2304899
Controlling for confounding variables in MS-omics protocol: why modularity matters
As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation.
15927414
LC-MS alignment in theory and practice: a comprehensive algorithmic review
Liquid chromatography-mass spectrometry is widely used for comparative replicate sample analysis in proteomics, lipidomics and metabolomics. Before statistical comparison, registration must be established to match corresponding analytes from run to run. Alignment, the most popular correspondence approach, consists of constructing a function that warps the content of runs to most closely match a given reference sample. To date, dozens of correspondence algorithms have been proposed, creating a daunting challenge for practitioners in algorithm selection. Yet, existing reviews have highlighted only a few approaches. In this review, we describe 50 correspondence algorithms to facilitate practical algorithm selection. We elucidate the motivation for correspondence and analyze the limitations of current approaches, which include prohibitive runtimes, numerous user parameters, model limitations and the need for reference samples. We suggest and describe a paradigm shift for overcoming current correspondence limitations by building on known liquid chromatography-mass spectrometry behavior.
27343241
Novel algorithms and the benefits of comparative validation
Contact: 2robsmith@gmail.com, jtprince@chem.byu.edu Bioinformatic research has produced a large volume of proposed algorithmic solutions to a host of problems. Whether presented as a processing step in a clinical experiment or treated in a stand-alone publication, novel bioinformatic algorithms are often not subjected to the thorough comparative evaluation endured by their counterparts in other closely related fields—such as computer science—where an algorithm unevaluated against extant methods is considered unpublishable. Two audiences are interested in algorithmic publications: the practitioner, who may use the algorithm, and the researcher, who will work to develop solutions superior to those extant. We argue that failure during the review/publication process to require comparative evaluation for novel algorithms is detrimental to both parties. To demonstrate the dilemma, we conducted a case study of novel LC-MS alignment algorithms. Of the 48 publications from 2001 to 2012 that present alignment algorithms of which we are aware, 60% include no comparison to other methods. Another 20%
3424059
Alterations in the hypothalamic pituitary adrenal axis during pregnancy and the placental clock that determines the length of parturition.
Although corticotrophin releasing hormone (CRH) was initially identified as a hypothalamic peptide it is also synthesised in the placenta and secreted into both the maternal and fetal circulation. The presence of large molecular weight forms in the placenta suggest that secretion may be constitutive rather that regulated. Placental CRH is bioactive but causes only modest increases in ACTH and cortisol in the pregnant woman because of agonist induced desensitisation of pituitary CRH receptors. CRH concentrations increase exponentially in maternal plasma as gestation advances. Elevated concentrations, compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve describing the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates indicating that CRH is linked to a placental clock which determines the length of gestation. Maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may prevent preterm labour. As significant CRH production by the placenta is restricted to primates future research must take into account the species specificity of the mechanisms regulating parturition.
16842490
Appealing to altruism: an alternative strategy to address the health workforce crisis in developing countries?
BACKGROUND
Recruitment and retention of health workers is a major concern. Policy initiatives emphasize financial incentives, despite mixed evidence of their effectiveness. Qualitative studies suggest that nurses especially may be more driven by altruistic motivations, but quantitative research has overlooked such values. This paper adds to the literature through characterizing the nature and determinants of nurses' altruism, based on a cross-country quantitative study.


METHODS
An experimental 'dictator game' was undertaken with 1064 final year nursing students in Kenya, South Africa and Thailand between April 2007 and July 2008. This presents participants with a real financial endowment to split between themselves and another student, a patient or a poor person. Giving a greater share of this financial endowment to the other person is interpreted as reflecting greater altruism.


RESULTS
Nursing students gave over 30% of their initial endowment to others (compared with 10% in similar experiments undertaken in other samples). Respondents in all three countries showed greater generosity to patients and the poor than to fellow students.


CONCLUSIONS
Consideration needs to be given to how to appeal to altruistic values as an alternative strategy to encourage nurses to enter the profession and remain, such as designing recruitment strategies to increase recruitment of altruistic individuals who are more likely to remain in the profession.
1484363
Public health evaluation in the twenty-first century: time to see the wood as well as the trees.
This paper argues that concepts, methodologies and practices within public health need further development if they are to be sufficient to allow us to develop, undertake and evaluate interventions in the twenty-first century. The public health profession, and the disciplines that contribute to it, maintains the historical focus upon detailed micro analysis (individual and health sector) and not broader macro analysis (societal and system). This brief paper suggests why this is and outlines three challenges it poses: specifying and evaluating outcomes; specifying and understanding complex causal pathways in social interventions and the development of multisector evaluation, to meet information demands from multiple stakeholders. While there is general agreement that public health evaluation needs development, this paper argues that the focus needs to be more upon a broader evaluative space than is currently practiced. There is a need to move beyond primary and secondary health-related effects upon individuals, and focus more on evaluation of the wider range and distribution of direct and indirect effects upon individuals, communities and populations. That is, those involved in public health evaluation need to step back and first consider the wood before focusing in on specific trees.
29843044
Hormone trajectories leading to human birth
The mechanisms regulating human parturition and labor remain unknown. This ignorance is expensive as preterm birth is responsible for 70% of neonatal mortality and 50% of cerebral palsy. Methods for the prediction of preterm birth and treatments for women in preterm labor have poor efficacy reflecting our limited knowledge of the mechanisms involved. Recent research has supported the view that parturition is a cascade of events that commences early in pregnancy and involves the mother, fetus, placenta, membranes, cervix and myometrium. Although a number of the key hormones and proteins involved have been identified, the relationships between these factors in time and tissues remain unclear. Placental production of Corticotropin-releasing hormone (CRH) is proposed as an early event regulating the cascade of events. Central to the onset of parturition will be a mechanism for progesterone withdrawal and estrogen activation in human. Two forms of progesterone receptor with opposing actions exist in the human myometrium. Progesterone receptor A (PR-A) is a dominant negative repressor of progesterone receptor B (PR-B). Preliminary studies strongly support the hypothesis that the onset of human parturition is initiated by rising concentrations of PR-A in the myometrium.
36391510
Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations
In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.