Integration of Translational Research in the European Organization for Research and Treatment of Cancer Research (EORTC) Clinical Trial Cooperative Group Mechanisms

The landscape for cancer research is profoundly different today from that only one decade ago. Basic science is moving rapidly and biotechnological revolutions in molecular targeting and immunology have completely modified the opportunities and concepts for cancer treatment. In contrast to the recent past where cytotoxic molecules were screened in the laboratory and then tested in early clinical studies with toxicity as endpoint instead of the often poorly defined mechanism for its potential anti-tumor effect, we now have entered the age of molecular therapeutics, rationally designed to target "strategic" checkpoints that underlie the malignant phenotype. Translational research in early clinical trials (Phase I and II) is an integral aspect of the development of the new generation of cancer drugs as it is necessary to implement radically different early phase clinical trial design and to validate new biological end-points if the full potential of these new agents is to be realized. The "proof of principle with mechanistic analysis" strategy will allow optimisation of therapy from the beginning, and provide important feedback to pre-clinical drug developers. Translational research is also essential in late (phase III) clinical trials in defining different patient populations that may benefit to differing degrees from new treatments, and thus provide further insight and refine clinical practice in a more and more patient-tailored approach. In this editorial we will discuss the integration of Translational Research in the Organization for Research and Treatment of Cancer (EORTC)

The development of QUADAS : a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

BACKGROUND: In the era of evidence based medicine, with systematic reviews as its cornerstone, adequate quality assessment tools should be available. There is currently a lack of a systematically developed and evaluated tool for the assessment of diagnostic accuracy studies. The aim of this project was to combine empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. METHODS: We conducted a Delphi procedure to develop the quality assessment tool by refining an initial list of items. Members of the Delphi panel were experts in the area of diagnostic research. The results of three previously conducted reviews of the diagnostic literature were used to generate a list of potential items for inclusion in the tool and to provide an evidence base upon which to develop the tool. RESULTS: A total of nine experts in the field of diagnostics took part in the Delphi procedure. The Delphi procedure consisted of four rounds, after which agreement was reached on the items to be included in the tool which we have called QUADAS. The initial list of 28 items was reduced to fourteen items in the final tool. Items included covered patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool is presented together with guidelines for scoring each of the items included in the tool. CONCLUSIONS: This project has produced an evidence based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Further work to determine the usability and validity of the tool continue

An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank.

Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored, partly due to a lack of genotype calling and quality-control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within subpopulations of Great Britain and establish a UK Biobank reference atlas of mtDNA-phenotype associations. A total of 260 mtDNA-phenotype associations were new (P T (MT-ATP6) with type 2 diabetes, rs878966690 /m.13117 A>G (MT-ND5) with multiple sclerosis, 6 mtDNA associations with adult height, 24 mtDNA associations with 2 liver biomarkers and 16 mtDNA associations with parameters of renal function. Rare-variant gene-based tests implicated complex I genes modulating mean corpuscular volume and mean corpuscular hemoglobin. Seven traits had both rare and common mtDNA associations, where rare variants tended to have larger effects than common variants. Our work illustrates the value of studying mtDNA variants in common complex diseases and lays foundations for future large-scale mtDNA association studies

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict

Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo : Bukavu Observ Cohort study results

Background: Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo). Methods: A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization's (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression. Results: The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p < 0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index. Conclusion: This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures