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Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans↗

Royal Society of Tropical Medicine and Hygiene Meeting at Manson House, London, 12 December 1996. HIV and pneumococcal infection in Africa. Microbiological aspects.

By the 1930s several studies had shown that Streptococcus pneumoniae was an important pathogen in Nairobi (Kenya) and various risk factors for infection were recognized, including seasonally cold conditions, overcrowding and recent arrival in the city. Research into pneumococcal disease declined with the arrival of penicillin but recently interest has been rekindled by recognition of the pneumococcus as a human immunodeficiency virus (HIV)-associated pathogen and by the emergence of antibiotic resistance. The pneumococcus and its association with HIV were studied during the course of the Wellcome Trust/Kenya Medical Research Institute HIV Programme in Nairobi (1988-1993). There were generally high rates of pneumococcal disease. The pneumococcus (with tuberculosis and salmonellosis) was a major HIV-related pathogen. One study showed HIV seropositivity to confer a relative risk of 17.8 for pneumococcal infection. Recurrent infection accounted for a large proportion (25%) of disease episodes in a longitudinally studied cohort of HIV patients. There were higher pneumococcal carriage rates in HIV-positive than in HIV-negative patients (28% vs. 16%, P = 0.003). High rates of resistance were found to penicillin (25%). Molecular characterization of penicillin-resistant strains identified 11 separate clones, showing great genetic diversity in a small sample of isolates, and there was evidence of horizontal spread of penicillin-binding protein genes between separate lineages. Molecular characterization of isolates from patients with recurrent disease suggested that both relapse and reinfection might occur. There was molecular evidence of transfer of capsular genes between clones (serotype switching). The overall spectrum of serotypes resembled those reported elsewhere, most serotypes being included in the 23-valent vaccine. Higher numbered serotypes were associated with respiratory tract source and antibiotic resistance. Various methods were used to show 82% concordance between pernasal and blood isolates in pneumonia cases. HIV-seropositive patients were more prone to infection with penicillin- and tetracycline-resistant organisms than seronegative patients (penicillin, 27% vs. 7%; tetracycline, 40% vs. 17%), a difference reflected by different serotype profiles in the 2 groups. These studies highlight the importance of the pneumococcus as an HIV-related pathogen in one part of Africa. The high rates of antibiotic resistance are a cause of concern. There should be continued monitoring of resistance patterns, and assessments of the significance of pneumococcal disease made elsewhere in Africa are to be encouraged.

Cohort Studies↗

Structural complexity effects on transverse propagation in a two-dimensional model of myocardium.

A thin sheet of cardiac tissue was modeled as a set of resistively coupled excitable cables with membrane dynamics described by the modified Beeler Reuter model. Transverse connections have a resistance Rn and are regularly distributed with a spacing delta on any given cable, to provide alternating input and output junctions. Flat wave longitudinal propagation corresponds to propagation along a single continuous cable since all units of the network are functionally isolated due to the absence of transverse current flow. Events on a given cable during flat transverse propagation include electrotonic spread of potential from input to output junctions, action potential initiation at input junctions, and collision at output junctions. The propagating two-dimensional transverse wavefront is an undulating transmembrane potential surface with highs at the input junctions and lows at the output junctions. The action potential upstroke is also modulated in a periodic manner with minimum and maximum Vmax at the input and output junctions respectively. Thus, the network is capable of a diversity of dynamic behavior spatially distributed in relation to the specific pattern of transverse connections chosen. Overall, the behavior of the network model is in good agreement with available structural and electrophysiological data on myocardium. In addition, this network topology allows to handle more easily parameters governing propagation and to avoid very large matrices which are costly in computational effort and overall computer time.

Computer Simulation↗

Characterization of a shiga toxin-, intimin-, and enterotoxin hemolysin-producing Escherichia coli ONT:H25 strain commonly isolated from healthy cattle.

Among bovine fecal and recto-anal mucosal swab samples cultured in our laboratory for Escherichia coli O157:H7, we frequently isolated E. coli organisms that were phenotypically similar to the O157:H7 serotype as non-sorbitol fermenting and negative for beta-glucuronidase activity but serotyped O nontypeable:H25 (ONT:H25). This study determined the prevalence and virulence properties of the E. coli ONT:H25 isolates. Among dairy and feedlot cattle (n = 170) sampled in Washington, Idaho, and Alberta, Canada, the percentage of animals culture positive for E. coli ONT:H25 ranged from 7.5% to 22.5%, compared to the prevalence of E. coli O157:H7 that ranged from 0% to 15%. A longitudinal 8-month study of dairy heifers (n = 40) showed that 0 to 15% of the heifers were culture positive for E. coli O157:H7, while 15 to 22.5% of the animals were culture positive for E. coli ONT:H25. As determined by a multiplex PCR, the E. coli ONT:H25 isolates carried a combination of virulence genes characteristic of the enterohemorrhagic E. coli, including intimin, translocated intimin receptor, Stx2, and hemolysin (eae-beta, tir, stx(2vh-a), and hly). E. coli ONT:H25 isolates from diverse geographic locations and over time were fingerprinted by separating XbaI-restricted chromosomal DNA by pulsed-field gel electrophoresis (PFGE) separation. Two strains of E. coli ONT:H25 were highly similar by PFGE pattern. Experimental inoculation of cattle showed that E. coli ONT:H25, like E. coli O157:H7, colonized the bovine recto-anal junction mucosa for more than 4 weeks following a single rectal application of bacteria.

Adhesins, Bacterial↗

Ethnic disparities in diabetic complications in an insured population.

CONTEXT: Higher rates of microvascular complications have been reported for minorities. Disparate access to quality health care is a common explanation for ethnic disparities in diabetic complication rates in the US population. Examining an ethnically diverse population with uniform health care coverage may be useful. OBJECTIVE: To assess ethnic disparities in the incidence of diabetic complications within a nonprofit prepaid health care organization. DESIGN AND SETTING: Longitudinal observational study conducted January 1, 1995, through December 31, 1998, at Kaiser Permanente Medical Care Program in northern California. PARTICIPANTS: A total of 62 432 diabetic patients, including Asians (12%), blacks (14%), Latinos (10%), and whites (64%). MAIN OUTCOME MEASURES: Incident myocardial infarction (MI), stroke, congestive heart failure (CHF), and nontraumatic lower extremity amputation (LEA), defined by primary hospitalization discharge diagnosis, procedures, or underlying cause of death; and end-stage renal disease (ESRD), defined as renal insufficiency requiring renal replacement therapy or transplantation for survival or by underlying cause of death. RESULTS: Patterns of ethnic differences were not consistent across complications and frequently persisted despite adjustment for a wide range of demographic, socioeconomic, behavioral, and clinical factors. Adjusted hazard ratios (relative to that of whites) were 0.56, 0.68, and 0.68 for blacks, Asians, and Latinos, respectively (P<.001), for MI; 0.76 and 0.72 for Asians and Latinos, respectively (P<.01), for stroke; 0.70 and 0.61 for Asians and Latinos, respectively (P<.01), for CHF; 0.40 for Asians (P<.001) for LEA; and 2.03, 1.85, and 1.46 for blacks, Asians, and Latinos, respectively (P<.01), for ESRD. There were no statistically significant black-white differences for stroke, CHF, or LEA and no Latino-white differences for LEA. CONCLUSIONS: This study confirms previous reports of elevated incidence of ESRD among ethnic minorities, despite uniform medical care coverage, and provides new evidence that rates of other complications are similar or lower relative to those of whites. The persistence of ethnic disparities after adjustment suggests a possible genetic origin, the contribution of unmeasured environmental factors, or a combination of these factors.

Amputation, Surgical↗

Epidemiology of fascioliasis in human endemic areas.

Considered a secondary zoonotic disease until the mid-1990s, human fascioliasis is at present emerging or re-emerging in many countries, including increases of prevalence and intensity and geographical expansion. Research in recent years has justified the inclusion of fascioliasis in the list of important human parasitic diseases. At present, fascioliasis is a vector-borne disease presenting the widest known latitudinal, longitudinal and altitudinal distribution. Fasciola hepatica has succeeded in expanding from its European original geographical area to colonize five continents, despite theoretical restrictions related to its biology and in turn dependent upon environmental and human activities. Among the different epidemiological situations, human hypo- to hyperendemic areas, including epidemics, are noteworthy. A global analysis of the distribution of human cases shows that the expected correlation between animal and human fascioliasis only appears at a basic level. Areas presenting very high human prevalences and intensities, especially in children and females, have been recently described. In hypo- to hyperendemic areas of Central and South America, Europe, Africa and Asia, human fascioliasis presents a range of epidemiological characteristics related to a wide diversity of environments. Thus far well-known epidemiological patterns of fascioliasis may not always explain the transmission characteristics in any given area and control measures should consider the results of ecoepidemiological studies undertaken in the zones concerned.

Altitude↗

A statistical characterization of consistent patterns of human immunodeficiency virus evolution within infected patients.

Within-patient HIV populations evolve rapidly because of a high mutation rate, short generation time, and strong positive selection pressures. Previous studies have identified "consistent patterns" of viral sequence evolution. Just before HIV infection progresses to AIDS, evolution seems to slow markedly, and the genetic diversity of the viral population drops. This evolutionary slowdown could be caused either by a reduction in the average viral replication rate or because selection pressures weaken with the collapse of the immune system. The former hypothesis (which we denote "cellular exhaustion") predicts a simultaneous reduction in both synonymous and nonsynonymous evolution, whereas the latter hypothesis (denoted "immune relaxation") predicts that only nonsynonymous evolution will slow. In this paper, we present a set of statistical procedures for distinguishing between these alternative hypotheses using DNA sequences sampled over the course of infection. The first component is a new method for estimating evolutionary rates that takes advantage of the temporal information in longitudinal DNA sequence samples. Second, we develop a set of probability models for the analysis of evolutionary rates in HIV populations in vivo. Application of these models to both synonymous and nonsynonymous evolution affords a comparison of the cellular-exhaustion and immune-relaxation hypotheses. We apply the procedures to longitudinal data sets in which sequences of the env gene were sampled over the entire course of infection. Our analyses (1) statistically confirm that an evolutionary slowdown occurs late in infection, (2) strongly support the immune-relaxation hypothesis, and (3) indicate that the cessation of nonsynonymous evolution is associated with disease progression.

Acquired Immunodeficiency Syndrome↗

Maternal interaction patterns and preschool competence in high-risk children.

BACKGROUND: The influence of specific maternal interaction patterns as compensatory mechanisms in promoting development of medically high-risk children has been understudied. OBJECTIVES: To investigate the association of three maternal interaction patterns, maternal responsivity, involvement, and control style, with preschool competency in a medically heterogeneous sample. METHOD: Children (N= 184) and their mothers participating in a prospective longitudinal study were assessed in a laboratory protocol and home visit. The methods of measurement were maternal self-report, global rating scales, interview, and nationally standardized instruments. RESULTS: Evidence of a maternal compensatory mechanism was exhibited in mothers' higher involvement with their children who were born at high medical risk (F(1,183) = 6.26, p = .01). Mothers of the most competent children demonstrated higher maternal responsivity, involvement, and more appropriate control than mothers of children who were not as competent. In hierarchical regression models, the three maternal interaction patterns were significant predictors after perinatal risk and maternal education were controlled explaining 29-37% of the variance in child competence scores. CONCLUSION: These findings imply that differential child outcomes are associated with specific maternal interaction patterns. It suggests that a combination of diverse information revealed in specific maternal interaction pattern is needed to predict cognitive, linguistic, and problem-solving competencies. Future research should consider individual differences in mother-child interaction patterns in order to isolate their significance for optimal child development.

Adult↗

NADPH-diaphorase positive myenteric neurons in the ileum of guinea-pig, rat, rabbit and cat: a comparative study.

The nitrergic system of the ileal myenteric plexus of four mammalian species was studied by means of NADPH diaphorase histochemistry which in aldehyde-fixed tissue stains only those cells that contain the constitutive, calcium-dependent nitrogen monoxide synthase isoenzyme. Since previous studies assumed minor species-specific anatomical variations, we sought similarities and differences in the nitrergic innervation pattern of the ileal musculature. In rat and guinea-pig, the ratio of nitrergic cells slightly exceeds 20%, in rabbit it is close to this number (16%), and it is lowest in cat (about 10%). The nitrergic neurons target the circular muscle layer in all investigated species where they participate in inhibitory motoric transmission. Apart from this, some elements of the sensory innervation of the circular musculature may derive from nitrergic neurons in rat and rabbit. The tertiary plexus (longitudinal muscles) is strongly supplied by NADPH diaphorase positive fibres in rat, moderately in guinea-pig and cat and not at all in rabbit. The rest of the nitrergic neurons may serve as inhibitory interneurons and control other (probably excitatory motor) neurons in the myenteric plexus. We conclude that the diverse physiological and pharmacological properties of the nitrergic system described in the small intestine in different species can be connected with the anatomical heterogeneity of its elements.

Animals↗

Three-dimensional chemoarchitecture of the basal forebrain: spatially specific association of cholinergic and calcium binding protein-containing neurons.

The basal forebrain refers to heterogeneous structures located close to the medial and ventral surfaces of the cerebral hemispheres. It contains diverse populations of neurons, including the cholinergic cortically projecting cells that show severe loss in Alzheimer's and related neurodegenerative diseases. The basal forebrain does not display any cytoarchitectural or other structural features that make it easy to demarcate functional boundaries, a problem that allowed different investigators to propose different organizational schemes. The present paper uses novel three-dimensional reconstructions and numerical analyses for studying the spatial organization of four major basal forebrain cell populations, the cholinergic, parvalbumin, calbindin and calretinin containing neurons in the rat. Our analyses suggest that the distribution of these four cell populations is not random but displays a general pattern of association. Within the cholinergic space (i.e. the volume occupied by the cortically projecting cholinergic cell bodies) the three other cell types form twisted bands along the longitudinal axis of a central dense core of cholinergic cells traversing the traditionally defined basal forebrain regions, (i.e. the medial septum, diagonal bands, the substantia innominata, pallidal regions and the bed nucleus of the stria terminalis). At a smaller scale, the different cell types within the cholinergic space occupy overlapping high-density cell clusters that are either chemically uniform or mixed. However, the cell composition of these high-density clusters is regionally specific. The proposed scheme of basal forebrain organization, using cell density or density relations as criteria, offers a new perspective on structure-function relationship, unconstrained by traditional region boundaries.

Acetylcholine↗

Towards genetic markers in animal populations as biomonitors for human-induced environmental change.

Genetic markers provide potentially sensitive indicators of changes in environmental conditions because the genetic constitution of populations is normally altered well before populations become extinct. Genetic indicators in populations include overall genetic diversity, genetic changes in traits measured at the phenotypic level, and evolution at specific loci under selection. While overall genetic diversity has rarely been successfully related to environmental conditions, genetically based changes in traits have now been linked to the presence of toxins and both local and global temperature shifts. Candidate loci for monitoring stressors are emerging from information on how specific genes influence traits, and from screens of random loci across environmental gradients. Drosophila research suggests that chromosomal regions under recent intense selection can be identified from patterns of molecular variation and a high frequency of transposable element insertions. Allele frequency changes at candidate loci have been linked to pesticides, pollutants and climate change. Nevertheless, there are challenges in interpreting allele frequencies in populations, particularly when a large number of loci control a trait and when interactions between alleles influence trait expression. To meet these challenges, population samples should be collected for longitudinal studies, and experimental programmes should be undertaken to link variation at candidate genes to ecological processes.

Adaptation, Physiological↗

Weight teasing and disordered eating behaviors in adolescents: longitudinal findings from Project EAT (Eating Among Teens).

OBJECTIVE: To assess whether weight-related teasing predicts the development of binge eating, unhealthy weight control behaviors, and frequent dieting among male and female adolescents. METHODS: A prospective study was conducted with an ethnically and socioeconomically diverse sample of 2516 adolescents who completed surveys at both time 1 (1998-1999) and time 2 (2003-2004) of the Project EAT (Eating Among Teens) study. RESULTS: In 1998-1999, approximately one fourth of participants reported being teased about their weight at least a few times a year. After adjustment for age, race/ethnicity, socioeconomic status (SES), and BMI, boys who were teased about their weight were more likely than their peers to initiate binge eating with loss of control and unhealthy weight control behaviors 5 years later. The predicted prevalence for incident binge eating behaviors with loss of control among boys who were teased was 4.1% as compared with 1.4% for those who were not teased, after adjustment for age, race/ethnicity, SES, and BMI. For unhealthy weight control behaviors at time 2, the predicted prevalence was 27.5% among boys who were teased and 19.3% for boys who were not teased, after adjustment for age, race/ethnicity, SES, and BMI. Girls who were teased were more likely than their peers to become frequent dieters. The predicted prevalence for incident frequent dieting among girls who were teased was 18.2% as compared with 11.0% for those who were not teased, after adjustment for age, race/ethnicity, SES, and BMI. CONCLUSIONS: Weight teasing in adolescence predicts disordered eating behaviors at 5-year follow-up. The patterns of these associations differ by gender. Reducing teasing through educational interventions and policies may reduce the level of disordered eating behaviors among youths.

Adolescent↗

Brain activation during encoding and recognition of verbal and figural information in older adults.

Positron emission tomography (PET) patterns of cerebral blood flow associated with verbal and figural memory are described in relation to their value as functional probes for studying longitudinal changes that occur in the aging brain. Relative to a matching control task, verbal and figural encoding increase blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and medial temporal, occipital cortex and the cerebellum. Additionally, medial temporal regions exhibited greater activity during figural encoding relative to verbal encoding. During recognition, blood flow increases in prefrontal, cingulate, insular, and lateral temporal and Broca's areas. Analysis of hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally dependent results. Prefrontal region BA 10 demonstrates more bilateral activation during encoding and retrieval, whereas BA 46 shows right greater than left activation during both encoding and retrieval. Overall, the two tasks activate diverse regions within the frontal, temporal and occipital lobes of the brain, including areas that show age-related structural changes, proving their usefulness in the longitudinal assessment of brain function in the elderly.

Aged↗

Alcohol use among college students: the effects of prior problem behaviors and change of residence.

OBJECTIVE: This article examines the relationship between prior problem behaviors and change in residence on alcohol use patterns among college students. METHOD: Measures of alcohol consumption (e.g., drinking frequency, average consumption and frequency of heavy episodic drinking were related to residence patterns and prior problem behaviors (e.g., conduct problems. illicit substance involvement and early age at onset of alcohol consumption). Subjects (N = 2,465; 51% women) were a subsample drawn from the National Longitudinal Study of Labor Market Experience in Youth. The analysis was conducted using a linear growth model for continuous outcomes with time-invariant and time-varying covariates for each of the drinking measures. RESULTS: The results of the structural equation analysis yielded significant and direct effects related to residence patterns and prior problem behaviors. Problem behaviors were related to drinking measures; however, there was no evidence for a mediational hypothesis. Neither was there systematic evidence that the relationship between prior problem behavior and alcohol use was mediated by residence patterns. The analysis of change in residence was related to both time-specific and longer-term influences on alcohol use. CONCLUSIONS: The presence of direct and independent effects for both dispositional and high-risk environmental factors in collegiate drinking practices support targeted and diverse strategies for prevention activities.

Adolescent↗

Antennapedia-class homebox genes define diverse neuronal sets in the embryonic CNS of the leech.

Studies of the Antennapedia-class homeobox genes suggest that specific combinations of these transcription factors play a role in defining neuronal identities. We examined the expression of these genes in the leech Hirudo medicinalis, an organism well-suited for neurobiological research at the level of identified neurons. Leeches contain at least as many Antennapedia-class and related genes as insects do, despite the apparently lower complexity of the leech body plan. The CNS expression patterns of two Antennapedia-class leech homeobox genes (Lox genes) were examined in detail. Lox1 is expressed during early gangliogenesis in only one pair of transient neurons present in every segment (the Bipolar cells) and, at later stages of embryonic development, in 15-20 pairs of central neurons repeated in most segments. The monoclonal antibody Laz1-1 identified two pairs of Lox1-expressing neurons as the Bipolar cells and the L1 neurons. The Bipolar cells extended processes in the primordia of the longitudinal connective nerves and later degenerated. The L1 neurons were detected late in gangliogenesis and became stable neurons. Lox2 is expressed in an iterated set of neurons in the posterior two-thirds of the CNS. On the basis of cell body position and relative size, two pairs of Lox2-expressing cells were identified as the RPE-like neurons and the CV motor neurons. Other Lox genes are also expressed in segmentally repeated subpopulations of neurons. These neuronal subpopulations appear to be different from one another but partially overlapping. Different combinations of Lox genes that may be expressed in individual cells could in theory generate enough variability to specify all central neurons in a leech ganglion.

Animals↗

Anguilliform locomotion in an elongate salamander (Siren intermedia): effects of speed on axial undulatory movements

Many workers interested in the mechanics and kinematics of undulatory aquatic locomotion have examined swimming in fishes that use a carangiform or subcarangiform mode. Few empirical data exist describing and quantifying the movements of elongate animals using an anguilliform mode of swimming. Using high-speed video, I examine the axial undulatory kinematics of an elongate salamander, Siren intermedia, in order to provide data on how patterns of movement during swimming vary with body position and swimming speed. In addition, swimming kinematics are compared with those of other elongate vertebrates to assess the similarity of undulatory movements within the anguilliform locomotor mode. In Siren, most kinematic patterns vary with longitudinal position. Tailbeat period and frequency, stride length, Froude efficiency and the lateral velocity and angle of attack of tail segments all vary significantly with swimming speed. Although swimming speed does not show a statistically significant effect on kinematic variables such as maximum undulatory amplitude (which increases non-linearly along the body), intervertebral flexion and path angle, examination of the data suggests that speed probably has subtle and site-specific effects on these variables which are not detected here owing to the small sample size. Maximum lateral displacement and flexion do not coincide in time within a given tailbeat cycle. Furthermore, the maximum orientation (angle with respect to the animal's direction of forward movement) and lateral velocity of tail segments also do not coincide in time. Comparison of undulatory movements among diverse anguilliform swimmers suggests substantial variation across taxa in parameters such as tailbeat amplitude and in the relationship between tailbeat frequency and swimming speed. This variation is probably due, in part, to external morphological differences in the shape of the trunk and tail among these taxa.

Journal Article↗

The ATTEMPT cohort: a multi-national longitudinal study of predictors, patterns and consequences of smoking cessation; introduction and evaluation of internet recruitment and data collection methods.

AIMS: The ATTEMPT study was designed to chart the natural history of smoking cessation and associated short-term health outcomes and effects on medical resource utilization among a cohort recruited across multiple countries. This paper describes the methods for recruitment and follow-up, the baseline population characteristics of the enrolled population and 1-year response rates. DESIGN: ATTEMPT is a multi-national prospective cohort study that used the internet for subject recruitment and online assessments every 3 months for 2.5 years. SETTING: Subjects were recruited via e-mail from existing internet panels [Canada (n = 208), France (n = 201), the United Kingdom (n = 200) and the United States (n = 1400]. SUBJECTS: Panel members who were aged 35-65 years, smoked at least five cigarettes per day and at initiation stated an intention to quit smoking within the next 3 months were eligible for this study. MEASUREMENTS: Measures included: attempts to quit, smoking status, smoking history, nicotine dependence and craving, methods used to quit smoking, reasons for quitting or failing to quit smoking, short-term health effects, health resource utilization, wellbeing, concern over weight gain, confidence in preventing weight gain, body weight and demographics. In addition, in-home assessments of weight were undertaken by field staff for a random sample of US participants. FINDINGS: Country-specific recruitment was completed within 17 days. The recruitment method produced a sample with characteristics broadly similar to those found in national surveys of smokers except for higher prevalence of obesity in the US and Canadian samples and higher educational level. At the end of 1 year the response rate was 52%, and there was little evidence of differential loss to follow-up by key subject characteristics. Weight reported in the survey was found to correlate highly with weight measured during in-home visits. CONCLUSION: This paper demonstrates the feasibility of enrolling and following a diverse cohort of smokers for self-reported health and behaviour measures via the internet.

Adult↗

The COE transcription factor Collier is a mediator of short-range Hedgehog-induced patterning of the Drosophila wing.

BACKGROUND: The secreted Hedgehog (Hh) proteins have been implicated as mediators of positional information in vertebrates and invertebrates. A gradient of Hh activity contributes to antero-posterior (A/P) patterning of the fly wing. In addition to inducing localised expression of Decapentaplegic (Dpp), which in turn relays patterning cues at long range, Hh directly patterns the central region of the wing. RESULTS: We show that short-range, dose-dependent Hh activity is mediated by activation of the transcription factor Collier (Col). In the absence of col activity, longitudinal veins 3 and 4 (L3 and L4) are apposed and the central intervein is missing. Hh expression induces col expression in a narrow stripe of cells along the A/P boundary through a dual-input mechanism: inhibition of proteolysis of Cubitus-interruptus (Ci) and activation of the Fused (Fu) kinase. Col, in cooperation with Ci, controls the formation of the central intervein by activating the expression of blistered (bs), which encodes the Drosophila serum response factor (D-SRF), the activity of which is required for the adoption and maintenance of the intervein cell fate. Furthermore, col is allelic to knot, a gene involved in the formation of the central part of the wing. This finding completes our understanding of the sectorial organisation of the Drosophila wing. CONCLUSIONS: Col, the Drosophila member of the COE family (Col/Olf-1/EBF) of non-basic, helix-loop-helix (HLH)-containing transcription factors, is a mediator of the short-range organising activity of Hh in the Drosophila wing. Our results support the idea that Hh controls target gene expression in a concentration-dependent manner and highlight the importance of the Fu kinase in this differential regulation. The high degree of evolutionary conservation of the COE proteins and the diversity of developmental processes controlled by Hh signalling raises the possibility that the specific genetic interactions depicted here may also operate in vertebrates.

Alleles↗