From Surviving to Thriving: Evaluation of the International Diabetes Federation Life for a Child Program

IDF-LFAC aims to provide: (1) insulin and syringes; (2) blood glucose monitoring (BGM) equipment; (3) appropriate clinical care; (4) HbA1c testing; (5) diabetes education; and (6) technical support and training for health professionals, as well as 7) facilitating relevant clinical research, and where possible 8) assisting with capacity building. IDF-LFAC receives financial and in-kind support from private foundations, individuals, and corporations. Insulin and blood glucose monitoring equipment distribution is made possible by donations of insulin and the purchase of blood glucose monitors and strips at a reduced price from large pharmaceutical companies.The goal of this evaluation is to assess IDF-LFAC's organizational structure, strategic framework, processes, program impact, and potential to catalyze longterm sustainable improvements to T1D care delivery systems in its partner countries. LSHTM were commissioned to undertake the evaluation in 2014 when IDF-LFAC had active programs in 45 countries

Puerperal infection: with special reference to the value of blood cultures in the various stages of this condition, and to the question of 'autoinfection'

Since the introduction of aseptic and antiseptic methods into Midwifery the incidence of Puerperal Fever has diminished enormously. But when we compare the results obtained in Midwifery, with those obtained in Surgery it must be admitted that the improvement is not proportionate. Still sepsis does occur in cases where every precaution has been taken. We have however inherited the view that sepsis is preventible in every case, that carelessness on the part of the accoucheur is responsible for its occurrence, and that, should a case become infected the essential part of the treatment is to take steps to ensure the complete emptying of the Uterus.Therefore, when new ideas are brought forward and the suggestion made that patients may carry in the Vagina organisms which may give rise spontaneously to sepsis in the Puerperium and that mole harm than good may be done by removing fragments of placenta from an already infected Uterus, it is a long time before these suggestions are seriously considered.Work has been done in the endeavour to solve the first- mentioned problem, since the end of last century, chiefly in Germany and in America. The second debatable point - that the hitherto recognised treatment of infected cases by douching, and removing remnants of placenta etc. has no sound foundation in Pathology - was brought forward in Germany in 1910. American observers then became interested and began to investigate the matter. This country, always a conservative one, has only recently begun to consider the question. At a meeting of the Obstetrical Society in Edinburgh in 1923, Professor Watson brought forward this view and raised a lively discussion.Certainly both questions, if they offer any explanation of the obstinately high mortality statistics, are well worth studying. In Scotland more than six pregnant patients in every 1000 die from diseases or accidents of childbirth and 25 -50% of these deaths are due to Puerperal Fever; i.e. about 2000 patients die annually in the United Kingdom from this disease, and there is no indication that this high mortality is decreasing.The evidence which r have endeavoured above to collect, seems to point to the following facts : -1. The Vagina frequently contains organisms, even haemolytic Streptococci, in apparently uninfected non -pregnant and pregnant patients. There is no evidence to prove that these are other than harmless saprophytes.2. It is only in exceptional cases that these organisms are likely to cause Puerperal Fever.3. Infection in the puerperium is therefore probably due to a recently introduced virulent organism or to one which has ascended from the Vulva after delivery.4. The Vagina and Uterus always contain organisms, frequently Streptococci, in cases of incomplete abortion. These organisms can cause putrefaction in the Uterine contents without a rise of temperature if drainage is sufficient.5. During contractions any or all of the organisms in the Uterus can and do reach the circulation. They cause rigors, but are soon destroyed by the blood. This type of bacteraemia is not a serious one.6. Even when Streptococci appear in the blood under these circumstances, they are probably of the same variety as the harmless saprophytic Streptococci found in the aborting uterus.7. Mechanical intrauterine manipulations in these cases likewise cause a flooding of the blood stream with organisms.8. In a certain proportion of febrile abortion cases, actual infection with virulent organisms is present, and operative interference in these cases causes dissemination of the organisms into the blood stream, and inoculation more deeply into the tissues.9. In the puerperium itself organisms do not invade the blood stream from the interior of the uterus in the same massive way unless there is interference.10. When organisms do appear spontaneously they are in the vast majority of cases pathogenic and are derived from a septic phlebitis, or an endocarditis, or a general septicaemia is present.11. In the puerperium as in incomplete abortion, interference can cause invasion of the blood- stream from the interior of the Uterus and can convert a surface inflammation into a general blood infection.12. The retention of a piece of placenta is not the factor which determines whether a patient is going to develop a severe infection or not.13. No attempt should be made to remove such a piece of placenta while the patient is febrile, because of the above danger.14. Severe bleeding which is likely to endanger life is the only indication for intrauterine manipulation in these cases

Performance characterisation of photovoltaic devices: managing the effects of high capacitance and metastability

It is essential to make performance measurements of photovoltaics modules in order to quantify the power they will produce under operational conditions. Performance measurements are fundamental throughout the photovoltaic industry, from product development to quality control in manufacturing and installation in the field. Rapid and economic evaluation of photovoltaic performance requires measurements using pulsed illumination solar simulators. However some devices have characteristics which can cause difficulties making these measurements. The aim of this thesis is to overcome these measurement problems focusing particularly on two of the most prevalent and pressing of these problematic characteristics: high capacitance and metastability. A new method for measuring high capacitance modules in a pulsed simulator, based on tailor made voltage ramps, was developed. The voltage ramp is tailor made such that the measurement time is minimised while maintaining high accuracy (0.5 %), allowing the measurement of high capacitance modules in a single 10ms illumination pulse. The necessary inputs for this method are the capacitance and dark current as a function of voltage for each module. In order to make these measurements, at the high forward bias voltages required, a new system was developed. The tailored voltage ramp can be created individually for each module, since the process is rapid an automatic. This makes the method applicable to a production line or to test house measurements. In addition to their use as inputs for the voltage ramp design, the capacitance and dark current also contain other valuable information, including effective minority carrier lifetime. In several thin film technologies, such as CIGS, the efficiency is not a fixed value, rather the module is metastable and the efficiency changes depending on the previous exposure /preconditioning of the device. Preconditioning is normally applied to these devices before measurement in order to put them in a specific state that is repeatable and representative of outdoor operation. Improved preconditioning practices are vital for performance measurements in CIGS modules. Therefore the preconditioning behaviour of a variety of CIGS modules from different manufacturers was investigated. The effect of preconditioning varied for different modules, commonly the fill factor improved substantially, but often changes in open circuit voltage were also seen and in some cases also substantial changes in short circuit current. The rates of preconditioning and relaxation were found to follow stretched exponential behaviour, such that the changes occur linearly on a logarithmic timescale over several orders of magnitude in time. The total time for performance stabilisation was found to vary significantly between different types of module. Because of this stretched exponential behaviour, even though the module took days to fully relax to the dark state, there was significant relaxation within the tens of minutes that it would normally take a module to cool down after light soaking before it could be measured. The major implication of observed kinetics is that in order to achieve repeatable measurement the timing in each element of a preconditioning routine should be controlled such that the fractional error in the duration of each step is small. During the investigation an unexpectedly short timescale preconditioning effect was observed, which occurs on a millisecond timescale and relaxes in seconds. It was shown that the measurement artefacts introduced using this method can be eliminated by using electrical forward bias until immediately before the measurement. Another measurement system was developed to track the dark current and C-V characteristic of the modules during electrical bias preconditioning and subsequent relaxation. These measurements demonstrate that more than one process involved during preconditioning in CIGS. Changes occur both in the doping in the bulk of the absorber and also in charge accumulation occurring near to the absorber / buffer interface. The theoretical models for preconditioning in CIGS were reviewed and compared to the experimental results. A rate model was developed based on the theory of the metastable VSe-VCu defect. This model was shown to correspond well to the rates of preconditioning and relaxation in CIGS. The non-exponential behaviour was shown to be compatible with a distribution of activation energies for the transition between different defect states. The difference in the time taken for modules to stabilise is explained by differences in doping density and the density of VSe-VCu defects. The work presented facilitates more accurate, economical performance measurements for high capacitance devices and CIGS devices, thereby contributing to the large scale implementation of photovoltaics as power source

Parameter Optimization of Conceptual Hydrological Models

The form of modelling used in this research for the simulation of the rainfall/runoff regime of catchment areas by mathematical models is of particular importance to civil engineers in the building of dams, river bridges and other works affected by high and low flows in rivers and streams. The parametric conceptual models can also be used in the management of water resources and as a basis for the assessment of long term risks associated with water storage and transmission of supplies. The objectives of this research are to examine the problems arising from the conceptual modelling of catchment areas with large data sets, and the effective determination of model parameters using gradient and non-gradient optimization techniques in the field of hydrology. A simple model package was developed from the application and modification of ideas current at the time which allowed a good fit to observed hydrographs to be achieved with the input of rainfall data and data for an evaporation loss function. Nine parameters were available for optimization in this model. The practical demand for the assessment of land use and its variations on catchment water yield led to the development of a more complex model with thirty five parameters based on the latest vegetation process studies. One of the first modifications was to the criterion for convergence where it was changed from the rate of change of parameter values to that of the model coefficient of determination or efficiency of fit. The least squares objective function was investigated, and retained for model explained variance. However, for parameters involved in the simulation of base flows it was found to be more effective to use a proportional function, whilst for intense storm events an eighth power function exaggerated the information available in the data for determination of surface runoff parameters. The models employ an input data 'overlay' technique which allowed the use of large data sets running over many years. The simulation results from land use changes with large data sets from the highlands of Scotland, a clay catchment in Buckinghamshire and montane rain forest in Kenya are compared and contrasted for both models. The results for these catchments using gradient and non-gradient optimization algorithms are also examined, including the use of a genetic algorithm, and recommendations made for the values of algorithm parameters. Hybridized algorithms are developed and tested. A combination of the Rosenbrock and Nelder and Mead Simplex techniques was found to be an efficient hybrid; particularly with the land use model

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials

Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.

Background The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening.Methods and findings A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose.Conclusions Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness

Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.

BACKGROUND: The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening. METHODS AND FINDINGS: A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose. CONCLUSIONS: Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness