531 research outputs found
Development of an algorithm for determining smoking status and behaviour over the life course from UK electronic primary care records
A framework for mixing methods in quantitative measurement development, validation, and revision: A case study
A framework for quantitative measurement development, validation, and revision that incorporates both qualitative and quantitative methods is introduced. It extends and adapts Adcock and Collier’s work, and thus, facilitates understanding of quantitative measurement development, validation, and revision as an integrated and cyclical set of procedures best achieved through mixed methods research. It also offers a systematic guide concerning how these procedures may be undertaken through detailing key “stages,” “levels,” and practical “tasks.” A case study illustrates how qualitative and quantitative methods may be mixed through the use of the proposed framework in the cross-cultural content- and construct-related validation and subsequent revision of a quantitative measure.The contribution of this article to mixed methods research literature is briefly discussed
Learning Sequences: Their Existence, Effect, and Evolution
Much is known about the importance of learning and some of the distinct learning processes that organizations use (e.g., trial-and-error learning, vicarious learning, experimental learning, and improvisational learning). Yet surprisingly little is known about whether these processes combine over time in ordered ways, because most research on learning explores one particular process. Using theory elaboration and theory-building methods and data on the accumulated country entries of entrepreneurial firms, we address this gap. Our core contribution is an emergent theoretical framework that develops the concept of learning sequences. We find that learning sequences exist and are influenced by initial conditions. We also find that learning sequences evolve in fundamentally distinct ways over time and with repeated use. Finally, data show how different learning sequences differentially affect both shorter- and longer-term performance, suggesting that it matters which learning processes are used and when. Overall, our findings on learning sequences have important implications for learning theory, international entrepreneurship, and the growing literature on process management
Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation
Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration
Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case–control study
Association between mortality from suicide in England and antidepressant prescribing: an ecological study
BACKGROUND: Antidepressant prescribing has been increasing in England. Studies in other countries suggest that while this may be associated with reduced suicide rates, it may also be associated with increased fatal poisoning from antidepressant drugs. We therefore conducted an ecological study to assess the association between prescription rates for antidepressants and suicide or fatal antidepressant-related poisoning in England. METHODS: The Office for National Statistics provided information on the number of suicides, antidepressant-related poisoning deaths and populations for England between 1993 and 2002. The Department of Health supplied data on prescriptions for all antidepressants dispensed in England. Associations between prescriptions and deaths were assessed using Spearman's rank correlation coefficient. RESULTS: There were 46,747 suicides, 3,987 deaths involving tricyclic antidepressants and 430 involving selective serotonin re-uptake inhibitors and other antidepressants. Increased antidepressant prescribing was statistically associated with a fall in suicide rates (Spearman's r(s )= -0.73, p = 0.02) and fatal poisoning involving tricyclic antidepressants (r(s )= -0.64, p = 0.05). In contrast, increased prescribing of selective serotonin re-uptake inhibitors and other antidepressants was statistically associated with an increase in fatal poisoning involving these drugs (r(s )= 0.99, p < 0.001). CONCLUSION: Increased prescribing of antidepressants may indicate improved diagnosis and treatment of depression in primary care. Our analysis suggests that this was accompanied by lower suicide rates. A decrease in poisoning deaths involving tricyclic antidepressants may suggest a change in preference for using serotonin reuptake inhibitors and other antidepressant drugs for high-risk patients. This may also partially explain the increase in deaths involving these drugs. Due to the ecological nature of the design, we cannot say conclusively whether reduced suicide rates are a direct consequence of increased antidepressant prescribing rates. To confirm these associations, individual level data on prescribing and suicide is needed
An increased risk of urinary tract infection precedes development of primary biliary cirrhosis
BACKGROUND: Primary Biliary Cirrhosis is known to be associated with Urinary Tract Infections (UTIs), but whether these precede or follow the liver disease is unclear. We have therefore attempted to determine whether UTIs are more common in people with Primary Biliary Cirrhosis (PBC) prior to their diagnosis.METHODS: We conducted a case control study in the General Practice Research Database. All cases of PBC first recorded at least one year after entry to the dataset were selected along with up to 10 controls matched for age, sex. A second unmatched control group who had Chronic Liver Diseases but not PBC were chosen. The main exposures studied were the occurrence of Urinary tract infections and pyelonephritis at least one or at least five years before diagnosis. We also performed an analysis restricted to those younger than 55 at diagnosis, as we hypothesized the relationship to be stronger in the younger age group.RESULTS: PBC is associated with UTI prior to diagnosis, OR 1.50 (CI 1.26-1.78), which was similar 5 years prior to diagnosis and after adjusting for smoking. The strongest relationships were observed in pyelonephritis exposures five years before diagnosis in cases under 55 years: adjusted odds ratios were 2.60 (1.02-6.63) in comparison with matched general population controls and adjusted odds ratios were OR 2.45 (1.02-5.59) in the comparison with chronic liver disease controls.CONCLUSIONS: We found that the association between urosepsis and PBC is specific to this disease and precedes the diagnosis of PBC in a manner not previously observed in human data. This is consistent with a causal relationship.</p
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
AIMS/HYPOTHESIS: The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues.
METHODS: This was a retrospective cohort study of people treated in UK general practices. Those included in the analysis developed diabetes >40 years of age, and started treatment with oral agents or insulin after 2000. A total of 62,809 patients were divided into four groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. Insulin users were grouped according to treatment with insulin glargine, long-acting human insulin, biphasic analogue and human biphasic insulin. The outcome measures were progression to any solid tumour, or cancer of the breast, colon, pancreas or prostate. Confounding factors were accounted for using Cox proportional hazards models.
RESULTS: Metformin monotherapy carried the lowest risk of cancer. In comparison, the adjusted HR was 1.08 (95% CI 0.96-1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19-1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27-1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43-0.66). The risk for those on basal human insulin alone vs insulin glargine alone was 1.24 (95% CI 0.90-1.70). Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23-2.33) or pancreatic cancer (HR 4.63, 95% CI 2.64-8.10), but did not influence the risk of breast or prostate cancer. Sulfonylureas were associated with a similar pattern of risk as insulin.
CONCLUSIONS/INTERPRETATION: Those on insulin or insulin secretagogues were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin
Bringing Japanese Continuous Improvement Approaches to U.S. Manufacturing: The Roles of Process Orientation and Communications *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71419/1/j.1540-5915.1995.tb01442.x.pd
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