Scribe: A Clustering Approach To Semantic Information Retrieval

Information retrieval is the process of fulfilling a user?s need for information by locating items in a data collection that are similar to a complex query that is often posed in natural language. Latent Semantic Indexing (LSI) was the predominant technique employed at the National Institute of Standards and Technology?s Text Retrieval Conference for many years until limitations of its scalability to large data sets were discovered. This thesis describes SCRIBE, a modification of LSI with improved scalability. SCRIBE clusters its semantic index into discrete volumes described by high-dimensional extensions to computer graphics data structures. SCRIBE?s clustering strategy limits the number of items that must be searched and provides for sub-linear time complexity in the number of documents. Experimental results with a large, natural language document collection demonstrate that SCRIBE achieves retrieval accuracy similar to LSI but requires 1/10 the time

Vimentin Is a Novel Anti-Cancer Therapeutic Target; Insights from In Vitro and In Vivo Mice Xenograft Studies

BACKGROUND:Vimentin is a ubiquitous mesenchymal intermediate filament supporting mechano-structural integrity of quiescent cells while participating in adhesion, migration, survival, and cell signaling processes via dynamic assembly/disassembly in activated cells. Soft tissue sarcomas and some epithelial cancers exhibiting "epithelial to mesenchymal transition" phenotypes express vimentin. Withaferin-A, a naturally derived bioactive compound, may molecularly target vimentin, so we sought to evaluate its effects on tumor growth in vitro and in vivo thereby elucidating the role of vimentin in drug-induced responses. METHODS AND FINDINGS:Withaferin-A elicited marked apoptosis and vimentin cleavage in vimentin-expressing tumor cells but significantly less in normal mesenchymal cells. This proapoptotic response was abrogated after vimentin knockdown or by blockade of caspase-induced vimentin degradation via caspase inhibitors or overexpression of mutated caspase-resistant vimentin. Pronounced anti-angiogenic effects of Withaferin-A were demonstrated, with only minimal effects seen in non-proliferating endothelial cells. Moreover, Withaferin-A significantly blocked soft tissue sarcoma growth, local recurrence, and metastasis in a panel of soft tissue sarcoma xenograft experiments. Apoptosis, decreased angiogenesis, and vimentin degradation were all seen in Withaferin-A treated specimens. CONCLUSIONS:In light of these findings, evaluation of Withaferin-A, its analogs, or other anti-vimentin therapeutic approaches in soft tissue sarcoma and "epithelial to mesenchymal transition" clinical contexts is warranted

A methodology for projecting hospital bed need: a Michigan case study

Michigan's Department of Community Health (MDCH) is responsible for managing hospitals through the utilization of a Certificate of Need (CON) Commission. Regulation is achieved by limiting the number of beds a hospital can use for inpatient services. MDCH assigns hospitals to service areas and sub areas by use patterns. Hospital beds are then assigned within these Hospital Service Areas and Facility Sub Areas. The determination of the number of hospital beds a facility subarea is authorized to hold, called bed need, is defined in the Michigan Hospital Standards and published by the CON Commission and MDCH. These standards vaguely define a methodology for calculating hospital bed need for a projection year, five years ahead of the base year (defined as the most recent year for which patient data have been published by the Michigan Hospital Association). MDCH approached the authors and requested a reformulation of the process. Here we present a comprehensive guide and associated code as interpreted from the hospital standards with results from the 2011 projection year. Additionally, we discuss methodologies for other states and compare them to Michigan's Bed Need methodology

The impact of psychological factors on recovery from injury: a multicentre cohort study

Purpose Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. Methods A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. Results A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. Conclusions Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury

‘Playing’ with Evidence: combining creative co-design methods with realist evidence synthesis

Breaking the cycle of declining physical function and physical activity can improve health and independence for people with long-term conditions. Services within primary care are well placed to empower individuals and communities to achieve this. However, the best approach is uncertain, and must consider needs of people with long-term conditions and complexities of service delivery. This study aimed to understand how to reduce decline in physical function and physical activity in people with long-term conditions. We used realist methods integrated with co-design to provide an explanatory account of what works (or does not), for whom and in what circumstances, to generate ideas about service innovation, and provide recommendations for primary care. A key aspect was tracking evidence from different sources, presenting it creatively by converting it into physical games, enabling stakeholders to ‘play with’ and make-sense of it, to inform co-design work, enabling them to draw upon their own experiences and a wider understanding. In this article, we focus on the game activities, adding to the co-design games’ literature and suggest that this expands participants’ knowledge base beyond their experiences, empowering them to contribute more to the process and creating a strong link between the realist and co-design methods

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi

Facilitators and barriers to physical activity following pulmonary rehabilitation in COPD: a systematic review of qualitative studies

Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level. This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation. This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation. Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD. Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes. Fourteen studies including 167 COPD patients met the inclusion criteria. Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation. These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine. These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment. The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD

Preparing for a community-based agriculture-to-nutrition trial in rural Malawi: formative research to assess feasibility and inform design and implementation decisions.

BACKGROUND: This study reports findings from formative research conducted to assess the feasibility and inform the design and implementation of the Addressing Hidden Hunger with Agronomy (AHHA) trial. The AHHA trial was a randomised, controlled trial conducted in rural Malawi, in which participants were given maize flour biofortified with selenium or control flour not biofortified with selenium for a period of 10 weeks, after which blood samples were taken to measure selenium status. METHODS: Formative research was conducted in villages near to the AHHA trial study site 1 year before the planned intervention. A short questionnaire with adult women (n = 50), focus group discussions with male (n groups = 3) and female (n groups = 3) community members, and in-depth key informant interviews (n = 7) were conducted to understand community practices and perceptions. FINDINGS: Meals were typically cooked and eaten at home in this community, while participants reported that maize flour would be less readily sold than maize grain - important considerations for the design of the trial. Regarding intervention delivery, we identified potential concerns around effects on fertility, links between blood sampling and witchcraft, and the potential for social stigma if community members considered participants lazy for receiving free flour. Participants reported that involvement of the Malawi government partners including health extension workers would increase trust. INTERPRETATION: Following the formative research, the AHHA trial appeared feasible. However, community sensitisation would be essential to address potential fears and concerns; effective sensitisation would support recruitment and treatment adherence, and would protect the safety and wellbeing of participants and researchers. People in positions of authority and trust including village headmen, religious leaders, health and agriculture extension workers, and community care groups should be involved in community sensitisation

Macrofilaricidal Activity after Doxycycline Only Treatment of Onchocerca volvulus in an Area of Loa loa Co-Endemicity: A Randomized Controlled Trial

The control of onchocerciasis in Africa relies on the sustained delivery of ivermectin. In certain areas, annual treatments delivered with high population coverage for at least 15–17 years can break transmission. In other endemic settings this strategy alone is thought to be insufficient to eradicate the disease. One of the major limitations occurs in areas that are co-endemic with another filarial infection caused by Loa loa, due to the risk of a rare severe adverse event associated with the rapid killing of L. loa microfilariae in heavily parasitized individuals. There are also concerns over recent evidence of reduced efficacy of ivermectin and the possible development of resistance. An alternative approach is to target the Wolbachia bacterial endosymbionts of Onchocerca volvulus with the antibiotic, doxycycline. In an area of Cameroon co-endemic for onchocerciasis and loiasis we conducted a trial comparing doxycycline with or without ivermectin treatment to ivermectin treatment alone. A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. The trial indicates that anti-wolbachial therapy is a feasible alternative to ivermectin in communities co-endemic for onchocerciasis and loiasis