium and the myocardium. These newly generated mesenchymal cells then proliferate to fill the developing AV endocardial cushions. Here, we demonstrate that RERE-deficient mouse embryos have reduced numbers of mesenchymal cells in their AV endocardial cushions owing to decreased levels of EMT and mesenchymal cell proliferation. In the endocardium, RERE colocalizes with GATA4, a transcription factor required for normal levels of EMT and mesenchymal cell proliferation. Using a combination of in vivo and in vitro studies, we show that Rere and Gata4 interact genetically in the development of CHDs, RERE positively regulates transcription from the Gata4 promoter and GATA4 levels are reduced in the AV canals of RERE-deficient embryos. Tissue-specific ablation of Rere in the endocardium leads to hypocellularity of the AV endocardial cushions, defective EMT and VSDs, but does not result in decreased GATA4 expression. We conclude that RERE functions in the AV canal to positively regulate the expression of GATA4, and that deficiency of RERE leads to the development of VSDs through its effects on EMT and mesenchymal cell proliferation. However, the cell-autonomous role of RERE in promoting EMT in the endocardium must be mediated by its effects on the expression of proteins other than GATA4. This article has an associated First Person interview with the first author of the paper.

The human genome hosts several active families of transposable elements (TEs), including the Alu, LINE-1, and SVA retrotransposons that are mobilized via reverse transcription of RNA intermediates. We evaluated how insertion polymorphisms generated by human retrotransposon activity may be related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS). To address this question, we performed a genome-wide screen for retrotransposon polymorphism disease associations that are linked to TE induced gene regulatory changes. Our screen first identified polymorphic retrotransposon insertions found in linkage disequilibrium (LD) with single nucleotide polymorphisms that were previously associated with common complex diseases by GWAS. We further narrowed this set of candidate disease associated retrotransposon polymorphisms by identifying insertions that are located within tissue-specific enhancer elements. We then performed expression quantitative trait loci analysis on the remaining set of candidates in order to identify polymorphic retrotransposon insertions that are associated with gene expression changes in B-cells of the human immune system. This progressive and stringent screen yielded a list of six retrotransposon insertions as the strongest candidates for TE polymorphisms that lead to disease via enhancer-mediated changes in gene regulation. For example, we found an SVA insertion within a cell-type specific enhancer located in the second intron of the B4GALT1 gene. B4GALT1 encodes a glycosyltransferase that functions in the glycosylation of the Immunoglobulin G (IgG) antibody in such a way as to convert its activity from pro- to anti-inflammatory. The disruption of the B4GALT1 enhancer by the SVA insertion is associated with down-regulation of the gene in B-cells, which would serve to keep the IgG molecule in a pro-inflammatory state. Consistent with this idea, the B4GALT1 enhancer SVA insertion is linked to a genomic region implicated by GWAS in both inflammatory conditions and autoimmune diseases, such as systemic lupus erythematosus and Crohn’s disease. We explore this example and the other cases uncovered by our genome-wide screen in an effort to illuminate how retrotransposon insertion polymorphisms can impact human health and disease by causing changes in gene expression.

Embrittlement threatens the useful lifetime of books, maps, manuscripts, and works of art on paper during storage, circulation, and display in libraries, museums, and archives. Past studies have traced much of the embrittlement to the Brønsted-acidic conditions under which printing papers have been made, especially during the period between the mid 1800s to about 1990. This article reviews measures that conservators and collection managers have taken to reduce the acidity of books and other paper-based materials, thereby decreasing the rates of acid-catalyzed hydrolysis and other changes leading to embrittlement. Technical challenges include the selection of an alkaline additive, selecting and implementing a way to distribute this alkaline substance uniformly in the sheet and bound volumes, avoiding excessively high pH conditions, minimizing the rate of loss of physical properties such as resistance to folding, and avoiding any conditions that cause evident damage to the documents one is trying to preserve. Developers have achieved considerable progress, and modern librarians and researchers have many procedures from which to choose as a starting point for further developments.

Intracellular labels such as dextran coated superparamagnetic iron oxide nanoparticles (SPION), bromodeoxyuridine (BrdU) or green fluorescent protein (GFP) are frequently used to study the fate of transplanted cells by in vivo magnetic resonance imaging or fluorescent microscopy. Bystander uptake of labeled cells by resident tissue macrophages (TM) can confound the interpretation of the presence of intracellular labels especially during direct implantation of cells, which can result in more than 70% cell death. In this study we determined the percentages of TM that took up SPION, BrdU or GFP from labeled bone marrow stromal cells (BMSCs) that were placed into areas of angiogenesis and inflammation in a mouse model known as Matrigel plaque perfusion assay. Cells recovered from digested plaques at various time points were analyzed by fluorescence microscopy and flow cytometry. The analysis of harvested plaques revealed 5% of BrdU(+), 5-10% of GFP(+) and 5-15% of dextran(+) macrophages. The transfer of the label was not dependent on cell dose or viability. Collectively, this study suggests that care should be taken to validate donor origin of cells using an independent marker by histology and to assess transplanted cells for TM markers prior to drawing conclusions about the in vivo behavior of transplanted cells.

Current method to magnetically label cells using ferumoxides (Fe)-protamine (Pro) sulfate (FePro) is based on generating FePro complexes in a serum free media that are then incubated overnight with cells for the efficient labeling. However, this labeling technique requires long (>12-16 hours) incubation time and uses relatively high dose of Pro (5-6 microg/ml) that makes large extracellular FePro complexes. These complexes can be difficult to clean with simple cell washes and may create low signal intensity on T2* weighted MRI that is not desirable. The purpose of this study was to revise the current labeling method by using low dose of Pro and adding Fe and Pro directly to the cells before generating any FePro complexes. Human tumor glioma (U251) and human monocytic leukemia cell (THP-1) lines were used as model systems for attached and suspension cell types, respectively and dose dependent (Fe 25 to 100 microg/ml and Pro 0.75 to 3 microg/ml) and time dependent (2 to 48 h) labeling experiments were performed. Labeling efficiency and cell viability of these cells were assessed. Prussian blue staining revealed that more than 95% of cells were labeled. Intracellular iron concentration in U251 cells reached approximately 30-35 pg-iron/cell at 24 h when labeled with 100 microg/ml of Fe and 3 microg/ml of Pro. However, comparable labeling was observed after 4 h across the described FePro concentrations. Similarly, THP-1 cells achieved approximately 10 pg-iron/cell at 48 h when labeled with 100 microg/ml of Fe and 3 microg/ml of Pro. Again, comparable labeling was observed after 4 h for the described FePro concentrations. FePro labeling did not significantly affect cell viability. There was almost no extracellular FePro complexes observed after simple cell washes. To validate and to determine the effectiveness of the revised technique, human T-cells, human hematopoietic stem cells (hHSC), human bone marrow stromal cells (hMSC) and mouse neuronal stem cells (mNSC C17.2) were labeled. Labeling for 4 hours using 100 microg/ml of Fe and 3 microg/ml of Pro resulted in very efficient labeling of these cells, without impairing their viability and functional capability. The new technique with short incubation time using 100 microg/ml of Fe and 3 microg/ml of Pro is effective in labeling cells for cellular MRI.

In the title compound, C19H34N+·Br−·H2O, the dihedral angle between the trans-planar alkyl side chain and the pyridinium ring is 52.73 (7)°. In the crystal structure, O—H...Br, C—H...Br and C—H...O hydrogen bonds form a network, while the hydrophobic alkyl chains interdigitate, forming bilayers.

Abstract Goals of work  Comparing antiemetic efficacy of different 5-HT3-receptor antagonists (5-HT3RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV). Patients and methods  Comparisons between 5-HT3RAs were based on 44 randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non-cisplatin-based). Main results  When all studies were combined, granisetron was equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p = 0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron (n = 3) revealed equivalence in each comparison. An advantage for 3 mg granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p = 0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin-based trials (n = 6). No differences were seen between 3 and 1 mg granisetron doses (n = 6). Conclusions  Efficacy of 5-HT3RAs for preventing CINV following cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception of granisetron vs tropisetron. Some differences were noted in dosing subanalyses. [ABSTRACT FROM AUTHOR]

Objectives. To determine the effect of newly developed knee pain on general health and physical function of people ≥50 yrs living in the community.Methods. Prospective cohort study of 3907 people aged 50 registered with three general practices in North Staffordshire, in the UK. The main outcome measures were self-reported knee pain; general health and physical function as measured by the Short Form 36 (SF-36).Results. Of those with no knee pain at baseline, 24% (n = 501) reported it at follow-up. There was a steep decline in physical function in this group (mean fall in SF-36 score at follow-up 10.3 points) compared with the 1558 persons who had no knee pain at baseline or follow-up (mean fall 3.3). Those with knee pain at baseline whose pain had resolved at 3-yr follow-up (n = 409) showed only minor improvements in physical functioning scores at follow-up (mean improvement −1.3).Conclusions. The onset of knee pain is associated with a substantial and persistent reduction of physical function in older adults living in the community. Since knee pain is common, and reduced physical function in mid to older ages is a strong predictor of future disability and dependency, effective prevention or early treatment of knee pain at these ages is likely to have a major influence on healthy ageing in the population. [ABSTRACT FROM AUTHOR]

Objective. To develop a stepped model of care for the treatment of knee pain in older adults in primary care based on recommended interventions.Methods. A systematic search was undertaken to identify interventions recommended for knee osteoarthritis or knee pain in clinical guidelines and systematic reviews. Following this, a nominal group consensus exercise was conducted with members of the Primary Care Rheumatology Society to allocate the interventions to a stepped model of care.Results. Twenty-seven recommended interventions were identified from 77 publications following the systematic search. A four-step model of care incorporating these interventions was developed through the consensus exercise. Step 1 comprised ten interventions that should be offered to all older adults with knee pain, but could also be provided through self-care. These included exercise, weight loss, paracetamol and written information. Steps 2 and 3 comprised 10 and 6 interventions, respectively, to be considered for people with persisting pain and disability. These included pharmacological interventions such as non-steroidal anti-inflammatory drugs in step 2 and intra-articular corticosteroids in step 3, and non-pharmacological interventions such as physiotherapy in step 2 and occupational therapy in step 3. Step 4 was referral for surgery.Conclusions. Previous evidence-based guidelines for the treatment of knee problems have been developed in secondary care. A systematic search for recommended interventions, and a consensus exercise, has now enabled an evidence-based and practical model of care for knee pain in older adults to be developed for use in primary care. [ABSTRACT FROM AUTHOR]

Clinicians often request patients to perform movements of joints as an aid to assessment and diagnosis of many diseases. However, patients may perform abnormal secondary movements where their primary movement is limited. A new measuring system, the FASTRAK, has the potential to measure movement in three dimensions, and to measure movements of the body away from the primary movement. This paper explores the use of multilevel modelling to describe the patterns of movement where subjects are measured on several occasions for both a non-diseased group and for a group of subjects suffering from ankylosing spondylitis. Three-level multilevel models are described with level 3 being the subjects, level 2 being the measurement occasions (up to three) and level 1 being the measurements (three) on each occasion. The models highlight which are the most important secondary movements during the primary movement and show clinically interpretable patterns of movement that can highlight differences between diseased and non-diseased groups. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An abstract of the study "College Student Organ Donation Study: Intervention to Increase Awareness and Registration," by S. Disena, K. Jordan, M. Lindsay and B. Granger is presented.

Objectives. To describe the treatment of knee pain in older adults in primary care and to compare reported practice with published evidence. Methods. A semi-structured interview of older adults with knee pain about their use of 26 interventions for knee pain. Results. 201 adults were interviewed. A median of six interventions had been advised for each participant, with heat and ice (84%) the most frequently advised, followed by paracetamol (71%), compound opioid analgesics (59%) and non-selective non-steroidal anti-inflammatory drugs (59%). Three core treatments for knee pain (written information, exercise and weight loss) were advised to 16%, 46% and 39% of the participants, respectively. Half of the interventions had been initiated through ‘self care’. Most core treatments had not been initiated before second-line interventions had been used, paracetamol being the exception. Referral to surgery was commonly initiated before more conservative options had been tried. Conclusions. Interventions recommended as core treatment for knee pain in older adults were underused—in particular, exercise, weight loss and the provision of written information. There appeared to be early reliance on pharmacological treatments with underuse of non-pharmacological interventions in early treatment choices. Self care played an important role in the management of this condition. The study provides clear evidence on the need to improve the delivery of core treatments for osteoarthritis and highlights the need to support and encourage self care. [ABSTRACT FROM AUTHOR]

The cysteine proteases falcipain-2 and falcipain-3 are hemoglobinases and potential targets for chemotherapy directed against Plasmodium falciparum, the most important human malaria parasite. Most in vivo evaluations of candidate antimalarials are conducted in murine malaria models, and falcipain homologs from rodent malaria parasites differ importantly from falcipain-2 and falcipain-3. We expressed berghepain-2, the single homolog of falcipain-2 and falcipain-3 of the rodent parasite P. berghei, in Escherichia coli, and characterized the refolded active enzyme. Berghepain-2 was biochemically very similar to the previously characterized rodent plasmodial protease vinckepain-2, but differed from falcipain-2 and falcipain-3 in its fine substrate and inhibitor specificity. We then used homology modeling and evolutionary trace analysis to predict key amino acids that mediate functional differences between falcipain-2 and berghepain-2. Thirteen amino acids were sequentially altered to replace berghepain-2 residues with those in falcipain-2. Mutant enzymes varied in activity and sensitivity to inhibitors. A berghepain-2 mutant with eight substitutions retained good activity and demonstrated fine substrate and inhibitor sensitivity more similar to that of falcipain-2 than berghepain-2. These results suggest that, to facilitate drug discovery, we can produce mutant animal model malaria parasites with biochemical properties more like those of the key drug target, P. falciparum. [ABSTRACT FROM AUTHOR]

Abstract Objectives: To determine the extent of observer agreement in diagnosis of oral epithelial dysplasia (OED). Published studies of OED examiner agreement report relatively low agreement levels; however, these studies were limited by the methodologies employed. Methods: For this study, 64 slides were each independently examined twice by three oral pathologists. Consistency was assessed by determining intra- and interexaminer agreement. Conformity was assessed by using the modal diagnosis as a gold standard. Results: The group showed moderate interobserver agreement when grading the presence or absence of OED with a group-simple kappa (K s) of 0.51 (95% CI = 0.42–0.61), and substantial agreement when using a 5-point ordinal scale with a group-weighted kappa (K w) of 0.74 (95% CI = 0.64–0.85). The group showed fair to substantial intraexaminer agreement when assessing the presence or absence of OED, with K s ranging from 0.22 to 0.78, and showing almost a perfect agreement using a 5-point ordinal scale, with K w ranging from 0.82–0.96. Conformity with the comparison standard modal diagnosis was almost perfect, with pairwise K w ranging from 0.81 to 0.92. Conclusion: Overall, there was substantial intra- and interobserver consistency and almost perfect conformity in the grading of OED. Appropriate statistical methods are necessary to determine the degree of observer agreement. [ABSTRACT FROM AUTHOR]