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Background: Past research suggests that perceived neighbourhood conditions may influence adolescents' emotional health. Relatively little research has been conducted examining the association of perceived neighbourhood conditions with depressive symptoms among Caribbean adolescents. This project examines the association of perceived neighbourhood conditions with levels of depressive symptoms among adolescents in Jamaica, the Bahamas, St. Kitts and Nevis, and St. Vincent., Methods: Adolescents attending grade ten of the academic year 2006/2007 in Jamaica, the Bahamas, St. Vincent, and St. Kitts and Nevis were administered the Neighbourhood Characteristics Questionnaire along with the BDI-II. Social cohesion, attachment to the neighbourhood, neighbourhood quality, neighbourhood crime, and neighbourhood disorder scales were created by summing the relevant subscales of the Neighbourhood Characteristics Questionnaire. Multiple regression analyses were used to examine the relationships of perceived neighbourhood conditions to depressive symptoms., Results: A wide cross-section of tenth grade students in each nation was sampled (n = 1955; 278 from Jamaica, 217 from the Bahamas, 737 St. Kitts and Nevis, 716 from St. Vincent; 52.1% females, 45.6% males and 2.3% no gender reported; 12 to 19 years, mean = 15.3 yrs, sd = .95 yr). Nearly half (52.1%) of all adolescents reported mild to severe symptoms of depression with 29.1% reporting moderate to severe symptoms of depression. Overall, Jamaican adolescents perceived their neighbourhoods in a more positive manner than those in the Bahamas, St. Vincent and St. Kitts and Nevis. Results of a series of hierarchical multiple regression analyses suggested that a different pattern of neighbourhood factors for each island were associated with depressive symptoms. However, neighbourhood factors were more highly associated with depressive symptoms for Jamaican students than for students in the other three islands., Conclusions: Neighbourhood factors appear to be partially associated with adolescents' self-reports of depressive symptoms. However, other factors may mitigate this relationship.

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor.

A polymer must reach a certain size to exhibit significant excluded-volume interactions and adopt a swollen random-walk configuration. We show that single-molecule measurements can sense the onset of swelling by modulating the effective chain size with force: as the force is reduced from a large value, the polymer is first highly aligned, then a Gaussian coil, then finally a swollen chain, with each regime exhibiting a distinct elasticity. We use this approach to quantify the structural parameters of poly(ethylene glycol) and show that they vary in the expected manner with changes in solvent.

Background: Acute coronary syndrome (ACS) patients treated with inpatient coronary artery bypass graft (CABG) surgery are at significant risk for future Major Adverse Cardiovascular events (MACE). The use of evidence-based medications (aspirin, statins, beta-blockers and angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBS)) can reduce MACE in these patients., Methods: We used a prospective database of all patients admitted to the Green Lane Cardiovascular Service, Coronary Care Unit (CCU) at Auckland City Hospital (ACH). We contacted patients General Practitioners for current patient data including MACE, which was supplemented by using the hospital patient records., Results: From 1/6/2006 to 31/7/2007, 901 patients presented with an ACS; of these 129 received inpatient CABG. 2 patients died before hospital discharge. At a median follow up time of 2.9 [IQR 2.7-3.3] years, 109 (86%) patients were traced and their medication assessed. Only 90 (83%) patients remained on aspirin, 78 (72%) on statins, 67 (62%) on beta-blockers and 47 (43%) on ACE inhibitors/ARBs. From the total of 127 patients discharged from hospital, there were a total of 18 MACE (6.2%/year): 3 unstable angina, 4 non-ST elevation myocardial infarction (NSTEMI), 6 congestive heart failure (CHF) and 5 deaths., Conclusion: Suboptimal use of secondary prevention drugs in high risk ACS patients treated with urgent CABG surgery may contribute to subsequent adverse events. Greater efforts to optimise the use of these medications are needed to improve outcomes.

This article considers the requirements set out in the Mental Capacity Act 2005 for valid advance decisions. The Act recognizes that an adult with capacity may refuse treatment, including life-sustaining treatment, in advance of losing capacity. If that advance decision is valid and applicable, it will bind health-care professionals, taking effect as if the patient had contemporaneously refused the treatment. However, in cases where the advance decision does not relate to treatment for a progressive disease, it will be extremely difficult for the patient to meet the dual specificity requirement - specifying the treatment to be refused and the circumstances in which that refusal should operate. Moreover, while a patient may explicitly revoke an advance decision while she retains the capacity to do so, the continuing validity of an advance decision may be called into question by the patient implicitly revoking her advance refusal or by a change of circumstance. This article concludes that the key to enabling patients to exercise precedent autonomy will be full and frank discussion of the scope and intentions underlying advance decisions between patients and their health-care professionals.

This paper presents empirical data on the prevalence of depressive symptoms among St. Kitts and Nevis adolescent students. This paper contributes to knowledge on the prevalence of adolescent depression in an under-researched Caribbean region.

Ornithine decarboxylase (ODC), the first enzyme in the biosynthesis of polyamines, has increased activity in breast cancer tissue compared with benign and normal tissues. The ODC gene contains a single nucleotide polymorphism in which a guanine is substituted for an adenine. This study investigated whether the ODC +316 G > A polymorphism (rs2302615) was associated with the risk of developing breast cancer. A case-control study involving 121 controls, without breast cancer, 46 patients with breast cancer but without a family history, and 130 breast cancer cases with a family history of breast cancer was conducted. A nested PCR-restriction fragment length polymorphism procedure and the TaqMan 5' nuclease assay was used to genotype individuals. Risk was significantly lower for heterozygote (GA genotype) individuals [odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.17-0.86, P = 0.018], or individuals with at least one A allele (OR = 0.44, 95% CI 0.21-0.92, P = 0.027), without family history. This protective effect of having at least one copy of the variant A allele was not as strong, however, in those with a family history of the disease. In sporadic breast cancer, the presence of at least one A allele is protective against the disease. The influence of this polymorphism may be less important in individuals with an inherited breast cancer predisposition.

At a time when hospital infections are rarely out of the news, it is important to reflect that the origins of midwifery as a profession owe much to the actions of a group of determined women who, in the face of much opposition from within the medical profession, strove to improve upon standards of hygiene in maternity care to reduce the high levels of maternal and infant mortality associated with some of the most prestigious hospitals in the land.

James Currie was born and educated in Scotland but spent most of his professional life in Liverpool, where, as physician to the Liverpool Infirmary, he campaigned against the unsanitary living conditions in the rapidly growing port. He was an early advocate of water cures for fever and other maladies, on which subject he carried out experiments and published a seminal work. He was a pioneer in the use of the clinical thermometer. He was also an early advocate of the abolition of slavery and a man with literary and scientific interests, which brought him into contact with many of his most distinguished contemporaries. These included Erasmus Darwin (1731-1802), William Wilberforce (1759-1833), Sir Walter Scott (1771-1832), Sir Joseph Banks (1743-1820) and Robert Burns (1759-96), of whose poetry Currie was the first editor. He died in August 1805 at Sidmouth in Devon, whose parish church carries his memorial.

Objective: This chapter discusses how to market to and educate the referral community and third party payers about the benefits of the emerging PET/CT technology., Conclusion: Clearly, the fusion of PET and CT into one piece of equipment will present challenges for years to come. It is important for providers to be involved with all of the administrators, managers, referring and interpreting physicians, and the payer communities in their market to clearly understand individual payer business practices and to identify opportunities to educate and influence changes in payment and coverage policies.

The authors evaluated 30 subjects with treated unilateral slipped capital femoral epiphysis and a range of severity from mild to severe to characterize gait and strength abnormalities using instrumented three-dimensional gait analysis and isokinetic muscle testing. For slip angles less than 30 degrees, kinematic, kinetic, and strength variables were not significantly different from age- and weight-matched controls. For moderate to severe slips, as slip angle increased, passive hip flexion, hip abduction, and internal rotation in the flexed and extended positions decreased significantly. Persistent pelvic obliquity, medial lateral trunk sway, and trunk obliquity in stance increased, as did extension, adduction, and external rotation during gait. Gait velocity and step length decreased with increased amount of time spent in double limb stance. Hip abductor moment, hip extension moment, knee flexion moment, and ankle dorsiflexion moment were all decreased on the involved side. Hip and knee strength also decreased with increasing slip severity. All of these changes were present on the affected and to a lesser degree the unaffected side. Body center of mass translation or pelvic obliquity in mid-stance greater than one standard deviation above normal correlated well with the impression of compensated or uncompensated Trendelenburg gait.

Scrapie is a transmissible spongiform encephalopathy in which there is an accumulation of the abnormal form of the prion protein, PrPsc, in the lymphoreticular system and nervous system. There is a particular accumulation of PrPsc on follicular dendritic cells within the germinal centre of B-cell follicles. Because accumulation of PrPsc in the nervous system leads to neuronal cell loss we have examined PrPsc accumulation in the prescapular and mesenteric lymph nodes in relation to lymph node architecture of scrapie-challenged sheep. We demonstrate that an accumulation of PrPsc in the lymph node fails to result in gross defects in the microanatomy and phenotype of T- and B-cell areas in the lymph nodes.

William Henry Duncan (1805-1863) was born in Liverpool, qualified in Edinburgh, then moved back to Liverpool to work in general practice. He became physician to the Liverpool Infirmary and began to campaign for improvements to the appalling living conditions of his patients. He was appointed Liverpool's Medical Officer of Health on 1 January 1847 - Britain's first.

In this study 11 ambulatory patients (mean 10.8 years) with spastic cerebral palsy were each evaluated with instrumented gait analysis at four different centers. After review of the data, each medical director chose from a list of treatment options. The average variability in static range of motion from physical examination ranged from 25 degrees to 50 degrees. Hip and knee sagittal motion had the best relative variability of 20 degrees to 24%. Via gait analysis, the average variability in sagittal, coronal, and transverse plane kinematic motions averaged 12, degrees 7 degrees, and 20 degrees, respectively. Increased variability was noted in transverse (worst) to coronal and finally sagittal (best) plane motion. Only two mildly affected patients had similar, but not exact, treatment recommendations. The authors conclude that substantial variations in raw data exist when the same cerebral palsy patient is evaluated at different gait centers. These data do not yield the same treatment recommendations in the majority of patients.

Poly(1-methyl-6-thioinosinic acid), or PMTI, is a single-stranded polyribonucleotide and is the first homopolyribonucleotide devoid of Watson-Crick hydrogen bonding sites to show potent human immunodeficiency virus (HIV) inhibition. PMTI was found to be active when evaluated against a variety of low passage clinical HIV isolates in fresh human peripheral blood cells, including T cell-tropic and monocyte-macrophage-tropic viruses, syncytium-inducing and non-syncytium-inducing viruses and viruses representative of the various HIV-1 clades (A through F). The compound was active against HIV-2, all nucleoside and non-nucleoside reverse transcriptase (RT) inhibitor drug-resistant virus isolates tested and interacted with AZT or ddl to synergistically inhibit HIV infection. In biochemical inhibition assays, PMTI was determined to be a potent inhibitor of HIV-1 and HIV-2 RT, including RTs with mutations that engender resistance to nucleoside and non-nucleoside RT inhibitors. PMTI inhibited both the polymerase and RNase H activities of HIV RT. PMTI did not inhibit HIV-1 protease or integrase. Cell-based mechanism of action assays indicated that PMTI also interfered with early events in the entry of HIV into target cells. Furthermore, PMTI inhibited the fusion of gp120-expressing and CD4-expressing cells, but at concentrations approximately 1 log10 greater than those that inhibited virus entry. These results suggest that the homopolyribonucleotide PMTI blocks HIV replication in human cells at its earliest stages by multiple mechanisms, inhibition of virus entry and inhibition of RT.

Aqueous extracts of the New Zealand sponge Adocia sp. (Haplosclerida) displayed potent anticytopathic activity in CEM-SS cells infected with HIV-1. Protein fractions of the extract bound both to the viral coat protein gp120 and to the cellular receptor CD4, but not to other tested proteins. The purified active protein, named adociavirin, was characterized by isoelectric focusing, amino acid analysis, MALDI-TOF mass spectrometry and N-terminal sequencing. Adociavirin, a disulfide-linked homodimer with a native molecular weight of 37 kDa, was active against diverse strains and isolates of HIV-1, as well as HIV-2, with EC50 values ranging from 0.4 nM to > 400 nM. The anti-HIV potency of adociavirin appears dependent on host cell type, with macrophage cultures being the most sensitive and peripheral blood lymphocytes the most resistant.

Twelve patients with healed congenital pseudarthrosis of the tibia underwent gait analysis and muscle strength testing to determine the functional result of treatment. Six children younger than 4 years of age presented with pseudarthroses (early onset), and six children first fractured at older than 4 years of age (delayed onset). Four children with amputations as final treatment for congenital pseudarthrosis were studied for comparison. The early-onset group had undergone an average of 4.2 surgeries and all required transankle fixation. The delayed-onset group had undergone an average of 1.5 surgeries, with one child requiring fixation across the ankle. Lack of ankle push-off and foot drop occurred in the early-onset group. Terminal stance phase ankle power generation was greatly diminished in the early-onset group. Total mechanical work performed by the affected limb, when compared to the uninvolved contralateral limb, was symmetric in delayed-onset patients and reduced by 68% in early-onset patients and by 85% in amputees. Gastrocsoleus strength was reduced by 40%. Gait and muscle strength of patients with "healed" congenital pseudarthrosis of the tibia are markedly disturbed. Early onset of disease, early surgery, and transankle fixation lead to an inefficient gait comparable to that of amputees.

We evaluated the gait of thirty-five neurologically normal children who had a limb-length discrepancy of the lower extremities that ranged from 0.8 to 15.8 per cent of the length of the long extremity (0.6 to 11.1 centimeters). The twenty-two boys and thirteen girls had an average age of thirteen years (range, eight to seventeen years). No patient had a substantial angular or rotational deformity of the lower extremities. We found no correlation between the actual discrepancy or the per cent discrepancy and any of the dependent kinematic or kinetic variables, including pelvic obliquity. Discrepancies of less than 3 per cent of the length of the long extremity were not associated with compensatory strategies. When a discrepancy was 5.5 per cent or more, more mechanical work was performed by the long extremity and there was a greater vertical displacement of the center of body mass. Clinically, this degree of discrepancy was manifested by the use of toe-walking as a compensatory strategy. Children who had less of a discrepancy were able to use a combination of compensatory strategies to normalize the mechanical work performed by the lower extremities.

Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development.

The first part of this article focused on the stresses and satisfactions arising out of the performance of the direct care role for staff working in three houses in the community for young people with severe learning disabilities and challenging behaviour. This article focuses on the experience of home/work conflict by staff and the impact of organisational issues in relation to staff-staff and staff-management communication, the processes for decision making and standard setting, operational policies and rotating shifts and their effects on the morale and stress levels of staff.

In this article, the first of two parts, the sources of stress and satisfaction experienced by nursing and social service staff working in group homes with young people with severe learning disabilities are investigated. It focuses on the stresses and satisfactions arising out of the performance of the direct care role for staff working in ordinary housing in the community.

The chronotropic effect of three beta-1-adrenoceptor partial agonists prenalterol, xamoterol and epanolol has been compared on the right atria of the rat in order to evaluate their intrinsic activity and to place them in rank order of effectiveness. The results show that prenalterol, xamoterol and epanolol are all partial agonists. The intrinsic activities relative to that of isoprenaline are 0.84 for prenalterol, 0.59 for xamoterol and 0.29 for epanolol. This rank order of intrinsic activities should remain the same in different species and in man. Both atenolol and propranolol reversed the chronotropic effects of the three agonists. The KB of the two blockers was similar against prenalterol and xamoterol, which indicates that the two partial agonists are probably competing for the same population of receptors. The EC50 is twice as large than KB for xamoterol, which is consistent with isoprenaline working through both beta-1- and beta-2- receptors and xamoterol finds it more difficult to block the beta-2-receptors.

Forty four children with daytime wetting were included in a randomly controlled trial of two alarm devices, a contingent one that sounded when wetting occurred and a non-contingent one that went off from time to time unrelated to wetting events. A quota allocation system ensured comparability between treatment groups. Two thirds responded to an alarm by becoming dry. The non-contingent alarm produced as good a response as the contingent one and is recommended for routine use in children with diurnal enuresis. Twenty three per cent of those who responded to treatment relapsed up to two years after completion of the trial.

We examined the interaction between isoproterenol and erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol (ICI 118,551), a beta-2 selective adrenergic receptor antagonist, with respect to heart rate, diastolic blood pressure and twitch tension (soleus muscle) in anesthetized cats. Dose-response curves to isoproterenol (0.025-1.0 micrograms/kg i.v.) were generated for each parameter and then repeated successively after three doses of ICI 118,551 (10, 25 and 100 micrograms/kg i.v.) ICI 118,551 did not significantly alter isoproterenol-induced changes in heart rate, but effects on diastolic blood pressure and twitch tension were inhibited competitively. The data confirm the beta-2 nature of the skeletal muscle adrenergic receptor and suggest that it may be slightly more sensitive than that in blood vessels. Because depression of twitch tension is known to correlate with essential tremor, the data are consistent with clinical reports demonstrating control of tremor by nonselective beta adrenergic receptor antagonists. ICI 118,551 may be efficacious in controlling tremor in man.

Six groups of four dogs were studied under pentobarbital anesthesia. Plasma levels of free fatty acids (FFA), glucose, insulin and lactate were measured after four challenges with isoproterenol (0.125 micrograms/kg/min i.v. for 10 min). In control animals, infusion of isoproterenol elevated plasma FFA, glucose, insulin and lactate, raised heart rate and lowered diastolic blood pressure. Propranolol lowered resting heart rate and blocked all the isoproterenol-induced responses. Atenolol (beta-1-selective antagonist) slowed resting heart rate and blocked FFA and heart rate responses. ICI 118,551 (beta-2-selective antagonist) blocked the glucose, insulin and lactate responses and the fall in diastolic blood pressure. Selectivity was lost at higher doses. ICI 141,292 (potent beta-1-selective antagonist and modest partial agonist) exhibited beta-1-selective blockade against both cardiovascular (heart rate) and metabolic (FFA) receptors. Partial agonist activity was also beta-1-selective, but there was no evidence of agonist activity at the metabolic receptors.

One hundred and ninety six Asian, 89 African, 96 Chinese and 98 Scottish children from 173 families were studied to assess growth in relation to country of birth, time of parental residence in Scotland, child order in family, social class, living conditions and dietary factors. The growth measurements (standardised height, weight and bone age) differed between ethnic groups. The Africans were the tallest and Scottish the shortest. In all immigrant groups, children born in Scotland were on average, taller and more advanced in bone age than those born in their country of origin. In this study, there was no demonstrable effect on growth of social class or of living conditions. Dietary variable showed a lack of coherent effects on growth.

While specific antagonists of the beta 1-adrenoceptor, such as atenolol and betaxolol, are widely available, a potent specific antagonist selective for the beta 2-adrenoceptor has yet to be described. Previously described beta 2-selective antagonists such as butoxamine, H 35/25, and IPS 339 are lacking in potency, specificity, or appropriate beta 2-selectivity. ICI 118,551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] possesses a high degree of selectivity and specificity for the beta 2-adrenoceptor. The affinity of propranolol and ICI 118,551 for beta-adrenoceptors has been determined by comparing their antagonist potencies, expressed as pA2 values, against the actions of isoproterenol on the guinea pig atrium and uterus. ICI 118,551 had a higher affinity for the uterine beta 2-receptor than did propranolol (pA2 9.26 and 8.64, respectively) but a lower affinity for the atrial beta 1-receptor (pA2 7.17 and 8.30, respectively). Thus, the beta 2/ beta 1-selectivity ratios, in vitro, were 123 for ICI 118,551 and 2.2 for propranolol. The potency and selectivity of ICI 118,551 and atenolol on the chronotropic and vasodilator actions of isoproterenol were compared in anaesthetised dogs. The apparent K' B values at the vascular beta-adrenoceptor were 2.1 micrograms/kg for ICI 118,551 and 253 micrograms/kg for atenolol, and the potency ratio for antagonism of vascular versus atrial actions of isoproterenol was greater than 250:1. In regard to ancillary pharmacological properties, ICI 118,551 has no partial agonist activity but has a membrane-stabilising action similar to that of propranolol.

The interactions between ICI 118, 587 (Corwin) a beta 1-selective partial adrenergic agonist, and atenolol (Tenormin), propranolol (Inderal) and verapamil were examined first in anaesthetised dogs pretreated with syrosingopine and vagotomised. ICI 118, 587 was administered iv in cumulative doses of 0.1 to 1000 micrograms X kg-1. In four animals, heart rate increased from 102 +/- 4 to 188 +/- 12 beats X min-1 with a KA of 2.5 +/- 0.9 micrograms X kg-1. ICI 118, 587 was then administered to five groups each of four animals pretreated with atenolol (250 micrograms X kg-1 and 500 micrograms X kg-1iv), propranolol (250 micrograms X kg-1 and 500 micrograms X kg-1) or verapamil (200 micrograms X kg-1 plus 5 micrograms X kg-1 X min-1 iv). Both atenolol and propranolol shifted the dose response curve to the right but verapamil did not. Atenolol did not lower the maximal heart rate response to ICI 118,587. Both propranolol and verapamil slowed heart rate significantly (P less than 0.05) after, but not before, ICI 118,587. Further studies were then carried out in vitro. Cat papillary muscles were superfused with physiological saline at pH 7.4 and with either atenolol or ICI 118,587 at 5 X 10(-5) mol X litre-1. Tension was recorded at Lmax over a [Ca2+] range of 0.5 to 8 X 10(-3)mol X litre-1. The pA2 for verapamil against Ca2+ in the presence of atenolol and ICI 118,587 was 5.25 +/- 0.10 and 6.57 +/- 0.22 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)