Engaging multisector stakeholders to identify priorities for global health innovation, change and research: an engagement methodology and application to prosthetics service delivery in Cambodia.

PURPOSE: While innovation is known to catalyse solutions to global sustainable development challenges, lack of engagement from stakeholders during conceptualisation and development may influence the degree of success of implementation. METHODS AND MATERIALS: This paper presents a complete and novel engagement methodology, developed from value led business modelling approaches, for working with multi-sector stakeholders. The methodology can be used to determine barriers and facilitators to clinical practice innovations or translational research, within a country-specific context. The approach has then been applied in the Cambodian prosthetics and orthotics sector to provide a practice-based exemplar application of the framework. RESULTS: This approach seeks to ensure the suitability and sustainability of clinical practice and research programmes being implemented within a complex ecosystem. A theoretical basis, drawn from academic and business innovation sectors, has been consolidated and adapted for practical application to design, direct, and inform initiatives in low resource settings. CONCLUSIONS: The methods presented provide a way to both develop and articulate the mission, vision, and goals of any proposed change, and to effectively communicate these with stakeholders in a way that engages the personal and professional values that exist in their ecosystem. It provides a structured process through which meaningful conversations can happen, and a basis for relationship management with key stakeholders; intrinsic to enable a sustained legacy from research and development.

The engagement from stakeholders during conceptualisation and throughout development can determine the success, or not, of any implementation and scale of innovation.This paper presents a conceptual stakeholder-led engagement methodology, developed from value led business modelling approaches, for determining barriers and facilitators to translational global healthcare research in a country-specific context, in this case the Cambodian prosthetics and orthotics sector.Subsequent research and development work in this area needs to carefully manage and negotiate influencing factors identified through the application of the described methodology, to ensure initiatives (whether research or wider national development work) are sustainable and successful.

Association between cigarette smoking and erectile tumescence: the mediating role of heart rate variability.

Cigarette smoking deleteriously affects erectile function, and conversely, quitting smoking improves erectile hemodynamics. Underlying mechanisms by which smoking (or reduction of smoking frequency) may affect erectile physiology are not well understood. This study examined the mediating role of heart rate variability (HRV; a marker of sympathovagal balance) among a sample of male chronic smokers from the United States. Sixty-two healthy men (Mage=38.27 years; s.d.=10.62) were assessed at baseline (while smoking regularly), at mid-treatment (while using a nicotine patch) and at follow-up, 4 weeks after patch discontinuation. Cigarette use, frequency-domain parameters of HRV (low frequency (LF), high frequency (HF), LF/HF ratio) and physiological sexual arousal responses (via penile plethysmography) were assessed at each visit. Results were consistent with mediation, in that greater reductions in cigarette use from baseline to follow-up were associated with longitudinal increases in LF, which in turn showed positive relationships with across-time changes in erectile tumescence. Neither HF nor LF/HF ratio mediated the relationship between smoking and erection. In conclusion, HRV mediated the inverse relationship between reductions in smoking and enhancements in erectile tumescence. Results underscore the possibility that cigarette use may deleteriously affect erectile function peripherally, in part, by disrupting cardiac autonomic function.

The effects of nicotine and sucrose on spatial memory and attention.

Both nicotine and sucrose can enhance performance on cognitive tasks. However, little is known about whether nicotine and sucrose could act jointly to augment mental performance. To investigate if there is an interaction between nicotine and sucrose on cognitive behavior, performance on a continuous performance task (CPT) and a spatial memory task was examined in 14 healthy smokers after they had drunk 8 oz of either a sucrose- or aspartame-containing beverage, and then chewed a piece of gum containing either 2 mg nicotine or no nicotine. To assess changes in mood as a function of nicotine and sucrose intake, the profile of mood states (POMS) test was administered three times during each test session. Participants made significantly more correct responses and significantly fewer incorrect responses on the CPT when they received nicotine than when they received the placebo gum. Closer analysis of the data revealed that there was an interaction between sucrose consumption and nicotine intake. Nicotine increased hits and decreased misses when participants were given the sucrose-containing beverage, but not when they were given the aspartame-containing beverage. Neither nicotine nor sucrose affected spatial memory or mood across experimental sessions. However, when data were analyzed for just the first session, participants who drank the sucrose-containing beverage performed significantly better on the spatial memory task than those who drank the aspartame-containing beverage. No gender differences in the effects of nicotine or sucrose on cognitive performance were detected. The results provide support that both nicotine and sucrose have positive effects on cognitive behavior, and that under some conditions the two variables have additive effects on performance.

Efficacy of nonprescription doses of ibuprofen for treating migraine headache. a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of ibuprofen, 200 mg and 400 mg, compared with placebo and each other for the treatment of pain of migraine headache. BACKGROUND: Migraine headache is a common illness with significant social and economic impact. DESIGN: Randomized, placebo-controlled, double-blind trial of 6 hours' treatment duration. METHODS: Fifteen investigators at 17 private practice and referral centers in the United States participated in this study of 660 outpatient adults aged 18 to 84 years with migraine headache of moderate to severe intensity. Each patient was randomly assigned to a single dose of study medication: ibuprofen 200 mg (n = 216) or 400 mg (n = 223), or placebo (n = 221). The percentage of patients with a reduction in baseline headache intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Secondary outcomes included other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none. RESULTS: Significantly (P < or = .006) more patients treated with ibuprofen, 200 mg or 400 mg, reported mild to no pain after 2 hours (41.7% and 40.8%, respectively), compared with those treated with placebo (28.1%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < or = .001) greater for patients treated with ibuprofen 200 mg or 400 mg (0.68 and 0.65, respectively), compared with those treated with placebo (0.39). Statistically significant differences in favor of both doses of ibuprofen over placebo were observed for mean pain intensity difference at 1 hour after treatment. In patients with severe baseline pain intensity, ibuprofen, 400 mg, was significantly (P < or = .048) superior to placebo for the primary efficacy end points, while ibuprofen, 200 mg, was not. Ibuprofen, 200 mg and 400 mg, were statistically significantly more effective than placebo for all clinically important secondary pain relief outcomes. Mean severity changes of migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < or = .03) in favor of both doses of ibuprofen over placebo, and results for the percentage of patients with symptoms reduced to none consistently, although less often statistically significant, favored ibuprofen. No statistically significant differences in adverse events were found among treatment groups. CONCLUSIONS: Ibuprofen at doses of 200 mg and 400 mg is an efficacious, cost-effective, well-tolerated, single-ingredient nonprescription treatment for pain of migraine headache. In addition, while not always statistically significant, ibuprofen provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.

Progestogens and Cushing's syndrome.

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing's syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg/day but Cushing's syndrome has been reported in patients taking 400 mg/day. Neither the glucocorticoid-like effects or Cushing's syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing's syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing's syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.

Effects of precoating surface treatments on fatigue of Ti-6A1-4V.

Grit blasting is a common procedure of roughening surfaces to promote physical attachment of porous coatings, but it has been shown to reduce fatigue strength. Shot peening is known to increase fatigue strength by inducing compressive surface stresses; however, it is not known how subsequent grit blasting affects these benefits. This study examines the endurance limits, Se, of ELI grade Ti-6A1-4V specimens under rotating cyclic bending, including polished (control); belted and beaded; belted, beaded, and grit blasted; and belted, beaded, shot peened, and grit blasted. Belting and beading resulted in a slight increase in Se, grit blasting caused a 15% reduction in Se from polished. Fifty percent of this reduction was recovered when shot peening preceded grit blasting, suggesting that residual compressive surface stresses, induced by peening, were not eliminated by the blast process. Roughness averages and RMS values did not correlate with Se trends. SEM results showed classical fatigue fractures, consistent with surface crack initiation.

Gene-dependent male sterility and plastomes in Oenothera.

The plastids in the cells of the tapetum in anther of Oenothera are involved in the development of male sterility (mst). We combined nuclear homozygosity for each of the two mst genes with the four different plastomes of Oenothera and demonstrated that in both cases the sterile anther phenotype is independent of the plastome. The experiments provide additional information on competition between megaspores and embryo sacs in the ovule.

[Mutations in Oenothera hookeri after prolonged influence of radiowaves during one vegetationperiod]. / Mutationen bei Oenothera hookeri nach Dauereinwirkung von Meterwellen während einer Vegetationsperiode.

Plants of Oe. hookeri were grown under the influence of a radiostation during one vegetationperiod (M 0-generation). After selfing and crossing of pollen of these plants on emasculated, untreated flowers, in the M 1- and M 2-generation an increase of lethal embryos, plants with reduced viability and morphological variability of quantitative characters was observed. In M 2 6 families out of 23 gave rise to a monogenic mutant, 2 families segregated for 2 mutants each. The mutations occurred as somatic mutations in the M 0-plants, as meiotic or gametophytic mutations or as somatic mutations in the M 1-embryos. These results are an additional proof for the mutagenic action of radio-waves.

[Genetic mosaics in the second generation of Oenothera hookeri after treatment with radiowaves]. / Genetische Mosaike in der M 2 bei Oenothera hookeri nach Behandlung mit Meterwellen.

Morphological mosaic plants were observed in the second generation after a mutagenic treatment of pollen and plants of Oenothera hookeri. The abnormal parts showed differences in colour or form of the leaves. The progeny of the normal parts were normal, the abnormal sectors gave rise to several mutants. This proved the plants to be genetic mosaics. The mutants are described. The mosaics lead to conclusions about the growth in the apex and the leaf primordium. The delay in the occurrence of the mutations is interpreted as a genetic lability after the mutagenic treatment.

[Competition between pollen tubes of Oenothera, dependent on the maturation of the style]. / Abhängigkeit der Gonenkonkurrenz im Pollen vom Entwicklungszustand des Griffels bei Oenothera.

In backcrosses of hybrids, which show a competition of genotypes in the pollen, the segregation depends on the developmental condition of the style at the time of pollination.The pollination of young styles with pollen of the hybrids gives a more normal segregation. The results are compatible with the hypothesis, that the relative inhibition under the influence of the allel ga (-) acts at the germination of the pollen grains and the first stages of development of the pollen tubes in the style.

[Mutations in Oenothera hookeri after treatment of the pollen with radio waves]. / Auftreten von Mutationen bei Oenothera hookeri nach Behandlung des Pollens mit Meterwellen.

Pollen of Oenothera hookeri was exposed to radio waves (λ = 1,5 m; 1,4 and 1,8 mV/m) for 4 and 12 hrs. This pollen was crossed to normal emasculated flowers. The M 1-generation and the M 2- and M 3-generations were investigated. The criteria for a mutagenic action of the treatment were: haploid plants in M 1; partial pollen lethality in M 1, some due to chromosomal abnormalities; genetic heterogeneity of M 1 plants for lethal genes and for genes for reduced vitality as determined by the frequency of seeds with lethal embryos in M 2; segregation of morphological abnormalities in M 2. All experiments demonstrated the mutagenic effect of the radio wave treatment.

[Competition between the male gametophytes in Oenothera under the influence of a gametophytic gene in the first linkage group and a model for investigations of branched genetic maps]. / Gonenkonkurrenz bei Oenothera unter dem Einflu\ eines gametophytisch wirksamen Gens in der ersten Koppelungsgruppe sowie ein Modell für die Untersuchung verzweigter Koppelungsgruppen.

The progeny ratios obtained in male backcrosses of Oenothera hybrids to the complexes hookeri and flavens (identified by two marker genes and by the translocation break) showed statistically significant differences from Mendelian expectations.Presence of a gametophytic gene in the first linkage group is proposed. Its alleles ga (+) and ga (-) are thought to control development of the male gametophytes in such a manner that pollen grains carrying the different ga alleles and developing in a heterozygous female plant, will fertilize the female gamete with different average frequencies.A series of genetic models is developed, all taking into account the relative probability of the alleles ga (+) and ga (-) to function in fertilization, the probability of crossing over between the gene loci studied, and the branched configuration of the linkage group, due to the presence of the translocation.Based on these models, the relationships between the relative frequencies of the different classes of gametes are predicted for several theoretically possible arrangements of the genes within the linkage group.The models have general application for the localization of gametophytic genes and for the localization of genes in branched linkage groups.It turns out to be impossible to give an estimate for the disadvantage of ga (-) as compared to ga (+) from the backcross data alone. The empirical data permit only a combined estimate of the probabilities of fertilization by ga (-) and of crossing over between Ga and the locus of the marker gene.Comparison between the empirical data and the model makes it possible to determine the location of the marker loci and the locus of Ga with respect to one another. A branched linkage group appears most likely, but a linear arrangement in two chromosome arms cannot be ruled out.The observed cross-over values, and consequently, the map distances between the genes studied, are highly variable, both in different hybrids and in the progeny of a single hybrid.

[Competition between haploid cells in the ovary of Oenothera]. / Gonenkonkurrenz in der Samenanlage von Oenothera.

Investigations were made on the segregation of the genes s, de and of the translocation point of the first linkage-group in the progeny of backcrosses of heterozygotes of Oenothera with the complexes (h) hookeri and flavens with Oe. hookeri sulfurea ♂. The deviations from mendelian expectation are statistically significant. The phenotype corresponding to the hookeri-parent of the F1 occurs with the greatest relative frequency.An interpretation of the results is given on the assumption that in the first linkage group, which appears cytologically as a translocation group of four chromosomes, a gene with gametophytic action is located. The complex (h) hookeri contains the allel ga-♀(+), the complex flavens ga-♀(-). These alleles influence the development of the haploid cells in the ovary in such a way that in a heterozygote mother plant the haploid cells with the allel ga-♀(+) have a greater chance to form the embryosac and the egg cell than haploid cells with the allel ga-♀(-).There is a strong negative interference in the parts of the chromosomes adjacent to the translocation point.The variability of the recombination of the three loci leads to the assumption of highly variable crossover-values in the chromosomes here investigated. A correlation between this variability of crossing-over and of the negative interference with pairing anomalies in a translocation group is taken into consideration.Hypotheses concerning the genetic basis of the competition between haploid cells in the ovary and the anther and the action of these gametophytic genes are discussed.

[Certation experiment concerning competition between pollentubes under the influence of the locus Ga in Oenothera]. / Certationsversuch zur Gonenkonkurrenz unter dem Einfluß des Locus Ga bei Oenothera.

The material for the experiments were two Oenothera-Hybrids with the complexes (h) hookeri and flavens which were heterozygous for the gametophytic gene ga and for the genes s and de. Certation experiments were done by pollinating the styles of Oe. hookeri sulfurea with different amounts of pollen grains and by interruption of pollen tube growth by cutting off the styles at different times after pollination.There is no correlation between the experimental treatment and the segregation for the two genes in the progeny. The competition between pollen cells with the alleles respectively ga (+) and ga (-) therefore cannot be due to differences in growth rates during the developmental stage of pollen tube-growth in the style but must occur during the germination of the pollen on the stigma or in the last stage of development of the pollen tubes shortly before fertilization. The data reveal great variability of crossing-over in the chromosome-region under investigation.

[Competition in Antirrhinum majus L]. / Gonenkonkurrenz bei Antirrhinum majus L.

In Antirrhinum majus selection in the haplophase is investigated, using the segregation in the backcrossprogeny of heterozygotes cae/+(cae)(color of petal-spot).An attempt was made to determine whether the competition depends on gene-action of the locus caeca itself or on a gametophytic gene located in the same chromosome. Three types of progenies can be distinguished: Normal mendelian segregation, or statistically significant deviations with a surplus of "yellow spot" or a surplus of "light, nearly colorless spot" respectively. The hypothesis of an action of the locus cae in the haplophase can be rejected on the basis of these data.The location of a gametophytic gene in the gram-chromosome is assumed. The allele ga (+) comes from the line fim del cae, the allele ga (-)from the standard line S 50. Gametes with the allele ga (+)have a greater chance for fertilization than gametes with ga (-). The competition is found in the progeny of pollen and of egg cells. Two explanations are possible: one gene, which acts in the haplophase irrespective of the sex, or two closely coupled loci, which act in a similar way in the haplophase of each sex respectively. The locus ga is located either between cae and del or distal from cae.