Greening the United Nations' Human Development Index?

The Human Development Index (HDI) introduced by the United Nations Development Programme (UNDP) in 1990 has helped facilitate widespread debate amongst development researchers, practitioners and policy makers. The HDI is an aggregate index, calculated on an annual basis by the UNDP and published in its Human Development Reports, comprising measures of three components deemed by them to be central to development: W income (the gross domestic product per capita), (ii) education (adult literacy rate) and (iii) health (life expectancy at birth). The results of calculating the HDI are typically presented as country/regional league tables, and provide a quick means for policy makers and others to judge performance. Perhaps partly because of the relative simplicity of the index, the HDI has managed to achieve a level of acceptance and use amongst politicians and policy makers that has yet to emerge with any indicator of sustainability. Indeed, despite its existence for 11 years, including nine years after the Rio Earth Summit, the HDI has not even been modified to take on board wider issues of sustainability. This paper will critically examine the potential for 'greening' the HDI so as to include environmental and resource-consumption dimensions. Copyright (C) 2003 John Wiley & Sons, Ltd and ERP Environment.

The Acute Care Undergraduate TEaching (ACUTE) initiative: consensus development of core competencies in acute care for undergraduates in the United Kingdom

Background: The care of the acutely ill patient in hospital is often sub-optimal. Poor recognition of critical illness combined with a lack of knowledge, failure to appreciate the clinical urgency of a situation, a lack of supervision, failure to seek advice and poor communication have been identified as contributory factors. At present the training of medical students in these important skills is fragmented. The aim of this study was to use consensus techniques to identify the core competencies in the care of acutely ill or arrested adult patients that medical students should possess at the point of graduation. Design: Healthcare professionals were invited to contribute suggestions for competencies to a website as part of a modified Delphi survey. The competency proposals were grouped into themes and rated by a nominal group comprised of physicians, nurses and students from the UK. The nominal group rated the importance of each competency using a 5-point Likert scale. Results: A total of 359 healthcare professionals contributed 2,629 competency suggestions during the Delphi survey. These were reduced to 88 representative themes covering: airway and oxygenation; breathing and ventilation; circulation; confusion and coma; drugs, therapeutics and protocols; clinical examination; monitoring and investigations; team-working, organisation and communication; patient and societal needs; trauma; equipment; pre-hospital care; infection and inflammation. The nominal group identified 71 essential and 16 optional competencies which students should possess at the point of graduation. Conclusions: We propose these competencies form a core set for undergraduate training in resuscitation and acute care.

Lymph heart in chick - somitic origin, development and embryonic oedema

The lymph heart is a sac-like structure on either side of avian tail. In some adult birds, it empties the lymph from the copulatory organ; however, during embryonic development, it is thought to circulate extra-embryonic lymph. Very little is known about the origin, innervation and the cellular changes it undergoes during development. Using immunohistochemistry and gene expression profiling we show that the musculature of the lymph heart is initially composed solely of striated skeletal muscle but later develops an additional layer composed of smooth myofibroblasts. Chick-quail fate-mapping demonstrates that the lymph heart originates from the hypaxial compartments of somites 34-41. The embryonic lymph heart is transiently innervated by somatic motoneurons with no autonomic input. In comparison to body muscles, the lymph heart has different sensitivity to neuromuscular junction blockers (sensitive only to decamethonium). Furthermore, its abundant bungarotoxin-positive acetylcholinesterase receptors are unique as they completely lack specific acetylcholinesterase activity. Several lines of evidence suggest that the lymph heart may possess an intrinsic pacing mechanism. Finally, we assessed the function of the lymph heart during embryogenesis and demonstrate that it is responsible for preventing embryonic oedema in birds, a role previously thought to be played by body skeletal muscle contractions.

Rate-limiting steps in the development of atherosclerosis: the response-to-influx theory

A large number of processes are involved in the pathogenesis of atherosclerosis but it is unclear which of them play a rate-limiting role. One way of resolving this problem is to investigate the highly non-uniform distribution of disease within the arterial system; critical steps in lesion development should be revealed by identifying arterial properties that differ between susceptible and protected sites. Although the localisation of atherosclerotic lesions has been investigated intensively over much of the 20th century, this review argues that the factor determining the distribution of human disease has only recently been identified. Recognition that the distribution changes with age has, for the first time, allowed it to be explained by variation in transport properties of the arterial wall; hitherto, this view could only be applied to experimental atherosclerosis in animals. The newly discovered transport variations which appear to play a critical role in the development of adult disease have underlying mechanisms that differ from those elucidated for the transport variations relevant to experimental atherosclerosis: they depend on endogenous NO synthesis and on blood flow. Manipulation of transport properties might have therapeutic potential. Copyright (C) 2004 S. Karger AG, Basel.

Inhibition of E2F abrogates the development of cardiac myocyte hypertrophy

Growth of the post- natal mammalian heart occurs primarily by cardiac myocyte hypertrophy. Previously, we and others have shown that a partial re- activation of the cell cycle machinery occurs in myocytes undergoing hypertrophy such that cells progress through the G(1)/ S transition. In this study, we have examined the regulation of the E2F family of transcription factors that are crucial for the G(1)/ S phase transition during normal cardiac development and the development of myocyte hypertrophy in the rat. Thus, mRNA and protein levels of E2F- 1, 3, and 4 and DP- 1 and DP- 2 were down- regulated during development to undetectable levels in adult myocytes. Interestingly, E2F- 5 protein levels were substantially up- regulated during development. In contrast, an induction of E2F- 1, 3, and 4 and the DP- 1 protein was observed during the development of myocyte hypertrophy in neonatal myocytes treated with serum or phenylephrine, whereas the protein levels of E2F- 5 were decreased with serum stimulation. E2F activity, as measured by a cyclin E promoter luciferase assay and E2F- DNA binding activity, increased significantly during the development of hypertrophy with serum and phenylephrine compared with non- stimulated cells. Inhibiting E2F activity with a specific peptide that blocks E2F- DP heterodimerization prevented the induction of hypertrophic markers ( atrial natriuretic factor and brain natriuretic peptide) in response to serum and phenylephrine, reduced the increase in myocyte size, and inhibited protein synthesis in stimulated cells. Thus, we have shown that the inhibition of E2F function prevents the development of hypertrophy. Targeting E2F function might be a useful approach for treating diseases that cause pathophysiological hypertrophic growth.

Gender differences in early accommodation and vergence development

A remote haploscopic photorefractor was used to assess objective binocular vergence and accommodation responses in 157 full-term healthy infants aged 1-6 months while fixating a brightly coloured target moving between fixation distances at 2, 1, 0.5 and 0.33 m. Vergence and accommodation response gain matured rapidly from 'flat' neonatal responses at an intercept of approximately 2 dioptres (D) for accommodation and 2.5 metre angles(MA) for vergence, reaching adult-like values at 4 months. Vergence gain was marginally higher in females (p = 0.064), but accommodation gain (p = 0.034) was higher and accommodative intercept closer to zero (p = 0.004) in males in the first 3 months as they relaxed accommodation more appropriately for distant targets. More females showed flat accommodation responses (p = 0.029). More males behaved hypermetropically in the first two months of life, but when these hypermetropic infants were excluded from the analysis, the gender difference remained. Gender differences disappeared after three months. Data showed variable responses and infants could behave appropriately and simultaneously on both, neither or only one measure at all ages. If accommodation was appropriate (gain between 0.7 and 1.3; r(2) > 0.7) but vergence was not, males over- and under-converged equally, while the females who accommodated appropriately were more likely to overconverge (p = 0.008). The apparent earlier maturity of the male accommodative responses may be due to refractive error differences but could also reflect gender-specific male preference for blur cues while females show earlier preference for disparity, which may underpin the earlier emerging, disparity dependent, stereopsis and full vergence found in females in other studies.

The development of convergence and accommodation

Aim: To review current literature on the development of convergence and accommodation. The accommodation and vergence systems provide the foundation upon which bifoveal binocular single vision develops. Deviations from their normal development not only are implicated in the aetiology of convergence anomalies, accommodative anomalies and strabismus, but may also be implicated in failure of the emmetropisation process. Method: This review considers the problems of researching the development of accommodation and vergence in infants and how infant research has had to differ from adult methods. It then reviews and discusses the implications of current research into the development of both systems and their linkages. Results: Vergence and accommodation develop rapidly in the first months of life, with accommodation changing from relatively fixed myopic focus in the neonatal period to adult-like responses by 4 months of age. Vergence develops gradually and becomes more accurate after 4 months of age, but has been demonstrated in infants well before the age that binocular disparity detection mechanisms are thought to develop. Hypotheses for this early vergence mechanism are discussed. The relationship between accommodation and vergence shows much more variability in infants than adult literature has found, but this apparent adult/infant difference may be partly attributed to methodological differences rather than maturational change alone. Conclusions: Variability and flexibility characterise infant responses. This variability may enable infants to develop a flexible and robust binocular system for later life. Studies of infant visual cue use may give clues to the aetiology of strabismus and refractive error.

Cell cycle profiles and expression of p21CIP1 and P27KIP1 during myocyte development

The ability of the cardiac myocyte to divide ceases shortly after birth. Thus, following severe injury, e.g., during myocardial infarction, the mature heart is unable to regenerate new tissue to replace the dead or damaged tissue. The identification of the molecules controlling the cessation of myocyte cell division may lead to therapeutic strategies which aim to re-populate the damaged myocardial area. Hence, we have determined the cell cycle profile, expressions and activities of the cyclin-dependent kinase inhibitors (CDKIs), p21CIP1 and p27KIP1, during rat ventricular myocyte development. Fluorescent activated cell sorting (FACS) analyses showed the percentage of S phase myocytes to be decreased significantly throughout development, concomitant with a significant increase in the percentage of G0/G1 and G2/M phase cells. The expression of p21CIP1 and p27KIP1 increased significantly throughout cardiac development and complexed differentially with a number of cyclins and CDKs. Furthermore, an adult myocyte extract reduced neonatal myocyte CDK2 kinase activity significantly (>30%, p<0.05) whereas immunodepletion of p21CIP1 from adult lysates restored CDK2 kinase activity. Thus, p21CIP1 and p27KIP1 may be important for the withdrawal of cardiac myocytes from the cell cycle and for maintaining the G0/G1 and G2/M phase blockades.

Role of G1 phase cyclins and cyclin dependent kinases during hypertrophic growth of adult rat cardiomyocytes

Cell cycle regulatory molecules are implicated in cardiomyocyte hypertrophy. We have investigated protein expression of cyclins A, D1–3, and E and cyclin-dependent kinases (CDKs) 2, 4, 5, and 6 in left ventricular (LV) tissues during the development of LV hypertrophy in rats following aortic constriction (AC). Compared with their expression in sham-operated controls (SH), expression of cyclins D2 and D3 and of CDK4 and CDK6 increased significantly fromday 3 to day 21 after AC concomitant with increased LV mass. However, no significant difference was observed for CDK2 or CDK5. Cyclins A, D1, and E were undetectable. In vitro kinase activities of CDK4 and CDK6 increased ∼70% from day 7 to day 14 in AC myocytes compared with SH myocytes (P< 0.03). Fluorescence-activated cell sorter analysis revealed a G0/G1to G2/M phase progression in AC myocyte nuclei (22.0 ± 1.1% in G2/M) by day 7 postoperation compared with progression in SH myocyte nuclei (14.0 ± 0.8% in G2/M;P < 0.01). Thus an upregulation of certain cell cycle regulators is associated with cardiomyocyte hypertrophy.

Cardiac Na+/H+ exchanger during post-natal development in the rat: Changes in mRNA expression and sarcolemmal activity

We examined Na+–H+exchanger isoform 1 (NHE-1) mRNA expression in ventricular myocardium and its correlation with sarcolemmal NHE activity in isolated ventricular myocytes, during postnatal development in the rat. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA did not change in ventricular myocardium between 2 and 42 days after birth. Therefore, at seven time points within that age range, GAPDH expression was used to normalize NHE-1 mRNA levels, as determined by reverse transcription polymerase chain reaction analysis. There was a progressive five-fold reduction in NHE-1 mRNA expression in ventricular myocardium from 2 days to 42 days of age. As an index of NHE activity, acid efflux rates (JH) were determined in single neonatal (2–4-day-old) and adult (42-day-old) ventricular myocytes (n=16/group) loaded with the pH fluoroprobe carboxy-seminaphthorhodafluor-1. In HEPES-buffered medium, basal intracellular pH (pHi) was similar at 7.28±0.02 in neonatal and 7.31±0.02 in adult myocytes, but intrinsic buffering power was lower in the former age group. The rate at which pHirecovered from a similar acid load was significantly greater in neonatal than in adult myocytes (0.36±0.07v0.16±0.02 pH units/min at pHi=6.8). This was reflected by a significantly greaterJH(22±4v9±1 pmol/cm2/s at pHi=6.8), indicating greater sarcolemmal NHE activity in neonatal myocytes. The concomitant reductions in tissue NHE-1 mRNA expression and sarcolemmal NHE activity suggest that myocardial NHE-1 is subject to regulation at the mRNA level during postnatal development.

Adult skeletal muscle stem cell migration is mediated by a blebbing/amoeboid mechanism

Adult skeletal muscle possesses a resident stem cell population called satellite cells which are responsible for tissue repair following damage. Satellite cell migration is crucial in promoting rapid tissue regeneration but is a poorly understood process. Furthermore, the mechanisms facilitating satellite cell movement have yet to be elucidated. Here the process of satellite cell migration has been investigated revealing that they undergo two distinct phases of movement; firstly under the basal lamina and then rapidly increasing their velocity when on the myofibre surface. Most significantly we show that satellite cells move using a highly dynamic blebbing based mechanism and not via lamellopodia mediated propulsion. We show that nitric oxide and non-canonical Wnt signalling pathways are necessary for regulating the formation of blebs and the migration of satellite cells. In summary, we propose that the formation of blebs and their necessity for satellite cell migration has significant implications in the future development of therapeutic regimes aimed at promoting skeletal muscle regeneration.

A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.