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C Ferrell

Publications and source records attributed to C Ferrell.

9 recordsLinked to original sources

Natural experiments: an underused tool for public health?

Policymakers and public health researchers alike have demanded better evidence of the effects of interventions on health inequalities. These calls have been repeated most recently in the UK in the final Wanless report, which spoke of the "almost complete lack of an evidence base on the cost-effectiveness of public health interventions", and pointed more generally to the limited evidence base for public health policy and practice. Wanless and others have suggested that the gaps may be partially filled by exploiting the opportunities offered by "natural experiments", such as changes in employment opportunities, housing provision, or cigarette pricing. Natural experiments have an important contributions to make within the health inequalities agenda. First, they can play an important role in investigating the determinants of health inequalities. Second, they can assist in the identification of effective interventions, an area where it is widely acknowledged that the evidence-base is currently sparsely populated. This paper discusses some of the benefits and limitations of using this type of evidence, drawing on two ongoing quasi-experimental studies as examples.

Cost-Benefit Analysis↗

Absence of germline infection in male mice following intraventricular injection of adenovirus.

The possibility of inadvertent exposure of gonadal tissue to gene therapy vectors has raised safety concerns about germline infection. We show here that the receptor for coxsackie B viruses and adenoviruses 2 and 5 (CXADR) is expressed in mouse germ cells, suggesting the possibility that these viruses could infect germ cells. To directly assess the risk of germline infection in vivo, we injected an adenovirus carrying the germ-cell-specific protamine promoter fused to the bacterial lacZ reporter gene into the left ventricular cavity of mice and then monitored expression of the reporter gene in germ cells. To differentiate between infection of stem cells and differentiating spermatogenic cells, we analyzed expression of the reporter cassette at different times after viral delivery. Under all conditions tested, mice did not express the Escherichia coli beta-galactosidase protein in developing spermatids or in mature epididymal spermatozoa. Primary germ cells cultured in vitro were also refractory to adenoviral infection. Our data suggest that the chance of vertical germline transmission and insertional mutagenesis is highly unlikely following intracoronary adenoviral delivery.

Adenoviridae↗

The treatment of childhood social anxiety disorder.

The concept of shyness in young children is not new; however, only recently has it been recognized that childhood SAD is a prevalent and severe disorder, with both immediate and long-term implications for academic, social, and emotional functioning. With the recognition that this disorder can result in severe lifetime impairment, both pharmacologic and psychosocial interventions for youth with social phobia are now beginning to be developed, and their efficacy, to be determined. The study of efficacious pharmacologic treatments with childhood anxiety disorders is limited at this time. There has been even less research regarding pharmacotherapy samples of children with childhood social phobia or social anxiety only. Only seven clinical trials have been conducted, and among those, only three were placebo-controlled, double-blind studies. In all of the open-labeled trials, anxious children showed improvement on both SSRIs and benzodiazepines; however, two of the three double-blind studies were unable to replicate these treatment benefits compared with placebo. The inability to find treatment effects may be a manifestation of the small sample sizes used and the comorbidity of the samples used to date. Further examination of the SSRIs and benzodiazepines with placebo-controlled studies is needed to provide more conclusive support for the efficacy of pharmacologic treatment. Similar to pharmacologic studies, research has begun to accumulate that sheds light on effective psychosocial interventions for childhood social phobia. Future research investigating the relative contribution of specific treatment components will allow for greater efficiency in the delivery of these services. Currently, which components are necessary or sufficient is unknown, although, based on meta-analyses conducted with adult outcome studies, exposure in some form seems to be the key ingredient. In addition, little attention has been given to developmental considerations regarding understanding the utility of specific psychosocial treatment components. For example, Spence et al reported that younger socially phobic children (aged 7-9 years) experienced difficulty in understanding the concept of "cognitive challenging," thus necessitating a reduction of this treatment component for this group. In addition, because differences in treatment effects across age groups was not reported, is it unclear whether the addition of a cognitive challenging component is even warranted. Similarly, Beidel et al reported significant improvement rates without the inclusion of a specific cognitive restructuring component. Thus, future research is needed to clarify the exact utility of including this intervention in treatment. Investigations have begun to accumulate that focus solely on the treatment of childhood social phobia, as opposed to general anxiety symptoms. As a result, preliminary evidence supports the use of pharmacologic and psychosocial treatments. Nonetheless, further research is needed to provide a better understanding of the efficacy of different interventions and, in the case of psychosocial treatments, different treatment components for socially phobic children across different developmental periods. Moreover, controlled treatment outcome studies that include specific measures of social anxiety and functioning, in addition to DSM diagnostic criteria, should provide a better (i.e., more thorough) evaluation of specific treatment effects for socially phobic children and adolescents.

Adolescent↗

Endogenous and exogenous Na-K-Cl cotransporter expression in a low K-resistant mutant MDCK cell line.

A low K-resistant mutant Madin-Darby canine kidney (MDCK) cell line, LK-C1, has been shown previously to lack functional Na-K-Cl cotransporter (NKCC) activity, indicating that it may be a useful NKCC "knockout" cell line for structure-function studies. Using immunological probes, we first characterized the defect in the endogenous NKCC protein of the LK-C1 cells and then fully restored NKCC activity in these cells by stably expressing the human secretory NKCC1 protein (hNKCC1). The endogenous NKCC protein of the LK-C1 cells was expressed at significantly lower levels than in wild-type MDCK cells and was not properly glycosylated. This latter finding indicated that the lack of functional NKCC activity in the LK-C1 cells may be due to the inability to process the protein to the plasma membrane. In contrast, exogenously expressed hNKCC1 protein was properly processed and fully functional at the plasma membrane. Significantly, the exogenous hNKCC1 protein was regulated in a manner similar to the protein in native secretory cells as it was robustly activated by cell shrinkage, calyculin A, and low-Cl incubation. Furthermore, when the LK-C1 cells formed an epithelium on permeable supports, the exogenous hNKCC1 protein was properly polarized and functional at the basolateral membrane. The low levels of endogenous NKCC protein expression, the absence of any endogenous NKCC transport activity, and the ability to form a polarized epithelium indicate that the LK-C1 cells offer an excellent expression system with which to study the molecular physiology of the cation Cl cotransporters.

Animals↗

Improving the quality of spirometry in an epidemiological study: The Renfrew-Paisley (Midspan) family study.

Population studies in Britain and elsewhere report deficiencies in quality of pulmonary function measurements. Methods were tested to improve the standardisation of spirometry in an epidemiological study. The spirometer provided visual feedback about acceptability and reproducibility to American Thoracic Society (ATS) standards. After 14 weeks technicians (research nurses) were given feedback and further training. Measurements were repeated in a 5% sample. Participant characteristics and technical factors (technician and technician feedback) predicted unacceptable forced expiratory volume in 1 second (FEV1) and excessively variable FEV1 and forced vital capacity (FVC). Only participant characteristics predicted unacceptable FVC. Feedback to technicians reduced test failure for FEV1 by half and excessive within-session variability by one-third. In the reproducibility study, coefficients of variation for FEV1 and FVC were 3%. Epidemiological studies can achieve standards of between-session reproducibility for spirometry comparable to levels reported by pulmonary function laboratories. Performance feedback to technicians improves the level of minimally acceptable spirometry, and within-session reproducibility.

Adult↗

Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study.

OBJECTIVE: To investigate the association between birth weight of offspring and mortality among fathers and mothers in the west of Scotland. DESIGN: Prospective observational study. PARTICIPANTS: 794 married couples in Renfrew district of the west of Scotland. MAIN OUTCOME MEASURES: Mortality from all causes and from cardiovascular disease over 15 year follow up. RESULTS: Women who had heavier babies were taller, had higher body mass index and better lung function, and were less likely to be smokers than mothers of lighter babies. Fathers of heavier babies were taller and less likely to be smokers than fathers of lighter babies. Mortality was inversely related to offspring's birth weight for both mothers (relative rate for a 1 kg lower birth weight 1.82 (95% confidence interval 1.23 to 2.70)) and fathers (relative rate 1.35 (1.03 to 1.79)). For mortality from cardiovascular disease, inverse associations were seen for mothers (2.00 (1.18 to 3.33)) and fathers (1.52 (1.03 to 2.17)). Adjustment for blood pressure, plasma cholesterol, body mass index, height, social class, area based deprivation category, smoking, lung function, angina, bronchitis, and electrocardiographic evidence of ischaemia had little effect on these risk estimates, although levels of statistical significance were reduced. CONCLUSIONS: Birth weight of offspring was related inversely to mortality, from all causes and cardiovascular disease, in this cohort. The strength of this association was greater than would have been expected by the degree of concordance of birth weights across generations, but an extensive range of potential confounding factors could not account for the association. Mortality is therefore influenced by a factor related to birth weight that is transmissible across generations.

Birth Weight↗

Caught in the middle.

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Emergency Service, Hospital↗

Effects of immunization of heifers against estradiol on growth, reproductive traits, and carcass characteristics.

An experiment was performed to evaluate the effects of active immunization of heifers against estradiol on feedlot performance (growth and efficiency), carcass characteristics, and reproductive functions. Seventy-two crossbred heifers were divided into four equal treatment groups consisting of controls, ovariectomized heifers, and heifers actively immunized against keyhole limpet-estradiol antigen and bovine serum albumin-estradiol antigen. Heifers were fed ad libitum for 170 days. Both groups of heifers immunized against estradiol had higher (P less than 0.05) average daily gains than controls. Heifers immunized against bovine serum albumin-estradiol had increased feed efficiency (P less than 0.05) over controls. Ovariectomized heifers did not perform at levels sufficient to compensate for the initial setback from surgery. No differences were noted in carcass grade, quality, or concentration of water, fat, or protein. Uterine weights were increased in estrogen-immunized animals but were not significantly greater than controls. Ovarian weights and numbers of large follicles (greater than 9 mm diam) in immunized animals were significantly greater than in controls. Twenty-eight percent of the animals (n = 5) in the bovine serum albumin-estradiol-immunized group had cystic follicles (greater than 20 mm diam) and 50% (n = 9) of this group had no detectable corpus luteum. Low titer (1:100) systemic binding of estrogens may act as a steroid reservoir in which systemic estrogen clearance is decreased and availability to target tissues is increased.

Animals↗