Obesity disease management opportunities and barriers

Disease management, a system of coordinated health care interventions and communications for chronically ill populations, relies on patient education and case management to engage individuals in the management of their condition. Disease management also aims to enhance the quality of interactions between doctors and patients and advance evidence-based medicine. Because these programs' interventions frequently include helping individuals who suffer comorbidities associated with obesity to reduce their BMI, adaptation of disease management to populations with obesity seems a viable option. A major barrier for implementing disease management for obesity, however, is the lack of proven return on investment, which limits health plan and disease management organization interest. Purchaser demand may overcome this reluctance. Further research is needed to objectively test whether disease management interventions would be clinically effective for obese populations, produce positive financial outcomes for insurers, and enhance workplace productivity.     

Ecosystem health through ecological restoration: barriers and opportunities

It is quite possible that no ecosystem on the planet is totally free of anthropogenic effects. Changes in the ozone layer, airborne transport of contaminants, and the persistence of pesticides and other chemicals, coupled with biological magnification, implies that even remote areas are probably not comparable to their condition before the industrial revolution and the recent explosion of human population. Theoretical ecologists have attempted to isolate their theories and studies from anthropogenic effects with varying degrees of success. However, finding ecosystems free of the effects of human society is becoming increasingly difficult, partly because of the global nature of pollution problems. Regrettably, many academicians are not educated in policy development as they work toward B.S., M.S., or Ph.D. degrees in the sciences. As a consequence, scientists are surprised to learn that a politically-appointed individual, experienced in law or some other non-scientific field, usually has final decision-making authority over policy that affects ecosystems. Scientists must understand that policy links science to social, economic, and legal societal values and needs. Finally, aside from the fact that policy or lack thereof now affects all of the planet's ecosystems, policy most likely will also determine which areas of research are funded. While some scientific studies could be carried out with personal funds, these are not particularly common in mainstream science and, therefore, obtaining financial support for ecosystem studies for the remainder of this century and probably early in the next will depend increasingly on societal policy other than purely science policy.     

Adaptive enrichment designs with a continuous biomarker

A popular design for clinical trials assessing targeted therapies is the two-stage adaptive enrichment design with recruitment in stage 2 limited to a biomarker-defined subgroup chosen based on data from stage 1. The data-dependent selection leads to statistical challenges if data from both stages are used to draw inference on treatment effects in the selected subgroup. If subgroups considered are nested, as when defined by a continuous biomarker, treatment effect estimates in different subgroups follow the same distribution as estimates in a group-sequential trial. This result is used to obtain tests controlling the familywise type I error rate (FWER) for six simple subgroup selection rules, one of which also controls the FWER for any selection rule. Two approaches are proposed: one based on multivariate normal distributions suitable if the number of possible subgroups, k, is small, and one based on Brownian motion approximations suitable for large k. The methods, applicable in the wide range of settings with asymptotically normal test statistics, are illustrated using survival data from a breast cancer trial.     

Harnessing the developmental potential of nucellar cells: barriers and opportunities

Angiosperm nucellar cells can either use or avoid meiosis in vivo, depending on the developmental context. This unique ability contrasts with the conditions required in vitro, either for a reconstituted oocyte to avoid meiosis and produce clones by somatic cell nuclear transfer (SCNT), or for mammalian stem cells to undergo meiosis and produce synthetic sex cells (gametes). Current biotechnological initiatives to harness the potential of nucellar cells are based on the transfer of apomixis genes to sexual crop plants with the aim of producing clones through seeds. The elusive genetic basis of apomixis compels us to examine whether this process involves epigenetic factors. The elegant and versatile developmental platform available in nucellar cells should be explored as a genome-scale science and compared with mammalian stem cell biology for a holistic understanding of developmental programming and reprogramming in eukaryotes.     

Microalgal reactors: a review of enclosed system designs and performances

One major challenge to industrial microalgal culturing is to devise and develop technical apparata, cultivation procedures and algal strains susceptible of undergoing substantial increases in efficiency of use of solar energy and carbon dioxide. Despite several research efforts developed to date, there is no such thing as "the best reactor system"- defined, in an absolute fashion, as the one able to achieve maximum productivity with minimum operation costs, irrespective of the biological and chemical system at stake. In fact, choice of the most suitable system is situation-dependent, as both the species of alga available and the final purpose intended will play a role. The need of accurate control impairs use of open-system configurations, so current investigation has focused mostly on closed systems. In this review, several types of closed bioreactors described in the technical literature as able to support production of microalgae are comprehensively presented and duly discussed, using transport phenomenon and process engineering methodological approaches. The text is subdivided into subsections on: reactor design, which includes tubular reactors, flat plate reactors and fermenter-type reactors; and processing parameters, which include gaseous transfer, medium mixing and light requirements.     

Ammonia-Oxidizing Bacteria (AOB): opportunities and applications—a review

Recently, partial nitrification has been adopted widely as a first step of both nitrite shunt and deammonification processes towards efficient and economical nitrogen removal from wastewater. Effective partial nitrification relies on stimulating the first step of nitrification while inhibiting the second step and by consequence accumulating ammonia-oxidizing bacteria (AOB). Successful AOB accumulation depends upon the knowledge of their microbial characteristics and kinetics parameters as well as the main parameters that can selectively inhibits NOBs’ growth or allow AOBs to outcompete them. Several bioreactors configurations either in suspended or attached growth have been used towards achieving partial nitrification using different inhibition conditions. This review aims to illustrate an up to date version of the metabolism and factors affecting AOB growth and summarize the current bioreactors configurations in all lab-scale and full-scale applications for AOB. Moreover, successful partial nitrification attempts in the literature in suspended and attached growth systems have been complied. Additionally, the possibility of improving the current applications of AOB and the integration into the operation of existing WWTPs in order to transform into water resources recovery facility has been presented.     

Sample size recalculation in internal pilot study designs: a review

The adequacy of sample size is important to clinical trials. In the planning phase of a trial, however, the investigators are often quite uncertain about the sizes of parameters which are needed for sample size calculations. A solution to this problem is mid-course recalculation of the sample size during the ongoing trial. In internal pilot study designs, nuisance parameters are estimated on the basis of interim data and the sample size is adjusted accordingly. This review attempts to give an overview on the available methods. It is written not only for biometricians who are already familar with the the topic and wish to update their knowledge but also for users new to the subject.     

Mining the isotopic complexity of nitrous oxide: a review of challenges and opportunities

Nitrous oxide (N₂O) is an important focus of international greenhouse gas accounting agreements and mitigation of emissions will likely depend on understanding the mechanisms of its formation and reduction. Consequently, applications of stable isotope techniques to understand N₂O cycling are proliferating and recent advances in technology are enabling (1) increases in the frequency of isotope analyses and (2) analyses not previously possible. The two isotopes of N and 3 isotopes of O combine to form a total of 12 possible isotopic molecules of N₂O. Consequently, this remarkably simple molecule contains a wealth of isotopic information in the form of bulk (δ¹⁵N, δ¹⁸O), position dependent (site preference), mass independent (Δ¹⁷O) and multiply-substituted or clumped isotope compositions. With recent developments in high-mass resolution double sector instruments all 12 isotopic molecules will likely be resolved in the near future. Advances in spectroscopic instruments hold the promise of substantial increases in sample throughput; however, spectroscopic analyses require corrections due to interferences from other gases and frequent and accurate calibration. Mass spectrometric approaches require mass overlap corrections that are not uniform between research groups and interlaboratory comparisons remain imprecise. The continued lack of attention to calibration by both funding agencies and investigators can only perpetuate disagreement between laboratories in reported isotope values for N₂O that, in turn, will compromise global assessments of N₂O sources and sinks based on isotope ratios. This review discusses the challenges and opportunities offered by the isotopic complexity of N₂O.     

Convention on Biological Diversity: a review of national challenges and opportunities for implementation

The Convention on Biological Diversity (CBD) lies at the heart of biodiversity conservation initiatives. It offers opportunities to address global issues at the national level through locally grown solutions and measures. This article reviews the national challenges and opportunities in meeting requirements of the CBD by analysing twenty Third National Reports (TNRs), covering five different CBD regional clusters from the three global economic groups. While there is a plethora of challenges, the predominant ones discussed in this study include: institutional and capacity, knowledge and accessible information, economic policy and financial resources, cooperation and stakeholder involvement, and mainstreaming and integration of biodiversity. The underlying problem is that limited capacity in developing countries and transition economies undermines conservation initiatives. Lack of capacity in science, coordination, administration, legislation, and monitoring are barriers to on-ground implementation of biodiversity programmes. Opportunities to overcome these challenges embrace use of knowledge products, information-sharing mechanisms, participatory platforms, educational programmes, multi-level governance, and policy coherence. Innovative market-based instruments are also being trialled in various countries, which seek to offer incentives to local communities. The article concludes that conservation measures should be supported by multiple sectors and secure high level political support. Political, economical, and legislative sectors are more likely to show interest in CBD implementation and use it as a tool for managing biodiversity when they know the Convention processes and perceive it as a benefit. Modest investments in capacity building and training, and engaging different sectors in setting priorities would have a significant pay-off.     

Adaptive Dc-optimal designs for dose finding based on a continuous efficacy endpoint

We introduce a new optimal design for dose finding with a continuous efficacy endpoint. This design is studied in the context of a flexible model for the mean of the dose-response. The design incorporates aspects of both D- and c-optimality and can be used when the study goals under consideration include dose-response estimation, followed by identification of the target dose. Different optimality criteria are considered. Simulations are shown with results comparing our adaptive design to the fixed allocation (without adaptations). We show that both the estimation of dose-response and identification of the minimum effective dose are improved using our design.     

Adaptive decision making in a lymphocyte infusion trial

We describe an adaptive Bayesian design for a clinical trial of an experimental treatment for patients with hematologic malignancies who initially received an allogeneic bone marrow transplant but subsequently suffered a disease recurrence. Treatment consists of up to two courses of targeted immunotherapy followed by allogeneic donor lymphocyte infusion. The immunotherapy is a necessary precursor to the lymphocyte infusion, but it may cause severe liver toxicity and is certain to cause a low white blood cell count and low platelets. The primary scientific goal is to determine the infusion time that has the highest probability of treatment success, defined as the event that the patient does not suffer severe toxicity and is alive with recovered white blood cell count 50 days from the start of therapy. The method is based on a parametric model accounting for toxicity, time to white blood cell recovery, and survival time. The design includes an algorithm for between-patient immunotherapy dose de-escalation based on the toxicity data and an adaptive randomization among five possible infusion times according to their most recent posterior success probabilities. A simulation study shows that the design reliably selects the best infusion time while randomizing greater proportions of patients to superior infusion times.     

Adaptive two-stage analysis of genetic association in case-control designs

We study a two-stage analysis of genetic association for case-control studies. In the first stage, we compare Hardy-Weinberg disequilibrium coefficients between cases and controls and, in the second stage, we apply the Cochran- Armitage trend test. The two analyses are statistically independent when Hardy-Weinberg equilibrium holds in the population, so all the samples are used in both stages. The significance level in the first stage is adaptively determined based on its conditional power. Given the level in the first stage, the level for the second stage analysis is determined with the overall Type I error being asymptotically controlled. For finite sample sizes, a parametric bootstrap method is used to control the overall Type I error rate. This two-stage analysis is often more powerful than the Cochran-Armitage trend test alone for a large association study. The new approach is applied to SNPs from a real study.     

Adaptive designs from the viewpoint of an academic biostatistician

This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'FDA's critical path initiative: A perspective on contributions of biostatistics' by Robert T. O'Neill, 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T. O'Neill, Sue-Jane Wang and John Lawrence; and 'Confirmatory clinical trials with an adaptive design' by Armin Koch.     

Genetic improvement of mammalian fertility: A review of opportunities

The possibility of genetic improvement in the reproductive performance of domestic mammals is introduced. The paper is principally concerned with biological variation and change, but the need to consider economic factors when relating change to improvement is illustrated from time to time. Both male traits, such as semen quality, and female traits, such as litter size, are considered.There is considerable variation among existing populations and the importance of the choice of the most suitable of available populations whether pure or crossbred is emphasized. Variation in litter size is greatest among breeds of sheep (approx. 300%) and least among cattle (only 4%). The possibility that differences in performance may be specific to particular environments and the implications of such an interaction between genotype and environment for the choice of populations are discussed. Among cattle, variation in the incidence of calving difficulties may be marked; it may increase three-fold in cows mated to bulls of a large breed relative to cows mated to bulls of a small breed. Cross-breeding may improve reproductivity by 20%.Once the best population has been chosen, further improvement is dependent on selection within that population. Selection within populations has been rare due to low predicted rates of response. Low selection differentials have probably contributed more to slow responses than have low heritabilities, and recent marked changes achieved by group breeding schemes illustrate what can be done with intense selection.A principal reason for small selection differentials is the inability to measure all reproductive traits in both sexes; one sex has to be chosen at random. The common physiology of reproduction in males and females indicates common genetic control, and the possibility of indirect selection on, say, testis growth to alter ovarian activity is considered along with the use of other physiological selection criteria, including ovulation rate and hormone levels, to increase the rate of response to selection.Finally, the implementation of improvement schemes is discussed. The improvement of reproduction has to be balanced against improvement in other traits such as growth; as the benefits of selection for other traits decline, reproduction would receive greater emphasis. International collaboration to develop strains of extremely high merit for subsequent use by crossbreeding is advocated.     

Early initiation of breastfeeding: a systematic literature review of factors and barriers in South Asia

Background

Early or timely initiation of breastfeeding is crucial in preventing newborn deaths and influences childhood nutrition however remains low in South Asia and the factors and barriers warrant greater consideration for improved action. This review synthesises the evidence on factors and barriers to initiation of breastfeeding within 1 h of birth in South Asia encompassing Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka.

Methods

Studies published between 1990 and 2013 were systematically reviewed through identification in Academic Search Complete, CINAHL, Global Health, MEDLINE and Scopus databases. Twenty-five studies meeting inclusion criteria were included for review. Structured thematic analysis based on leading frameworks was undertaken to understand factors and barriers.

Results

Factors at geographical, socioeconomic, individual, and health-specific levels, such as residence, education, occupation, income, mother’s age and newborn’s gender, and ill health of mother and newborn at delivery, affect early or timely breastfeeding initiation in South Asia. Reported barriers impact through influence on acceptability by traditional feeding practices, priests’ advice, prelacteal feeding and discarding colostrum, mother-in-law’s opinion; availability and accessibility through lack of information, low access to media and health services, and misperception, support and milk insufficiency, involvement of mothers in decision making.

Conclusions

Whilst some barriers manifest similarly across the region some factors are context-specific thus tailored interventions are imperative. Initiatives halting factors and directed towards contextual barriers are required for greater impact on newborn survival and improved nutrition in the South Asia region.

     

Understanding potential barriers and enablers to a perioperative early phase cell therapy trial

Background aimsEarly-phase cell therapy clinical trials depend on patient and physician involvement, yet barriers can impede their participation.MethodsTo optimize engagement for a planned cell therapy trial to prevent perioperative cardiac complications, the authors conducted semi-structured interviews with at-risk patients and physicians who could potentially be involved in the study. The authors used the theoretical domains framework to systematically identify potential barriers and enablers.ResultsForty-one interviews were conducted to reach data saturation, and four overall potential barriers to participation (themes) were identified. Theme 1 emphasizes that patients and physicians need accessible information to better understand the benefits and risks of the novel therapy and trial procedures and to address misconceptions. Theme 2 underscores the need for clarity on whether the trial's primary purpose is safety or efficacy, as this may influence patient and physician decisions. Theme 3 recognizes the resource and logistic realities for patients (e.g., convenient follow-up appointments) and physicians (e.g., personnel to assist in trial procedures, competing priorities). Theme 4 describes the importance of social influences (e.g., physicians and family, peers/colleagues) that may affect decisions to participate and the importance of patient preferences (e.g., availability of physicians to discuss the trial, including caregivers in discussions).ConclusionsProspectively addressing these issues may help optimize feasibility prior to conducting an expensive, resource-intensive trial.