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Biomedical subjects

Richard Harvey

Publications and source records attributed to Richard Harvey.

16 recordsLinked to original sources
PubMed2026

Genomic insights into the persistence of Nubian giraffe (Giraffa camelopardalis camelopardalis) in conflict-affected South Sudan.

Armed conflicts can severely disrupt wildlife conservation and management, yet their long-term genomic consequences remain poorly understood. South Sudan has experienced decades of conflict that have limited conservation efforts and prevented genomic assessment of its fauna, including the endangered subspecies of Nubian giraffe (Giraffa camelopardalis camelopardalis). Due to long-standing logistical and political challenges, populations from South Sudan have remained largely unsampled. The Nubian giraffe represents a critical conservation unit and new sampling efforts provide an opportunity to investigate its genomic diversity and potential genetic isolation by the White Nile River, a hypothesized gene flow barrier. Here, we present genomic data from 30 individuals sampled in Boma and Badingilo National Parks in eastern South Sudan. Adding these sequences to existing genomic data reveals genetically distinct groups within the Nubian giraffe according to three regions: Ethiopia-South Sudan, Kenya, Uganda. Despite limited wildlife management due to economic and political constraints in South Sudan, the Nubian giraffe populations have maintained high heterozygosity (He ≈ 0.14%) and minimal evidence of inbreeding (mean FROH ≈ 0.15) compared to Kenya's Nubian giraffe populations. Contrary to expectations, our results reveal measurable gene flow across the White Nile between Nubian giraffe and Kordofan giraffe (G. c. antiquorum). These findings highlight South Sudanese Nubian giraffe as a population that retained genetic diversity and conservation efforts should be enhanced where feasible to ensure this stronghold long-term.

Animals↗
PubMed2006

Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction.

To determine whether gene expression profiling could improve risk classification and outcome prediction in older acute myeloid leukemia (AML) patients, expression profiles were obtained in pretreatment leukemic samples from 170 patients whose median age was 65 years. Unsupervised clustering methods were used to classify patients into 6 cluster groups (designated A to F) that varied significantly in rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1 mutations (78%), normal karyotypes (75%), and genes associated with signaling and apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years). Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%, respectively); cluster B was distinguished by the highest rate of RD (77%) and multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by a "proliferative" gene signature with the highest proportion of detectable cytogenetic abnormalities (76%; including 83% of all favorable and 34% of unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias (97% of cases), also showing increased NPM1 mutations (61%). These gene expression signatures provide insights into novel groups of AML not predicted by traditional studies that impact prognosis and potential therapy.

Acute Disease↗
PubMed2006

Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation.

The intrinsic features of naive CD4 T cells that affect their ability to respond to polarizing signals for Th cell differentiation are not well understood. In this study, we show that naive CD4 T cells from mice transgenic for the Hlx gene expressed lower levels of IL-4Ralpha. The down-regulation of IL-4Ralpha diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4Ralpha with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4Ralpha to favor Th2 cell differentiation. Thus, the IL-4Ralpha level on naive CD4 T cells is genetically controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.

Animals↗
PubMed2006

Same-day transfer of patients with unstable angina and non-ST segment elevation myocardial infarction back to their referring hospital after angioplasty.

BACKGROUND: Recent evidence has shown the advantages of an early invasive strategy for patients with high-risk unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI). However, the number of beds available for postangioplasty monitoring limits the use of this approach at the Centre hospitalier universitaire de Sherbrooke (Fleurimont, Quebec). OBJECTIVES: To study the safety of a protocol allowing the same-day return of patients with UA or NSTEMI to their referring hospital after angioplasty at the Centre hospitalier universitaire de Sherbrooke. METHODS: From June 2001 to June 2003, of the 532 patients with UA and NSTEMI who underwent percutaneous coronary intervention with planned same-day transfer back to their referring hospital, 419 consecutive patients who were eligible to return the same day were prospectively followed for 24 h. RESULTS: Stents were used in 94.7% of patients and platelet glycoprotein IIb/IIIa receptor antagonists were used in 34.8% of patients. For 85% of patients, the femoral artery was used as the access route for percutaneous coronary intervention. The mean time that patients stayed in the hospital after angioplasty before returning to their referring centres was 4.4 h. No deaths, life-threatening arrhythmias or urgent revascularizations were reported during the 24 h postangioplasty follow-up period, but one patient had a major bleeding complication. During the study period, the mean angioplasty waiting time decreased from 5.7 days to 2.1 days. CONCLUSIONS: The protocol evaluated in the present article is safe. It frees more beds, thus reducing the waiting list and allowing patients with high-risk acute coronary syndromes without ST segment elevation from community hospitals to benefit from the advantages of an early invasive strategy.

Adult↗
PubMed2005

In vivo studies of transdisciplinary scientific collaboration Lessons learned and implications for active living research.

The past 2 decades have witnessed a surge of interest and investment in transdisciplinary research teams and centers. Only recently, however, have efforts been made to evaluate the collaborative processes and scientific and public policy outcomes of these endeavors. This paper offers a conceptual framework for understanding and evaluating transdisciplinary research, and describes a large-scale national initiative, the National Institutes of Health Transdisciplinary Tobacco Use Research Centers (TTURCs) program, undertaken to promote cross-disciplinary scientific collaboration in the field of tobacco use science and prevention. A 5-year evaluation of collaborative processes and outcomes observed across multiple TTURC centers conducted during 1999 to 2004 is described. The findings highlight key contextual circumstances faced by participating centers (i.e., the breadth of disciplines and departments represented by each center, the extent to which members had worked together on prior projects, spatial proximity among researchers' offices, and frequency of their face-to-face interaction) that influenced their readiness for collaboration and prompted them to follow different pathways toward transdisciplinary integration. Implications of these findings for developing and evaluating future transdisciplinary research initiatives in the field of active living research are discussed.

Cooperative Behavior↗
PubMed2004

Control of bladder function by peripheral nerves: avenues for novel drug targets.

The micturition reflex involves afferent nerve activation when the bladder is sufficiently full and subsequent controlled firing of parasympathetic efferent nerves to contract the detrusor muscle as part of the voiding mechanism. Alteration of the sensitivity of afferent activation or loss of control over transmitter release could lead to sensory- or motor-activated incontinence, respectively. The control mechanisms that regulate these 2 activities remain poorly understood. Current opinion is that the sensation of bladder fullness is relayed by afferent nerves in the mucosal layer, which are activated by the release of chemical mediators, such as adenosine triphosphate (ATP), from the urothelium when it is stretched as the bladder fills. This hypothesis supports the concept that other chemical signals that affect bladder sensation (eg, changes in urine composition and agents such as capsaicin) can modulate the sensitivity of the basic system. It has also been proposed that a layer of myofibroblasts immediately below the basal lamina of the urothelium acts as a variable gain regulator of the sensory process between ATP release and afferent excitation. These myofibroblasts are functionally connected to form an electrical syncytium, make close contact with nerves, and respond by generating electrical responses and transient increases in intracellular Ca2+ when exposed to ATP. On the efferent side, using a guinea pig detrusor model, possible modulators of transmitter release have been investigated, including adenosine (the breakdown product of the neurotransmitter ATP). Adenosine reduces the force of nerve-mediated contractions by acting predominantly at presynaptic sites at the nerve-muscle junction via a subtype of an adenosine receptor-the A1 receptor. An additional effect, possibly via A2 receptors, is also present on the detrusor muscle itself. These actions of adenosine are less evident in human detrusor muscle but remain a potential modulatory target. In summary, the cellular and molecular regulation of bladder fullness sensation and efferent transmitter release are becoming better understood and represent potential drug targets for the management of detrusor overactivity.

Adenosine↗
PubMed2004

Transdisciplinary collaboration as a basis for enhancing the science and prevention of Substance use and "Abuse".

Transdisciplinary scientific collaborations (TDSCs) have the potential to strengthen substance use and misuse research and prevention. Despite its growing prominence as a mode for scientific research, research on TDSC remains in a nascent form and its value to the field of substance use and misuse merits further exploration. The overarching purpose of this article is to examine the potential contributions of transdisciplinary science to research and prevention using conceptualizations, methods, and evidence from a case study of two university-based research centers. The article provides (a) a discussion of the societal context and historical developments that have prompted increasing interest in TDSC; (b) a definition and conceptualization of TDSC; (c) a methodological approach for studying TDSC; (d) initial findings from the case study that reflect instances of transdisciplinary intellectual integration and it examines implications of these methods and findings for future research and policy development relevant to substance use and misuse.

Biomedical Research↗
PubMed2003

Should symptoms be scaled for intensity, frequency, or both?

OBJECTIVE: This study evaluated the comparability of two 5-point symptom self-report rating scales: Intensity (from "not at all" to "very much") and Frequency (from "none of the time" to "all of the time"). Questions from the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue 13-item scale was examined. METHODS: Data from 161 patients (60 cancer, 51 stroke, 50 HIV) were calibrated separately to fit an item response theory-based rating scale model (RSM). The RSM specifies intersection parameters (step thresholds) between two adjacent response categories and the item location parameter that reflects the probability that a problem will be endorsed. Along with patient fatigue scores ("measures"), the spread of the step thresholds and between-threshold ranges were examined. The item locations were also examined for differential item functioning. RESULTS: There was no mean raw score difference between intensity and frequency rating scales (37.2 vs. 36.4, p = n.s.). The high correlation (r = .86, p < .001) between the intensity versus frequency scores indicated their essential equivalence. However, frequency step thresholds covered more of the fatigue measurement continuum and were more equidistant, and therefore reduced floor and ceiling effects. SIGNIFICANCE OF RESULTS: These two scaling methods produce essentially equivalent fatigue estimates; it is difficult to justify assessing both. The frequency response scaling may be preferable in that it provides fuller coverage of the fatigue continuum, including slightly better differentiation of people with relatively little fatigue, and a small group of the most fatigued patients. Intensity response scaling offers slightly more precision among the patients with significant fatigue.

Chronic Disease↗
PubMed2003

The integration of electromyography (SEMG) at the workstation: assessment, treatment, and prevention of repetitive strain injury (RSI).

This paper reviews the ergonomic and psychosocial factors that affect musculoskeletal disorders at the workstation. First is a model of a physiological assessment protocol that incorporated SEMG monitoring while working at the computer. Next is a study that showed that participants lack awareness of their muscle tension as compared to the actual SEMG levels. The final study illustrated how an intervention program can reduce RSI symptoms, decrease respiration rate, and lower SEMG activity. Recommendations include suggestions that successful safety and prevention programs need multiple components and that participants should to be trained to control physiological responses with respiration and SEMG biofeedback. All participants should master these physiological skills just as they learn how to use the computer.

Adolescent↗
PubMed2003

Training the transdisciplinary scientist: a general framework applied to tobacco use behavior.

The complexity of public health problems, including the problem of tobacco use behaviors, calls for formal efforts to train transdisciplinary scientists. These scientists can approach problems by using new conceptual frameworks and methodological tools that integrate different disciplinary perspectives. Transdisciplinary training focuses on developing strong scientists with superb core skills while protecting against creating scientists who are "jack of all trades, master of none." Transdisciplinary training is relatively new, with no accepted training model in place. In this paper, we provide a general framework for transdisciplinary training at the advanced graduate and postgraduate levels, with particular reference to tobacco use behaviors. We identify the core attitude, knowledge, and skills competencies that are essential to conducting tobacco use research with a transdisciplinary approach. We outline the structural components of transdisciplinary training that allow for the development of the competencies and discuss what facilitates the transdisciplinary training process. We also discuss the numerous challenges and obstacles to transdisciplinary training. These include the readiness of early-career trainees to undergo transdisciplinary training, professional development risks taken by trainees, administrative and budgetary obstacles inherent in traditional academic institutional structures, and the limited opportunities established scientists have for transitioning their research programs in a transdisciplinary direction. If these obstacles can be overcome, the potential exists for a new generation of transdisciplinary scientists to be trained and be well positioned to make important and unique advances in our understanding of tobacco use and other public health problems.

Career Mobility↗
PubMed2003

Evaluating transdisciplinary science.

The past two decades have seen a growing interest and investment in transdisciplinary research teams and centers. The Transdisciplinary Tobacco Use Research Centers (TTURCs) exemplify large-scale scientific collaborations undertaken for the explicit purpose of promoting novel conceptual and methodological integrations bridging two or more fields. Until recently, few efforts have been made to evaluate the collaborative processes, and the scientific and public policy outcomes, of such centers. This manuscript offers a conceptual framework for understanding and evaluating transdisciplinary science and describes two ongoing evaluation studies covering the initial phase of the TTURC initiative. The methods and measures used by these studies are described, and early evaluative findings from the first 4 years of the initiative are presented. These data reveal progress toward intellectual integration within and between several of the TTURCs, and cumulative changes in the collaborative behaviors and values of participants over the course of the initiative. The data also suggest that different centers may follow alternative pathways toward transdisciplinary integration and highlight certain environmental, organizational, and institutional factors that influence each center's readiness for collaboration. Methodological challenges posed by the complexities of evaluating large-scale scientific collaborations (including those that specifically aspire toward transdisciplinary integrations spanning multiple fields) are discussed. Finally, new directions for future evaluative studies of transdisciplinary scientific collaboration, both within and beyond the field of tobacco science, are described.

Humans↗
PubMed2003

Relationship between body mass and gastro-oesophageal reflux symptoms: The Bristol Helicobacter Project.

OBJECTIVE: To examine the relationship between body mass and gastro-oesophageal reflux in a large population-representative sample from the UK. DESIGN AND SETTING: Cross-sectional population-based study, as part of a randomized controlled trial of eradication of Helicobacter pylori infection, in Southwest England. Subjects In all, 10 537 subjects, aged 20-59 years, were recruited from seven general practices. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken. MAIN OUTCOME MEASURE: Relationship between overweight (body mass index [BMI] >/=25 kg/m(2) and </=30 kg/m(2)) or obesity (BMI >30 kg/m(2)) and frequency and severity of heartburn and acid regurgitation. RESULTS: Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux. The adjusted odds ratios (OR) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 (95% CI: 1.33-2.50) and 1.50 (95% CI: 1.13-1.99) respectively. Corresponding OR (95% CI) relating to obese patients were 2.91 (95% CI: 2.07-4.08) and 2.23 (95% CI: 1.44-3.45) respectively. The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance: OR = 1.19; 95% CI: 1.07-1.33. CONCLUSIONS: Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight.

Adult↗
PubMed2003

Reduced risk of atopic disorders in adults with Helicobacter pylori infection.

BACKGROUND: Childhood infections may be necessary to prime the developing immune system in an appropriate manner. In developed countries, the incidence of childhood infections is decreasing, which might explain the observed rise in the prevalence of asthma and other atopic disorders in recent years. AIM: To determine whether Helicobacter pylori gastritis, a chronic bacterial infection that is usually acquired in early childhood and then persists throughout life, affects the risk of developing asthma and other atopic disorders. STUDY DESIGN: Cross-sectional study of the prevalence of three atopic disorders in 3244 subjects participating in a community-based, prospective, randomized, controlled trial of H. pylori eradication, the Bristol Helicobacter Project. The presence or absence of active H. pylori infection was determined by the 13C-urea breath test. The prevalence of asthma, eczema and allergic rhinitis was measured by assessing the use of appropriate medications as surrogate markers for these conditions. RESULTS: There was a 30% reduction in the prevalence of all three atopic disorders in people who had active H. pylori infection, although for each individual atopic disorder the numbers were not quite large enough to reach statistical significance. CONCLUSIONS: H. pylori infection is associated with a substantially reduced risk of three common atopic disorders. This is further indirect evidence of the importance of childhood infections in influencing the development of a normal immune response. As such infections become progressively less common in developed countries such as the UK, other methods will need to be developed to try to reduce the risk of atopic disorders.

Adult↗
PubMed2002

National survey to assess current practices in the diagnosis and management of young people with dementia.

BACKGROUND: The Royal College of Psychiatrists has recommended that old age psychiatrists may be best placed to take responsibility for service provision for younger people with dementia. There are concerns however, that if referral between specialists, particularly neurologists and old age psychiatrists, is incomplete, patients may be under investigated or inappropriately followed up. OBJECTIVES: We have assessed the current level of referral between these specialists, how each investigates their patients and details of follow up care. METHOD: We conducted a postal survey of all consultant neurologists and consultant old age psychiatrists in the UK with an overall response rate of 64%. RESULTS AND CONCLUSIONS: The ideal of full collaboration between old age psychiatrists and neurologists is not achieved. Young patients may be under investigated if managed solely by an old age psychiatrist and may not receive adequate follow up services if managed solely by a neurologist.

Adult↗