Unsafe abortion: the preventable pandemic Grimes, David A; Benson, Janie; Singh, Susheela ...
The Lancet (British edition),
11/2006, Letnik:
368, Številka:
9550
Journal Article
Recenzirano
Ending the silent pandemic of unsafe abortion is an urgent public-health and human-rights imperative. As with other more visible global-health issues, this scourge threatens women throughout the ...developing world. Every year, about 19–20 million abortions are done by individuals without the requisite skills, or in environments below minimum medical standards, or both. Nearly all unsafe abortions (97%) are in developing countries. An estimated 68 000 women die as a result, and millions more have complications, many permanent. Important causes of death include haemorrhage, infection, and poisoning. Legalisation of abortion on request is a necessary but insufficient step toward improving women's health; in some countries, such as India, where abortion has been legal for decades, access to competent care remains restricted because of other barriers. Access to safe abortion improves women's health, and vice versa, as documented in Romania during the regime of President Nicolae Ceausescu. The availability of modern contraception can reduce but never eliminate the need for abortion. Direct costs of treating abortion complications burden impoverished health care systems, and indirect costs also drain struggling economies. The development of manual vacuum aspiration to empty the uterus, and the use of misoprostol, an oxytocic agent, have improved the care of women. Access to safe, legal abortion is a fundamental right of women, irrespective of where they live. The underlying causes of morbidity and mortality from unsafe abortion today are not blood loss and infection but, rather, apathy and disdain toward women.
Proper randomisation rests on adequate allocation concealment. An allocation concealment process keeps clinicians and participants unaware of upcoming assignments. Without it, even properly developed ...random allocation sequences can be subverted. Within this concealment process, the crucial unbiased nature of randomised controlled trials collides with their most vexing implementation problems. Proper allocation concealment frequently frustrates clinical inclinations, which annoys those who do the trials. Randomised controlled trials are anathema to clinicians. Many involved with trials will be tempted to decipher assignments, which subverts randomisation. For some implementing a trial, deciphering the allocation scheme might frequently become too great an intellectual challenge to resist. Whether their motives indicate innocent or pernicious intents, such tampering undermines the validity of a trial. Indeed, inadequate allocation concealment leads to exaggerated estimates of treatment effect, on average, but with scope for bias in either direction. Trial investigators will be crafty in any potential efforts to decipher the allocation sequence, so trial designers must be just as clever in their design efforts to prevent deciphering. Investigators must effectively immunise trials against selection and confounding biases with proper allocation concealment. Furthermore, investigators should report baseline comparisons on important prognostic variables. Hypothesis tests of baseline characteristics, however, are superfluous and could be harmful if they lead investigators to suppress reporting any baseline imbalances.
Blinding embodies a rich history spanning over two centuries. Most researchers worldwide understand blinding terminology, but confusion lurks beyond a general comprehension. Terms such as single ...blind, double blind, and triple blind mean different things to different people. Moreover, many medical researchers confuse blinding with allocation concealment. Such confusion indicates misunderstandings of both. The term blinding refers to keeping trial participants, investigators (usually health-care providers), or assessors (those collecting outcome data) unaware of the assigned intervention, so that they will not be influenced by that knowledge. Blinding usually reduces differential assessment of outcomes (information bias), but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment (sometimes called co-intervention). Many investigators and readers naively consider a randomised trial as high quality simply because it is double blind, as if double-blinding is the sine qua non of a randomised controlled trial. Although double blinding (blinding investigators, participants, and outcome assessors) indicates a strong design, trials that are not double blinded should not automatically be deemed inferior. Rather than solely relying on terminology like double blinding, researchers should explicitly state who was blinded, and how. We recommend placing greater credence in results when investigators at least blind outcome assessments, except with objective outcomes, such as death, which leave little room for bias. If investigators properly report their blinding efforts, readers can judge them. Unfortunately, many articles do not contain proper reporting. If an article claims blinding without any accompanying clarification, readers should remain sceptical about its effect on bias reduction.
The ability to reliably and reproducibly measure any protein of the human proteome in any tissue or cell type would be transformative for understanding systems-level properties as well as specific ...pathways in physiology and disease. Here, we describe the generation and verification of a compendium of highly specific assays that enable quantification of 99.7% of the 20,277 annotated human proteins by the widely accessible, sensitive, and robust targeted mass spectrometric method selected reaction monitoring, SRM. This human SRMAtlas provides definitive coordinates that conclusively identify the respective peptide in biological samples. We report data on 166,174 proteotypic peptides providing multiple, independent assays to quantify any human protein and numerous spliced variants, non-synonymous mutations, and post-translational modifications. The data are freely accessible as a resource at http://www.srmatlas.org/, and we demonstrate its utility by examining the network response to inhibition of cholesterol synthesis in liver cells and to docetaxel in prostate cancer lines.
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•Human SRMAtlas: 166,174 proteotypic peptides representing the human proteome•Resource of verified high-resolution spectra and multiplexed SRM assays•Supports proteome-scale quantification as well as hypothesis-driven research•Web database with free unlimited access
This resource enables the accurate detection and quantification of any known or predicted human protein from complex biological samples.
Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing ...child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Use of control (comparison) groups is a powerful research tool. In case-control studies, controls estimate the frequency of an exposure in the population under study. Controls can be taken from known ...or unknown study populations. A known group consists of a defined population observed over a period, such as passengers on a cruise ship. When the study group is known, a sample of the population can be used as controls. If no population roster exists, then techniques such as random-digit dialling can be used. Sometimes, however, the study group is unknown, for example, motor-vehicle crash victims brought to an emergency department, who may come from far away. In this situation, hospital controls, neighbourhood controls, and friend, associate, or relative controls can be used. In general, one well-selected control group is better than two or more. When the number of cases is small, the ratio of controls to cases can be raised to improve the ability to find important differences. Although no ideal control group exists, readers need to think carefully about how representative the controls are. Poor choice of controls can lead to both wrong results and possible medical harm.
In the absence of surgical care, case-fatality rates are high for common, easily treatable conditions including appendicitis, hernia, fractures, obstructed labour, congenital anomalies, and breast ...and cervical cancer. The provision of safe and affordable surgical and anaesthesia care when needed not only reduces premature death and disability, but also boosts welfare, economic productivity, capacity, and freedoms, contributing to long-term development.
Proper randomisation means little if investigators cannot include all randomised participants in the primary analysis. Participants might ignore follow-up, leave town, or take aspartame when ...instructed to take aspirin. Exclusions before randomisation do not bias the treatment comparison, but they can hurt generalisability. Eligibility criteria for a trial should be clear, specific, and applied before randomisation. Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested. In principle, assessment of exclusions after randomisation is simple: none are allowed. For the primary analysis, all participants enrolled should be included and analysed as part of the original group assigned (an intent-to-treat analysis). In reality, however, losses frequently occur. Investigators should, therefore, commit adequate resources to develop and implement procedures to maximise retention of participants. Moreover, researchers should provide clear, explicit information on the progress of all randomised participants through the trial by use of, for instance, a trial profile. Investigators can also do secondary analyses on, for instance, per-protocol or as-treated participants. Such analyses should be described as secondary and non-randomised comparisons. Mishandling of exclusions causes serious methodological difficulties. Unfortunately, some explanations for mishandling exclusions intuitively appeal to readers, disguising the seriousness of the issues. Creative mismanagement of exclusions can undermine trial validity.
Combination contraceptives: effects on weight Gallo, Maria F; Lopez, Laureen M; Grimes, David A ...
Cochrane database of systematic reviews,
01/2014, Letnik:
2014, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit ...the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established.
Objectives
The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight.
Search methods
In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search.
Selection criteria
All English‐language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length.
Data collection and analysis
All titles and s located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post‐treatment measurements using a fixed‐effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated.
Main results
We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied.
Authors' conclusions
Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non‐hormonal group to control for other factors, including changes in weight over time.
Akt/PKB is a serine/threonine kinase that promotes tumor cell growth by phosphorylating transcription factors and cell cycle proteins. There is particular interest in finding tumor-specific ...substrates for Akt to understand how this protein functions in cancer and to provide new avenues for therapeutic targeting. Our laboratory sought to identify novel Akt substrates that are expressed in breast cancer. In this study, we determined that activated Akt is positively correlated with the protein expression of the transcription/translation factor Y-box binding protein-1 (YB-1) in primary breast cancer by screening tumor tissue microarrays. We therefore questioned whether Akt and YB-1 might be functionally linked. Herein, we illustrate that activated Akt binds to and phosphorylates the YB-1 cold shock domain at Ser102. We then addressed the functional significance of disrupting Ser102 by mutating it to Ala102. Following the stable expression of Flag:YB-1 and Flag:YB-1 (Ala102) in MCF-7 cells, we observed that disruption of the Akt phosphorylation site on YB-1 suppressed tumor cell growth in soft agar and in monolayer. This correlated with an inhibition of nuclear translocation by the YB-1(Ala102) mutant. In conclusion, YB-1 is a new Akt substrate and disruption of this specific site inhibits tumor cell growth.
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