A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. The basic tenet behind meta-analyses is that there is a common truth behind all conceptually similar scientific studies, but, measured with a certain error within individual studies; the aim is to use approaches from statistics to derive a pooled estimate closest to the unknown common truth based on how this error is perceived. In essence, all existing methods yield a weighted average from the results of the individual studies and what differs is the manner in which these weights are allocated and the manner in which the uncertainty is computed around the point estimate thus generated. In addition to providing an estimate of the unknown common truth, meta-analysis has the capacity to contrast results from different studies and identify patterns among study results, sources of disagreement among those results, or other interesting relationships that may come to light in the context of multiple studies.
A key benefit of this approach is the aggregation of information leading to a higher statistical power and more robust point estimate than is possible from the measure derived from any individual study. However, in performing a meta-analysis, an investigator must make choices which can affect the results, including deciding how to search for studies, selecting studies based on a set of objective criteria, dealing with incomplete data, analyzing the data, accounting for or choosing not to account for publication bias. Meta-analyses are but not always, important components of a systematic review procedure. For instance, a meta-analysis may be conducted on several clinical trials of a medical treatment, in an effort to obtain a better understanding of how well the treatment works. Here it is convenient to follow the terminology used by the Cochrane Collaboration, use "meta-analysis" to refer to statistical methods of combining evidence, leaving other aspects of'research synthesis' or'evidence synthesis', such as combining information from qualitative studies, for the more general context of systematic reviews.
A meta-analysis is a secondary source. The historical roots of meta-analysis can be traced back to 17th century studies of astronomy, while a paper published in 1904 by the statistician Karl Pearson in the British Medical Journal which collated data from several studies of typhoid inoculation is seen as the first time a meta-analytic approach was used to aggregate the outcomes of multiple clinical studies; the first meta-analysis of all conceptually identical experiments concerning a particular research issue, conducted by independent researchers, has been identified as the 1940 book-length publication Extrasensory Perception After Sixty Years, authored by Duke University psychologists J. G. Pratt, J. B. Rhine, associates; this encompassed a review of 145 reports on ESP experiments published from 1882 to 1939, included an estimate of the influence of unpublished papers on the overall effect. Although meta-analysis is used in epidemiology and evidence-based medicine today, a meta-analysis of a medical treatment was not published until 1955.
In the 1970s, more sophisticated analytical techniques were introduced in educational research, starting with the work of Gene V. Glass, Frank L. Schmidt and John E. Hunter; the term "meta-analysis" was coined in 1976 by the statistician Gene V. Glass, who stated "my major interest is in what we have come to call...the meta-analysis of research. The term is a bit grand, but it is precise and apt... Meta-analysis refers to the analysis of analyses". Although this led to him being recognized as the modern founder of the method, the methodology behind what he termed "meta-analysis" predates his work by several decades; the statistical theory surrounding meta-analysis was advanced by the work of Nambury S. Raju, Larry V. Hedges, Harris Cooper, Ingram Olkin, John E. Hunter, Jacob Cohen, Thomas C. Chalmers, Robert Rosenthal, Frank L. Schmidt, Douglas G. Bonett. Conceptually, a meta-analysis uses a statistical approach to combine the results from multiple studies in an effort to increase power, improve estimates of the size of the effect and/or to resolve uncertainty when reports disagree.
A meta-analysis is a statistical overview of the results from one or more systematic reviews. It produces a weighted average of the included study results and this approach has several advantages: Results can be generalized to a larger population The precision and accuracy of estimates can be improved as more data is used. This, in turn, may increase the statistical power to detect an effect Inconsistency of results across studies can be quantified and analyzed. For instance, inconsistency may arise from sampling error, or study results influenced by differences between study protocols Hypothesis testing can be applied on summary estimates Moderators can be included to explain variation between studies The presence of publication bias can be investigated A meta-analysis of several small studies does not predict the results of a single large study; some have argued that a weakness of the method is that sources of bias are not controlled by the method: a good meta-analysis cannot correct for poor design or bias in the original studies.
This would mean that only methodologically sound studies should be included in a meta-analysis, a practice called'best evidence synthesis'. Other meta-analysts would include weaker studies, add a study-level predictor variable that reflects the methodological quality of the studies to examine the effect of study quality on the effect size. However, others have argued that a better approach is to preserve information about the variance in the study sample, casting as wide a net as
Chromium is a chemical element with symbol Cr and atomic number 24. It is the first element in group 6, it is a steely-grey, lustrous and brittle transition metal. Chromium boasts a high usage rate as a metal, able to be polished while resisting tarnishing. Chromium is the main additive in stainless steel, a popular steel alloy due to its uncommonly high specular reflection. Simple polished chromium reflects 70% of the visible spectrum, with 90% of infrared light being reflected; the name of the element is derived from the Greek word χρῶμα, chrōma, meaning color, because many chromium compounds are intensely colored. Ferrochromium alloy is commercially produced from chromite by silicothermic or aluminothermic reactions and chromium metal by roasting and leaching processes followed by reduction with carbon and aluminium. Chromium metal is of high value for hardness. A major development in steel production was the discovery that steel could be made resistant to corrosion and discoloration by adding metallic chromium to form stainless steel.
Stainless steel and chrome plating together comprise 85% of the commercial use. In the United States, trivalent chromium ion is considered an essential nutrient in humans for insulin and lipid metabolism. However, in 2014, the European Food Safety Authority, acting for the European Union, concluded that there was not sufficient evidence for chromium to be recognized as essential. While chromium metal and Cr ions are not considered toxic, hexavalent chromium is both toxic and carcinogenic. Abandoned chromium production sites require environmental cleanup. Chromium is the fourth transition metal found on the periodic table, has an electron configuration of 3d5 4s1, it is the first element in the periodic table whose ground-state electron configuration violates the Aufbau principle. This occurs again in the periodic table with other elements and their electron configurations, such as copper and molybdenum; this occurs. In the previous elements, the energetic cost of promoting an electron to the next higher energy level is too great to compensate for that released by lessening inter-electronic repulsion.
However, in the 3d transition metals, the energy gap between the 3d and the next-higher 4s subshell is small, because the 3d subshell is more compact than the 4s subshell, inter-electron repulsion is smaller between 4s electrons than between 3d electrons. This lowers the energetic cost of promotion and increases the energy released by it, so that the promotion becomes energetically feasible and one or two electrons are always promoted to the 4s subshell. Chromium is the first element in the 3d series where the 3d electrons start to sink into the inert core. Chromium is a strong oxidising agent in contrast to the tungsten oxides. Chromium is hard, is the third hardest element behind carbon and boron, its Mohs hardness is 8.5, which means that it can scratch samples of quartz and topaz, but can be scratched by corundum. Chromium is resistant to tarnishing, which makes it useful as a metal that preserves its outermost layer from corroding, unlike other metals such as copper and aluminium. Chromium has a melting point of 1907 °C, low compared to the majority of transition metals.
However, it still has the second highest melting point out of all the Period 4 elements, being topped by vanadium by 3 °C at 1910 °C. The boiling point of 2671 °C, however, is comparatively lower, having the third lowest boiling point out of the Period 4 transition metals alone behind manganese and zinc. Chromium has an unusually high specular reflection in comparison to that of other transition metals. At 425 μm, chromium was found to have a relative maximum reflection of about 72% reflectance, before entering a depression in reflectivity, reaching a minimum of 62% reflectance at 750 μm before rising again to reflecting 90% of 4000 μm of infrared waves.. When chromium is formed into a stainless steel alloy and polished, the specular reflection decreases with the inclusion of additional metals, yet is still rather high in comparison with other alloys. Between 40% and 60% of the visible spectrum is reflected from polished stainless steel; the explanation on why chromium displays such a high turnout of reflected photon waves in general the 90% of infrared waves that were reflected, can be attributed to chromium's magnetic properties.
Chromium has unique magnetic properties in the sense that chromium is the only elemental solid which shows antiferromagnetic ordering at room temperature. Above 38 °C, its magnetic ordering changes to paramagnetic.. The antiferromagnetic properties, which cause the chromium atoms to temporarily ionize and bond with themselves, are present because the body-centric cubic's magnetic properties are disproportionate to the lattice periodicity; this is due to the fact that the magnetic moments at the cube's corners and the cube centers are not equal, but are still antiparallel. From here, the frequency-dependent relative permittivity of chromium, deriving from Maxwell's equations in conjunction with chromium's antiferromagnetivity, leaves chromium with a high infrared and visible light reflectance. Chromium metal left standing in air is passivated by oxidation, forming a th
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment which aims to reduce bias when testing a new treatment. The people participating in the trial are randomly allocated to either the group receiving the treatment under investigation or to a group receiving standard treatment as the control. Randomization minimises selection bias and the different comparison groups allow the researchers to determine any effects of the treatment when compared with the no treatment group, while other variables are kept constant; the RCT is considered the gold standard for a clinical trial. RCTs are used to test the efficacy or effectiveness of various types of medical intervention and may provide information about adverse effects, such as drug reactions. Random assignment of intervention is done after subjects have been assessed for eligibility and recruited, but before the intervention to be studied begins. Random allocation in real trials is complex. After randomization, the two groups of subjects are followed in the same way and the only differences between them is the care they receive.
For example, in terms of procedures, outpatient visits, follow-up calls, should be those intrinsic to the treatments being compared. The most important advantage of proper randomization is that it minimizes allocation bias, balancing both known and unknown prognostic factors, in the assignment of treatments; the terms "RCT" and randomized trial are sometimes used synonymously, but the methodologically sound practice is to reserve the "RCT" name only for trials that contain control groups, in which groups receiving the experimental treatment are compared with control groups receiving no treatment or a tested treatment. The term "randomized trials" omits mention of controls and can describe studies that compare multiple treatment groups with each other. Although the "RCT" name is sometimes expanded as "randomized clinical trial" or "randomized comparative trial", the methodologically sound practice, to avoid ambiguity in the scientific literature, is to retain "control" in the definition of "RCT" and thus reserve that name only for trials that contain controls.
Not all randomized clinical trials are randomized controlled trials. The term randomized controlled clinical trials is a methodologically sound alternate expansion for "RCT" in RCTs that concern clinical research; the first reported clinical trial was conducted by James Lind in 1747 to identify treatment for scurvy. Randomized experiments appeared in psychology, where they were introduced by Charles Sanders Peirce, in education. Randomized experiments appeared in agriculture, due to Jerzy Neyman and Ronald A. Fisher. Fisher's experimental research and his writings popularized randomized experiments; the first published RCT in medicine appeared in the 1948 paper entitled "Streptomycin treatment of pulmonary tuberculosis", which described a Medical Research Council investigation. One of the authors of that paper was Austin Bradford Hill, credited as having conceived the modern RCT. By the late 20th century, RCTs were recognized as the standard method for "rational therapeutics" in medicine; as of 2004, more than 150,000 RCTs were in the Cochrane Library.
To improve the reporting of RCTs in the medical literature, an international group of scientists and editors published Consolidated Standards of Reporting Trials Statements in 1996, 2001 and 2010, these have become accepted. Randomization is the process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce the bias. Although the principle of clinical equipoise common to clinical trials has been applied to RCTs, the ethics of RCTs have special considerations. For one, it has been argued. For another, "collective equipoise" can conflict with a lack of personal equipoise. Zelen's design, used for some RCTs, randomizes subjects before they provide informed consent, which may be ethical for RCTs of screening and selected therapies, but is unethical "for most therapeutic trials."Although subjects always provide informed consent for their participation in an RCT, studies since 1982 have documented that RCT subjects may believe that they are certain to receive treatment, best for them personally.
Further research is necessary to determine the prevalence of and ways to address this "therapeutic misconception". The RCT method variations may create cultural effects that have not been well understood. For example, patients with terminal illness may join trials in the hope of being cured when treatments are unlikely to be successful. In 2004, the International Committee of Medical Journal Editors announced that all trials starting enrolment after July 1, 2005 must be registered prior to consideration for publication in one of the 12 member journals of the committee. However, trial registration may still occur not at all. Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication. One way
Chromium picolinate is a chemical compound sold as a nutritional supplement to treat type 2 diabetes and promote weight loss. This bright-red coordination compound is derived from picolinic acid. Small quantities of chromium are needed for glucose utilization by insulin in normal health, but deficiency is rare and has only been observed in people receiving 100% of their nutrient needs intravenously, i.e. total parenteral nutrition diets. Chromium has been identified as regulating insulin by increasing the sensitivity of the insulin receptor; as such, chromium picolinate has been proposed as a treatment for type 2 diabetes, although its effectiveness remains controversial due to conflicting evidence from human trials. A study in 1989 suggested that chromium picolinate may assist in weight loss and increase muscle mass which led to an increase in the usage of chromium picolinate supplements, resulting in it being for a while the second most used supplement behind calcium. A 2013 Cochrane review was unable to find "reliable evidence to inform firm decisions" to support such claims.
Research has shown that it improves insulin sensitivity by either prolonging its activity or up-regulating the production of mRNA to produce more insulin receptors. Amongst the transition metals, Cr3+ is the most controversial in terms of nutritional value and toxicity; this controversy centers on. Furthermore, this controversy is amplified by the fact that no Cr-containing biomolecules have had their structure characterized, nor has the mode of action been determined; the first experiment that led to the discovery of Cr3+ playing a role in glucose metabolism proposed that the biologically active form of the metal existed in a protein called glucose tolerance factor, new evidence suggests that it is an artifact obtained from isolation procedures. The only accepted indicator of chromium deficiency is the reversal of symptoms that occurs when chromium supplementation is administered to people on total parenteral nutrition. Chromium picolinate is a pinkish-red compound and was first reported in 1917.
It is poorly soluble in water, having a solubility of 600 µM in water at near neutral pH. Similar to other chromium compounds, it is inert and unreactive, meaning that this complex is stable at ambient conditions and high temperatures are required to decompose the compound. At lower pH levels, the complex hydrolyzes to release picolinic acid and free Cr3+. Chromium picolinate has a distorted octahedral geometry and is isostructural to cobalt and manganese counterparts. Chromium is a hard lewis acid and as such has high affinity to the carboxylate oxygen and medium affinity to the pyridine nitrogen of picolinate; each picolinate ligand acts as a bidentate chelating agent and neutralizes the +3 charge of Cr3+. Evidence that the Cr3+ center coordinates to the pyridine nitrogen comes from a shift in the IR spectra of a C=N vibration at 1602.4 cm−1 for free picolinic acid to 1565.9 cm−1 for chromium picolinate. The bond length between Cr3+ and the nitrogen atom of the pyridine ring on picoliante ranges from 2.047 to 2.048 Å.
The picolinate ligand coordinates to Cr3+ only when deprotonated and this is evident by the disappearance of IR bands ranging from 2400–2800 cm−1 and 1443 cm−1, corresponding to the O-H stretching and bending on the carboxyl functional group. Furthermore, this IR shift indicates that only one oxygen atom from the carboxylate of picolinate coordinates to the Cr3+ center; the Cr-O bond length ranges from 1.949 to 1.957 Å. The crystal structure has only been described in 2013. Water does not coordinate to the Cr3+ center and is instead thought to hydrogen bond between other Cr3 complexes to form a network of Cr3 complexes. Chromium has been identified as an essential nutrient in maintaining normal blood glucose levels and as such, it is proposed to interact with two occurring molecules found within the body; these interactions are most to occur through coordination with hard ligands such as aspartate and glutamate, as Cr itself is a hard metal. Once chromium picolinate is ingested and enters the stomach, acidic hydrolysis of the complex occurs when in contact with the stomach mucosa.
The hydrolyzed Cr3+ is present in the hexaaqua form and polymerizes to form an insoluble Cr-hydroxide-oxide once it reaches the alkaline pH of the small intestine. 2% of Cr3+ is absorbed through the gut as chromium picolinate via unsaturated passive transport. Although absorption is low, CrPic3 absorbs more efficiently than other organic and inorganic sources and thus accumulate at higher concentrations in tissues; this has been one major selling point for chromium picolinate over other chromium supplements. Organic sources tend to absorb better as they have ligands which are more lipophilic and neutralize the charge of the metal, thus permitting for easier passage through the intestinal membrane, it has been shown that dietary factors affect Cr3+ absorption. Starch, simple sugars, oxalic acid, some amino acids tend to increase the rate of absorption of chromium; this is a result of ligand chelation. In contrast, magnesium, zinc and iron reduce the rate of absorption; these ions introduce new metal-ligand equilibria, thus decreasing the lipophilic ligand pool available to Cr3+.
Once absorbed into the bloodstream, 80% of the Cr3+ from CrPic3 is passed along to transferrin. The exact mechanism of release is unknown, however, it is beli
European Food Safety Authority
The European Food Safety Authority is the agency of the European Union that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, is based in Parma and has a budget for 2016 of €79.5 million, a total staff of 447. The work of EFSA covers all matters with a direct or indirect impact on food and feed safety, including animal health and welfare, plant protection and plant health and nutrition. EFSA supports the European Commission, the European Parliament and EU member states in taking effective and timely risk management decisions that ensure the protection of the health of European consumers and the safety of the food and feed chain. EFSA communicates to the public in an open and transparent way on all matters within its remit. Based on a regulation of 2002, the EFSA is composed of four bodies: Management Board Executive Director Advisory Forum Scientific Committee and Scientific PanelsThe Management Board sets the budget, approves work programmes, is responsible for ensuring that EFSA co-operates with partner organisations across the EU and beyond.
It is composed of fourteen members appointed by the Council of the European Union in consultation with the European Parliament from a list drawn up by the European Commission, plus one representative of the European Commission. The Executive Director is EFSA's legal representative and is responsible for day-to-day administration and implementing work programmes, implementing other decisions adopted by the Management Board, they are appointed by the Management Board. The Advisory Forum advises the Executive Director, in particular in drafting a proposal for the EFSA's work programmes, it is composed of representatives of national bodies responsible for risk assessment in the Member States, with observers from Norway, Iceland and the European Commission. The Scientific Committee and its Scientific Panels provide scientific opinions and advice, each within their own sphere of competence, are composed of independent scientific experts; the number and names of the Scientific Panels are adapted in the light of technical and scientific development by the European Commission at EFSA's request.
The independent scientific experts are appointed by the Management Board upon a proposal from the Executive Director for three-year terms. The EFSA cooperates with the national food safety authorities of the 28 EU member states and Norway, as well as observers from Switzerland and EU candidate countries, through its Focal Points, who communicate with research institutes and other stakeholders. They'assist in the exchange of scientific information and experts, advise on cooperation activities and scientific projects, promote training in risk assessment and raise EFSA’s scientific visibility and outreach in Member States.' The following countries' national food safety authorities are members of the EFSA Focal Point network: The following countries' national food safety authorities are observers of the EFSA Focal Point network: The scientific output of the European Food Safety Authority is published in the EFSA Journal, an open-access, online scientific journal. This concerns risk assessment in relation to food and feed and includes nutrition, animal health and welfare, plant health and plant protection.
EFSA has been criticised for their alleged overregulation, as well as allegations of "frequent conflicts of interest", some of them undeclared. EFSA has been criticised by the NGO CHEM Trust for misrepresenting the results of their expert committee's report on Bisphenol A in January 2015. EFSA claimed in the abstract, press release and briefing that Bisphenol A'posed no risk' to health, when the expert report stated the risk was'low' when considering aggregate exposure. EFSA modified the abstract to correct this error, though the press release remains unchanged. EFSA have argued that use of'no health concern' in their press release and Bisphenol A briefing is to ensure these materials are accessible, though this rationale is disputed by CHEM Trust. Agriculture and Fisheries Council Directorate-General for Agriculture, Social Affairs and Health Employment, Social Policy and Consumer Affairs Council EU-Eco-regulation European Commissioner for Health Directorate-General for Health and Consumers European Parliament Committee on the Environment, Public Health and Food Safety Health mark List of food safety organisations Rapid Alert System for Food and Feed Regulation of genetically modified organisms in the European Union The European Consumer Organisation Media related to European Food Safety Authority at Wikimedia Commons Official website Health-EU public health portal of the Directorate-General for Health and Consumers EFSA Journal