Organising a World Congress of Epidemiology (WCE): reflections and lessons from the XIX WCE, Scotland.

The 3-yearly World Congress of Epidemiology is the premier, international, scientific conference organised under the auspices of the International Epidemiological Association (in open competition). This paper explores the justification for seeking to host the Congress and reflects on the structures and processes adopted in making the XIXth Congress in Scotland happen. Preparing the bid was invaluable for forming collaborations, generating scientific ideas, and garnering opinion. After the bid was accepted, we formed a local organising committee, named the Management Executive Committee to signal its decision making authority; and scientific, fundraising, marketing, international and social subcommittees. There was uncertainty about critical matters such as delegate numbers, costs and the total budget. Early decisions had to be made on, for example, the fee and fundraising target (£250,000), despite financial risks. Development of the scientific programme was a critical step that underpinned fundraising and marketing and permitted involvement of the international committee. Overall the 2011 WCE succeeded. The key ingredients to success were: a large collaboration of institutions and individuals; early pledges of financial support mostly from the UK; the valuable and relevant experience of the professional conference organisers; unstinting support and advice from IEA; and the effectiveness of the committee structure. The educational and professional development benefits of this WCE will reach a worldwide community and not just delegates, because of video, PowerPoint and textual accounts being open access on the Internet. This reach is unprecedented for IEA's World Congresses. We anticipate that the Congress will translate into better public health practice, better future Congresses, advances in epidemiology and improved population health.

Neural induction by the secreted polypeptide noggin.

The Spermann organizer induces neural tissue from dorsal ectoderm and dorsalizes lateral and ventral mesoderm in Xenopus. The secreted factor noggin, which is expressed in the organizer, can mimic the dorsalizing signal of the organizer. Data are presented showing that noggin directly induces neural tissue, that it induces neural tissue in the absence of dorsal mesoderm, and that it acts at the appropriate stage to be an endogenous neural inducing signal. Noggin induces cement glands and anterior brain markers, but not hindbrain or spinal cord markers. Thus, noggin has the expression pattern and activity expected of an endogenous neural inducer.

Long-term weight loss effects on all cause mortality in overweight/obese populations.

This systematic review assesses the long-term effectiveness of weight loss on all cause mortality in overweight/obese people. Medline, Embase and Cinahl were searched (1966-2005). Cohort studies and trials on participants with body mass index > or =25 kg m(-2), with weight change and mortality with > or =2-year follow-up, were included finally identifying 11 papers based on eight studies. There may be gender differences in the benefits for all cause mortality. The impact of weight loss in men on mortality was not clear with some studies indicating weight loss to be detrimental, while a recent cohort study showed benefits, if it were a personal decision. Other studies with no gender separation had similarly mixed results. However, one study indicated that overweight/obese women with obesity-related illness, who lost weight intentionally within 1 year, had significantly reduced mortality rates of 19-25%. In contrast, studies of overweight/obese diabetics irrespective of gender showed significant benefit of intentional weight loss on mortality in a meta-analysis, hazard ratios = 0.75 (0.67-0.83). There is some evidence that intentional weight loss has long-term benefits on all cause mortality for women and more so for diabetics. Long-term effects especially for men are not clear and need further investigation.

TGF beta inhibitors. New and unexpected requirements in vertebrate development.

Analysis of embryonic induction has pointed to the importance of the antagonistic roles played by secreted inducing factors and their soluble inhibitory binding proteins. These interactions have been particularly well characterized in patterning the primary axes of insects and vertebrates. New results implicate similar antagonistic relationships in numerous later events of embryogenesis.

Corticosteroids for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage which can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although the long-term effect is uncertain. OBJECTIVES: To assess the effects of corticosteroids on nerve damage in leprosy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register, the Cochrane Central Register of Controlled Trials (Issue 4), MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1980), LILACS (from 1982) in January 2006. We checked reference lists of the studies identified, the Current Controlled Trials Register (www.controlled-trials.com), conference proceedings and contacted trial authors. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of corticosteroids for nerve damage in leprosy. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in sensory and motor nerve function after one year. Secondary outcomes were improvement in nerve function after two years, change in nerve pain and tenderness, and adverse events. Two authors independently extracted data and assessed trial quality. We contacted trial authors for additional information. We collected adverse effects and cost effectiveness information from the trials and non-randomised studies. MAIN RESULTS: We included three randomised controlled trials involving 513 people. Two trials compared prednisolone with placebo. One trial treated mild sensory impairment of less than six months duration and the other trial treated nerve function impairment of 6 to 24 months duration. Both trials examined an effect twelve months from the start of treatment. There was no significant difference in nerve function improvement between people treated with prednisolone or with placebo. The third trial compared three corticosteroid regimens for severe type 1 reactions. This trial did not report the prespecified outcomes. However, after 12 months, a significantly higher proportion of individuals on a 3-month course of prednisolone required extra corticosteroids compared to the groups with a high-dose and low-dose regimen of five months duration. Diabetes and peptic or infected ulcer were sometimes reported as serious adverse events in the placebo-controlled trials, but not significantly more often in the corticosteroid than placebo groups. AUTHORS' CONCLUSIONS: Corticosteroids are used for treating acute nerve damage in leprosy, but evidence from randomised controlled trials does not show a significant long-term effect. Randomised controlled trials are needed to establish their effectiveness, the optimal regimens and to examine new therapies.

Promoting early detection in leprosy--a literature review to identify proven and potential interventions addressing patient-related delay.

OBJECTIVES: The objective of the literature review was to identify proven and potential interventions to promote early diagnosis and start of treatment in leprosy, specifically, forms of intervention addressing needs at the local or primary level. DESIGN: Using a structured search procedure, we identified recent leprosy-related publications describing proven interventions. To identify potential interventions the search was extended to publications assessing knowledge and attitudes towards leprosy and extended again to identify publications relating to patient-related delay in the context of other infectious diseases. RESULTS: The review identified just 19 publications reporting leprosy-related interventions that included a form of evaluation of which only 10 directly addressed patient-related delay. These included health education interventions focussed on people directly affected by leprosy, their family members and other key individuals or groups within the local community. We identified no reports of interventions focussed specifically on the needs of women. CONCLUSIONS: Our conclusion is that the evidence base available to inform the choice of small-scale interventions to promote early detection at the primary level is extremely limited. There is an urgent need to develop and extend the range of proven interventions, specifically those that address the needs of women, those that explore and develop the health promotion potential of people previously affected by,leprosy and those that exploit the potential of individuals with leadership roles within the community. This will require careful attention to planning, implementation, evaluation and reporting of interventions.

Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy.

OBJECTIVE: The objective of this randomized trial was to compare three different steroid regimens in treating type 1 reactions in leprosy in routine clinical practice. DESIGN: The study design was a multicentre, double-blind, randomized, controlled, parallel group trial in patients with acute reversal reactions. The trial was conducted in six leprosy treatment centres in India. A total of 334 participants with acute type 1 reaction were recruited to the trial and randomized to one of three prednisolone regimens: high dose (60 mg per day) or low dose (30 mg per day) both tapered over 20 weeks, and short duration (60 mg per day tapered over 12 weeks). The main outcome measure was the proportion of patients failing to respond to treatment and requiring additional steroids. RESULTS: At the end of 12 months, 46% on the short course required additional steroids compared with 31% on the low dose and 24% on the high dose regimen. CONCLUSIONS: The two 20-week regimens were significantly better than the 12-week regimen. The high dose 20-week regimen was marginally and non-significantly better than the low dose regimen, but the high dose regimen contained 50% more steroid. Reactions in leprosy persist over many months and require long courses of steroids.

The role of retinal photoisomerase in the visual cycle of the honeybee.

The compound eye of the honeybee has previously been shown to contain a soluble retinal photoisomerase which, in vitro, is able to catalyze stereospecifically the photoconversion of all-trans retinal to 11-cis retinal. In this study we combine in vivo and in vitro techniques to demonstrate how the retinal photoisomerase is involved in the visual cycle, creating 11-cis retinal for the generation of visual pigment. Honeybees have approximately 2.5 pmol/eye of retinal associated with visual pigments, but larger amounts (4-12 pmol/eye) of both retinal and retinol bound to soluble proteins. When bees are dark adapted for 24 h or longer, greater than 80% of the endogenous retinal, mostly in the all-trans configuration, is associated with the retinal photoisomerase. On exposure to blue light the retinal is isomerized to 11-cis, which makes it available to an alcohol dehydrogenase. Most of it is then reduced to 11-cis retinol. The retinol is not esterified and remains associated with a soluble protein, serving as a reservoir of 11-cis retinoid available for renewal of visual pigment. Alternatively, 11-cis retinal can be transferred directly to opsin to regenerate rhodopsin, as shown by synthesis of rhodopsin in bleached frog rod outer segments. This retinaldehyde cycle from the honeybee is the third to be described. It appears very similar to the system in another group of arthropods, flies, and differs from the isomerization processes in vertebrates and cephalopod mollusks.

Isolation of two molecular weight variants of the mouse growth hormone receptor.

GH receptors (GHRs) have been shown by affinity cross-linking to be present in late pregnant mouse liver microsomes in three forms with cross-linked mol wts of 125,000, 62,000, and 56,000. The two lower mol wt forms of the receptor were partially purified by bovine GH-affinity chromatography of 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate-solubilized extracts of late pregnant mouse hepatic microsomes. The GHRs were identified from the partially purified receptor preparation and isolated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isolated GHRs had mol wts of 40,700 and 37,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Enzymatic cleavage of N-linked glycosylation from the isolated GHRs reduced their apparent mol wts to 33,600 and 30,900, respectively. Sixteen of the amino-terminal 17 amino acid residues of the two isolated receptors were sequenced and determined to be identical. One amino acid residue in each of the proteins, at position 14, could not be identified. Rabbit polyclonal antiserum was produced against the isolated GHRs. The resulting antiserum precipitated the isolated 40,700 and 37,500 mol wt proteins as well as cross-linked mouse GHRs (including the high mol wt form of the receptor). However, the antiserum did not inhibit the binding of mouse GH to either membrane bound or 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate-solubilized GHRs.

Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains.

Predicted amino acid sequences for the mouse GH receptor and the related serum GH binding protein were deducted from cDNAs. Two types of cDNA clones were isolated. Both types coded an identical peptide domain with extensive homology to the extracellular domains of the recently cloned human and rabbit GH receptors. However, while one type of clone also encoded regions with homology to the transmembrane and cytoplasmic domains of the human and rabbit GH receptors, the other encoded a short hydrophilic carboxyl-terminal region in place of the transmembrane domain. It is speculated that these two types of clones encode the high and low molecular weight variants of the mouse GH receptor/serum binding proteins, respectively. The low molecular weight variant has been previously found to constitute the majority of the serum GH binding activity in mice. It is proposed that the substitution of the hydrophilic tail for the transmembrane domain may give the low molecular weight variant its soluble nature and account for its presence in serum.

Hamster placental lactogen-II contains a structural feature unique among the growth hormone-prolactin-placental lactogen family.

Sequence analysis of cDNA for hamster placental lactogen-II (PL-II) revealed that while this protein has a high degree of sequence homology to mouse and rat PL-II it contains a pair of cysteine residues not present in the mouse and rat proteins or in any other known member of the GH-PRL-PL protein family. This unique pair of cysteine residues may be responsible for the extreme tendency of hamster PL-II, compared to other members of the GH-PRL-PL family, to form disulfide-bonded hormone-serum protein complexes.

Factors contributing to delay in diagnosis and start of treatment of leprosy: analysis of help-seeking narratives in northern Bangladesh and in West Bengal, India.

The objective of our research was to identify factors contributing to delay in diagnosis and start of treatment in leprosy, focussing on patients' narratives of help-seeking behaviour. Our research took place in Purulia, West Bengal, India and in Nilphamari, northern Bangladesh. Between January and August 2000, we conducted semi-structured interviews with 104 patients that explored each individual's narrative of help-seeking behaviour and the context of beliefs and attitudes towards leprosy. Subsequently we surveyed 356 patients currently receiving treatment for leprosy and recorded specific aspects of each help-seeking action and their reports of local beliefs and attitudes towards leprosy. Delay was estimated from time of first symptoms through to start of effective treatment (mean 18 months, median 9 months in Purulia and mean 20 months, median 12 months in Nilphamari). The number of help-seeking actions ranged from 1 to 7. Time committed to first actions contributed 86% (Nilphamari) and 79% (Purulia) to total delay. The most important contributor to delay in the first action occurred when people simply monitored or ignored first symptoms, 80% in Nilphamari and 67% in Purulia. With delay longer than 12 months as outcome, logistic regression analyses identified age over 35 years, multiple visits to practitioners in traditional medicine and multiple visits to health service practitioners as predictive of delay. Attending a nearby clinic and exposure to health education materials were predictive of early presentation reduced delay.

Gestational profile and affinity cross-linking of the mouse serum growth hormone-binding protein.

The modulation of the serum concentration of mouse GH-binding protein during gestation was characterized. A rapid increase in the concentration of the binding protein began on day 9 of pregnancy and peaked by day 15. The increase in the serum GH-binding protein concentration was preceded several days by an increase in the hepatic GH receptor concentration. The serum GH-binding protein was recognized by antibodies produced against the hepatic GH receptor, and its mol wt (major form mol wt, approximately 41,800) was similar to that of low mol wt forms of the hepatic GH receptor, demonstrating the similarity of the serum GH-binding protein and the hepatic GH receptor. The apparent affinity of the serum GH-binding protein for mGH in untreated serum samples from 17-day pregnant mice was 6.9 X 10(7) M-1. However, when the serum was treated to remove endogenous GH, the apparent affinity increased to 1.5 X 10(8) M-1. Likewise, the binding capacity of the GH-binding protein in serum differed in treated (60.1 nM) and untreated serum (101.2 nM).

Hepatic placental lactogen receptors during pregnancy in the mouse.

The binding sites for mouse placental lactogen-II (mPL-II) in virgin and pregnant mouse hepatic membranes were analyzed by Scatchard analysis and affinity cross-linking. Competitive binding studies showed that mPL-II and mouse PRL (mPRL) bound to the same receptors in all liver membrane preparations, although the affinity of mPRL binding was lower than that of mPL-II binding. Two classes of receptors for mPL-II, high and low affinity, were found by Scatchard analysis. The concentration of both types of sites in liver membranes increased during pregnancy. In contrast, the affinity of both sites for mPL-II was highest in virgin female mice and declined during pregnancy. Cross-linking of [125I]iodo-mPL-II to maternal liver membranes resulted in the specific labeling of one major protein species of 67,000 daltons as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Under nonreducing conditions, two bands of approximately 63,000 and 60,000 daltons were apparent. Subtraction of the mol wt of mPL-II (22,000, reduced; 20,000, nonreduced) from the mol wt of the cross-linked complex indicated that the mol wt of the receptor was 45,000 under reducing conditions and 43,000 and 40,000 under nonreducing conditions. These observations suggest that mPL-II receptors may be present in mouse liver membranes in at least two forms.

Recombinant mouse placental lactogen-I binds to lactogen receptors in mouse liver and ovary: partial characterization of the ovarian receptor.

The binding of recombinant mouse placental lactogen-I (mPL-Ir) to liver and ovarian membranes was investigated in virgin and pregnant mice. Competitive binding assays demonstrated that mPL-Ir, mouse placental lactogen-II (mPL-II), and mouse PRL (mPRL) bind to the same receptors in ovarian membranes. The relative abilities of the three hormones to displace [125I]iodo-mPL-Ir from the ovarian lactogen receptors was mPL-II greater than mPL-Ir much greater than mPRL. Scatchard analysis of mPL-Ir binding to ovarian membranes from day 10 pregnant mice showed a Ka of 2.0 x 10(9) M-1 and a binding capacity of 3.2 x 10(-14) mol/mg membrane protein. The specific binding of [125I]iodo-mPL-Ir to ovarian membrane preparations was significantly higher on day 17 than on day 10 of gestation. Dissociation of endogenous hormones with 4 M MgCl2 increased the binding of [125I]iodo-mPL-Ir to ovarian membranes but not to liver membranes. Affinity cross-linking of [125I]iodo-mPL-Ir to liver and ovarian membranes resulted in the specific labeling of proteins with receptor mol wt (Mr) of 44K and 40K (nonreduced) and 50K and 42K (reduced), as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lactogen receptors from liver and ovary appeared structurally homologous, producing fragments with similar Mr when treated with proteolytic enzymes and undergoing similar reductions in Mr when treated with glycolytic enzymes. The ability of mPLs to bind specifically and with high affinity to receptors in mouse ovarian membranes suggests that these hormones may regulate ovarian function during gestation.

Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse.

[125I]Iodomouse GH [( 125I]iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse.