Explaining trends in alcohol-related harms in Scotland, 1991-2011 (I): the role of incomes, effects of socio-economic and political adversity and demographic change.

OBJECTIVE: This paper tests the extent to which differing trends in income, demographic change and the consequences of an earlier period of social, economic and political change might explain differences in the magnitude and trends in alcohol-related mortality between 1991 and 2011 in Scotland compared to England & Wales (E&W). STUDY DESIGN: Comparative time trend analyses and arithmetic modelling. METHODS: Three approaches were utilised to compare Scotland with E&W: 1. We modelled the impact of changes in income on alcohol-related deaths between 1991-2001 and 2001-2011 by applying plausible assumptions of the effect size through an arithmetic model. 2. We used contour plots, graphical exploration of age-period-cohort interactions and calculation of Intrinsic Estimator coefficients to investigate the effect of earlier exposure to social, economic and political adversity on alcohol-related mortality. 3. We recalculated the trends in alcohol-related deaths using the white population only to make a crude approximation of the maximal impact of changes in ethnic diversity. RESULTS: Real incomes increased during the 1990s but declined from around 2004 in the poorest 30% of the population of Great Britain. The decline in incomes for the poorest decile, the proportion of the population in the most deprived decile, and the inequality in alcohol-related deaths, were all greater in Scotland than in E&W. The model predicted less of the observed rise in Scotland (18% of the rise in men and 29% of the rise in women) than that in E&W (where 60% and 68% of the rise in men and women respectively was explained). One-third of the decline observed in alcohol-related mortality in Scottish men between 2001 and 2011 was predicted by the model, and the model was broadly consistent with the observed trends in E&W and amongst women in Scotland. An age-period interaction in alcohol-related mortality was evident for men and women during the 1990s and 2000s who were aged 40-70 years and who experienced rapidly increasing alcohol-related mortality rates. Ethnicity is unlikely to be important in explaining the trends or differences between Scotland and E&W. CONCLUSIONS: The decline in alcohol-related mortality in Scotland since the early 2000s and the differing trend to E&W were partly described by a model predicting the impact of declining incomes. Lagged effects from historical social, economic and political change remain plausible from the available data.

Explaining trends in alcohol-related harms in Scotland 1991-2011 (II): policy, social norms, the alcohol market, clinical changes and a synthesis.

OBJECTIVE: To provide a basis for evaluating post-2007 alcohol policy in Scotland, this paper tests the extent to which pre-2007 policy, the alcohol market, culture or clinical changes might explain differences in the magnitude and trends in alcohol-related mortality outcomes in Scotland compared to England & Wales (E&W). STUDY DESIGN: Rapid literature reviews, descriptive analysis of routine data and narrative synthesis. METHODS: We assessed the impact of pre-2007 Scottish policy and policy in the comparison areas in relation to the literature on effective alcohol policy. Rapid literature reviews were conducted to assess cultural changes and the potential role of substitution effects between alcohol and illicit drugs. The availability of alcohol was assessed by examining the trends in the number of alcohol outlets over time. The impact of clinical changes was assessed in consultation with key informants. The impact of all the identified factors were then summarised and synthesised narratively. RESULTS: The companion paper showed that part of the rise and fall in alcohol-related mortality in Scotland, and part of the differing trend to E&W, were predicted by a model linking income trends and alcohol-related mortality. Lagged effects from historical deindustrialisation and socio-economic changes exposures also remain plausible from the available data. This paper shows that policy differences or changes prior to 2007 are unlikely to have been important in explaining the trends. There is some evidence that aspects of alcohol culture in Scotland may be different (more concentrated and home drinking) but it seems unlikely that this has been an important driver of the trends or the differences with E&W other than through interaction with changing incomes and lagged socio-economic effects. Substitution effects with illicit drugs and clinical changes are unlikely to have substantially changed alcohol-related harms: however, the increase in alcohol availability across the UK is likely to partly explain the rise in alcohol-related mortality during the 1990s. CONCLUSIONS: Future policy should ensure that alcohol affordability and availability, as well as socio-economic inequality, are reduced, in order to maintain downward trends in alcohol-related mortality in Scotland.

Severe hemolytic disease of the newborn from anti-e.

Maternal antibody-mediated fetal red blood cell destruction secondary to non-D Rhesus (Rh) antibodies is a significant cause of hemolytic disease of the newborn (HDN). Here, we report a rare case of severe HDN associated with maternal antibody to Rh e. In addition to severe anemia, the infant developed thrombocytopenia, conjugated hyperbilirubinemia and cholelithiasis. Resolution of the infant's cholelithiasis occurred following treatment with ursodeoxycholic acid.

Long-distance air medical transport of extremely low birth weight infants with pneumoperitoneum.

OBJECTIVE: Long-distance air transport (LDAT) of infants with pneumoperitoneum for pediatric surgical evaluation has not been previously reported. We examined whether extremely low birth weight (ELBW) infants with and without pneumoperitoneum would tolerate transport differently. STUDY DESIGN: A retrospective cohort study was conducted comparing ELBW infants diagnosed with pneumoperitoneum to other ELBW infants transported>2000 miles by a trained team from a US Department of Defense tertiary care neonatal intensive care unit in Okinawa, Japan. RESULT: Between 2000 and 2006, 49 air transports met study criteria. Seven of the 49 (14%) infants had pneumoperitoneum at time of transport. The average distance flown was 5346 miles per transport. The 49 infants had a median gestational age of 25 weeks and birth weight of 761+/-127 g. ELBW infants without pneumoperitoneum were transported at a median 58 days of life (DOL; range 30 to 91 days) compared to infants with pneumoperitoneum, who were transported at a median 8 DOL (range 6 to 14 days). At the time of LDAT, infants with pneumoperitoneum were significantly smaller, receiving more arterial and central venous access, more pressors for hypotension, and more mechanical ventilation compared to ELBW infants transported without pneumoperitoneum. In-flight patient-related medical issues were similar regardless of underlying diagnosis or age at the time of transport. CONCLUSION: Successful LDAT of ELBW infants, including critically ill infants with intestinal perforation, is possible. Use of personnel, experienced and trained in aviation transport physiology, overcomes the extreme physiologic operating environment associated with LDATs.

Placental transfusion: a review.

Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution.

The effect of age on the sensitivity of pre- and postsynaptic alpha-adrenoceptors to agonists and antagonists in the rat.

Age-related changes in presynaptic alpha-2 and postsynaptic alpha-1 adrenoceptors have been determined using the rat isolated vas deferens and the thoracic aorta, respectively. The IC50 values of clonidine, B-HT 933 and UK 14,304 for inhibition of the electrically evoked contractions of the vas deferens were significantly higher in 50 week old rats when compared with rats of 5 weeks. Similarly, EC50 values for the contraction of the thoracic aorta by noradrenaline, methoxamine and phenylephrine were significantly increased in 50 week old rats compared with 5 week old rats. No age-related changes in the potency of the selective alpha-2 adrenoceptor antagonists yohimbine and Wy 26392 were detected in the vas deferens. Similarly, there were no age-related changes in the alpha-1 adrenoceptor antagonist potency of indoramin or prazosin on the aorta. The results of the present study suggest that the potency of both alpha-1 and alpha-2 adrenoceptor agonists, as measured by their respective EC and IC50 values decreases with increasing age.

Some pharmacological properties of Wy 27127 a more selective alpha 2:alpha 1-adrenoceptor antagonist than idazoxan in vitro.

Wy 27127 and idazoxan were approximately equipotent as antagonists at alpha 2-adrenoceptors as estimated by their ability to block clonidine-induced inhibition of electrically-evoked contractions of the rat isolated vas deferens. Idazoxan was seven times as potent as Wy 27127, as an antagonist at alpha 1-adrenoceptors as indicated by blockade of methoxamine-induced contractions of the rat isolated anococcygeus muscle. Thus, the alpha 2:alpha 1 selectivity ratio, as calculated from these tests was 407 for Wy 27127 and 76 for idazoxan. Wy 27127 and idazoxan were equipotent in enhancing stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [3H]-noradrenaline as expected for alpha 2-adrenoceptor antagonists. At higher concentrations both compounds reduced the stimulation-evoked contraction of the pulmonary artery but idazoxan was 15 times as potent as Wy 27127 in this respect. Neither compound had marked antagonist actions at 5-hydroxytryptamine (D), muscarinic, presynaptic dopamine or histamine (H1) receptors or at beta 1-adrenoceptors. Thus, idazoxan and Wy 27127 were equipotent alpha 2-adrenoceptor antagonists in vitro, however, the alpha 2:alpha 1 selectivity of Wy 27127 was considerably greater than that of idazoxan by virtue of weaker alpha 1-adrenoceptor antagonism.

Alpha 2-adrenoceptor antagonism and other pharmacological antagonist properties of some substituted benzoquinolizines and yohimbine in vitro.

Comparison of pA2 values for antagonism of clonidine induced inhibition of the electrically evoked contraction of the rat isolated vas deferens (alpha 2-adrenoceptor) and antagonism of contractions to methoxamine on the rat isolated anococcygeus (alpha 1-adrenoceptor) showed a group of substituted benzoquinolizines (Wy 25309, 26392 and 26703) to be more potent and more selective alpha 2-adrenoceptor antagonists than yohimbine. The benzoquinolizines and yohimbine enhanced stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [3H]-noradrenaline, as expected for alpha 2-adrenoceptor antagonists. In contrast to the results on the rat vas deferens, yohimbine was more potent than the benzoquinolizines. At higher concentrations all the alpha-adrenoceptor antagonists reduced the stimulation-evoked contraction of the pulmonary artery. The benzoquinolizines were competitive antagonists of 5-hydroxytryptamine on the rat isolated ileum. Wy 25309 showed only weak activity (pA2 = 5.21) whereas Wy 26703 was more potent (pA2 = 7.25). Yohimbine was a potent antagonist of 5-hydroxytryptamine. Wy 26703 was the only compound to have histamine antagonist effects in the guinea pig isolated ileum and to antagonise the chronotropic effect of isoprenaline on the isolated atria of the guinea pig and in both instances activity was weak (pA2 values 5.3 and 5.5 respectively). Yohimbine reduced the spontaneous beating of the atria at 3 X 10(-6) M. No compound at 10(-5) M antagonised acetylcholine on the guinea pig ileum. These novel substituted benzoquinolizines should be useful experimental compounds for the study of alpha 2-adrenoceptor mediated responses.

The effect of temperature on the alpha-adrenoceptor antagonist potency of indoramin and labetalol in the rat perfused mesenteric vascular bed.

The effect of reduction in temperature of perfusion from 37 to 27 degrees C and 20 degrees C on the ability of the adrenoceptor antagonists indoramin and labetalol to block pressor responses to noradrenaline in the perfused mesenteric vascular bed of the rat was examined. The results suggest that in rat mesenteric bed, antagonist potency of both agents is increased at low temperatures.

What we say and what we do: county-level public spending for health care.

The purpose of this study is to examine county-level public spending for health care services in Kansas and to explain variation in spending levels with a model composed of population density, population age and per capita income. Data are abstracted from budget documents for all 105 counties in Kansas for the years 1994, 1995 and 1996. Health care expenditures are defined as county tax revenues spent for ambulance, hospitals, ambulatory care, home health services, nursing homes, and mental health and substance abuse services. Results show that Kansas counties spent between 12.1 percent and 13.6 percent of their budgets to fund local health care services between 1994 and 1996, spending more than $133 million in 1996 alone. In 10 counties, one-quarter to one-third of the budget went for health services. Low population density and relatively high per capita income explained nearly one-third of the variation in how much counties spent and an even greater proportion when analysis was limited to the most rural counties. Findings from this study suggest there may be a significant local commitment in the United States to publicly supported health care services, more support than typically recognized and perhaps more than is estimated in national health care spending data. Future research on the economic effects of the health sector on local communities should take account of local spending for health care, especially at the county level.

How to defuse compliance time bombs. Part 2: Six hypothetical allegations. Panel discussion.

In the second and final part of this series, a panel of legal experts discusses more hypothetical allegations against a fictional laboratory, including billing for additional indices, using expired reagents, and falsifying the results of employee competency tests. Learn how to handle these dilemmas before they explode into full-blown legal violations.

Beyond ITER: neutral beams for a demonstration fusion reactor (DEMO) (invited).

In the development of magnetically confined fusion as an economically sustainable power source, International Tokamak Experimental Reactor (ITER) is currently under construction. Beyond ITER is the demonstration fusion reactor (DEMO) programme in which the physics and engineering aspects of a future fusion power plant will be demonstrated. DEMO will produce net electrical power. The DEMO programme will be outlined and the role of neutral beams for heating and current drive will be described. In particular, the importance of the efficiency of neutral beam systems in terms of injected neutral beam power compared to wallplug power will be discussed. Options for improving this efficiency including advanced neutralisers and energy recovery are discussed.

Novel NKX2.1 mutation associated with hypothyroidism and lethal respiratory failure in a full-term neonate.

We report a case of lethal neonatal hypoxic respiratory failure and hypothyroidism in an infant with a novel missense mutation in NKX2.1.

Outcomes of extremely low birth weight infants given early high-dose erythropoietin.

OBJECTIVE: To evaluate long-term outcomes of 60 extremely low birth weight (ELBW) infants treated with or without three injections of high-dose erythropoietin (Epo). STUDY DESIGN: A retrospective analysis of anthropometric and neurodevelopmental outcome data comparing 30 ELBW infants enrolled in a phase I/II study examining the pharmacokinetics of high-dose Epo (500, 1000 and 2500 U/kg × 3 doses) administered to 30 concurrent controls. RESULT: Birth characteristics and growth from 4 to 36 months were similar for untreated and Epo-treated patients. Multiple linear regression analysis of neurodevelopmental follow-up scores from 17/25 Epo-treated and 18/26 control infants identified that Epo correlated with improvement of cognitive (R=0.22, P=0.044) and motor (R=0.15, P=0.026) scores. No negative long-term effects of Epo treatment were evident. CONCLUSION: Retrospective analysis of the only available long-term follow-up data from ELBW infants given high-dose Epo treatment suggests that Epo treatment is safe and correlates with modest improvement of neurodevelopmental outcomes.

Sheath structure in negative ion sources for fusion (invited).

In fusion negative ion sources, the negative ions are formed on the caesiated plasma grid predominantly by hydrogen atoms from the plasma. The space charge of the negative ions leaving the wall is not fully compensated by incoming positive ions and at high enough emission a virtual cathode is formed. This virtual cathode limits the flux of negative ions transported across the sheath to the plasma. A 1D collisionless model of the sheath is presented taking into account the virtual cathode. The model will be applied to examples of the ion source operation. Extension of the model to the bulk plasma shows good agreement with experimental data. A possible role for fast ions is discussed.