Comparative Haematological Safety Profiles of AT+SP AND AQ+SP for the Treatment of Uncomplicated PlasmodiumFalciparum Malaria in Children

Haematological profiles serve as strong indicators of recovery and the safety of antimalarial drugs in children. The present study evaluated the safety of Artesunate + Sulphadoxine-Pyrimethamine (AT+SP) and Amodiaquine + Sulphadoxine-Pyrimethamine (AQ+SP) combination therapies in the treatment on thirteen different haematological and a biochemical parameters. The study was carried out in malaria holo-endemic settlements in northern Nigeria, among 313 children with uncomplicated Plasmodium falciparum malaria randomly selected, between July and September, 2012 using therapeutic efficacy protocols on antimalarial drugs. There were no cases of lympopenia, and recoveries were faster in AT+SP than AQ+SP for leucocytosis (37.5% vs 17.39%), anaemia (82.23% vs 78.03%), thrombocytopenia (90.13% vs 88.20%), monocytosis (30.92% vs 28.01%) and eosinophilia (31.68%) than AQ+SP (18.01%) in 28 days. Conversely, the recoveries from AQ+SP were higher than AT+SP for neutrophilia (32.89% vs 38.45%), and ALT (76.31% vs 78.33%) over 28 days. In contrast, there were slight adverse effects in both drugs on leucopenia, thrombocytosis, neutropenia, lympocytosis and monocytopenia in the range of 1.97 - 20.50% for AT+SP compared to 3.29 - 11.18% for AQ+SP. Except for monocytopenia, the adverse effects due to AT+SP was higher compared to AQ+SP

Heterogeneity of circulating tumour cell-associated genomic gains in breast cancer and its association with the host immune response.

Tumor cells that preferentially enter circulation include the precursors of metastatic cancer. Previously, we characterized circulating tumor cells (CTC) from patients with breast cancer and identified a signature of genomic regions with recurrent copy-number gains. Through FISH, we now show that these CTC-associated regions are detected within the matched untreated primary tumors of these patients (21% to 69%, median 55.5%, n = 19). Furthermore, they are more prevalent in the metastases of patients who died from breast cancer after multiple rounds of treatment (70% to 100%, median 93%, samples n = 41). Diversity indices revealed that higher spatial heterogeneity for these regions within primary tumors is associated with increased dissemination and metastasis. An identified subclone with multiple regions gained (MRG clone) was enriched in a posttreatment primary breast carcinoma as well as multiple metastatic tumors and local breast recurrences obtained at autopsy, indicative of a distinct early subclone with the capability to resist multiple lines of treatment and eventually cause death. In addition, multiplex immunofluorescence revealed that tumor heterogeneity is significantly associated with the degree of infiltration of B lymphocytes in triple-negative breast cancer, a subtype with a large immune component. Collectively, these data reveal the functional potential of genetic subclones that comprise heterogeneous primary breast carcinomas and are selected for in CTCs and posttreatment breast cancer metastases. In addition, they uncover a relationship between tumor heterogeneity and host immune response in the tumor microenvironment. SIGNIFICANCE: As breast cancers progress, they become more heterogeneous for multiple regions amplified in circulating tumor cells, and intratumoral spatial heterogeneity is associated with the immune landscape

A widespread outbreak of Yersinia pseudotuberculosis O:3 infection from iceberg lettuce

Background. The vehicles and sources of Yersinia pseudotuberculosis infection are unknown. In Finland, clinical microbiology laboratories routinely report Y. pseudotuberculosis isolations and submit isolates for serotype analysis. In October 1998, the number of serotype O:3 infections increased markedly. Methods. Case patients with culture-confirmed Y. pseudotuberculosis O:3 infection were identified by use of laboratory-based surveillance. We conducted a population-based case-control study. Healthy community control subjects were matched by age, sex, and postal code. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). Results. Nationwide, 47 case patients were identified (age range, 277 years; median, 19 years). One patient with bacteremia died; 5 underwent appendectomies. We enrolled 38 case patients and 76 control subjects in the case-control study. Seventy-one percent of case patients and 42% of control subjects reported having eaten iceberg lettuce (matched odds ratio, 3.8; 95% confidence interval, 1.39.4); a dose-response relationship was found for increasing frequency of consumption. Of the 27 isolates obtained from case patients and tested in the analysis, all had indistinguishable PFGE patterns. Four lunch cafeterias that had served iceberg lettuce were associated with clusters of case patients. The lettuce was traced back to originating farms. Conclusions. Iceberg lettuce was implicated as the vehicle of a widespread foodborne Y. pseudotuberculosis outbreak. Ongoing laboratory-based surveillance and serotype analysis were essential in the rapid detection of infection. Cases of yersiniosis, which appear to be sporadic, may be part of unrecognized outbreaks caused by contaminated fresh produce

Research ethics committees: agents of research policy?

The purpose of this commentary is to describe the unintended effects ethics committees may have on research and to analyse the regulatory and administrative problems of clinical trials. DISCUSSION: The Finnish law makes an arbitrary distinction between medical research and other health research, and the European Union's directive for good clinical trials further differentiates drug trials. The starting point of current rules is that clinical trials are lesser in the interest of patients and society than routine health care. However, commercial interests are not considered unethical. The contrasting procedures in research and normal health care may tempt physicians to continue introducing innovations into practice by relying on unsystematic and uncontrolled observations. Tedious and bureaucratic rules may lead to the disappearance of trials initiated by researchers. Trying to accommodate the special legislative requirements for new drug trials into more complex interventions may result in poor designs with unreliable results and increased costs. Meanwhile, current legal requirements may undermine the morale of ethics committee members. CONCLUSION: The aims and the quality of the work of ethics committees should be evaluated, and a reformulation of the EU directive on good clinical trials is needed. Ethical judgement should consider the specific circumstance of each trial, and ethics committees should not foster poor research for legal reasons

DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP)

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS.</p> <p>Methods</p> <p>The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II^-/-), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile.</p> <p>Results</p> <p>PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice.</p> <p>Conclusions</p> <p>While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.</p

Mobile Phones and Social Signal Processing for Analysis and Understanding of Dyadic Conversations

Social Signal Processing is the domain aimed at bridging the social intelligence gap between humans and machines via modeling, analysis and synthesis of nonverbal behavior in social interactions. One of the main challenges of the domain is to sense unobtrusively the behavior of social interaction participants, one of the key conditions to preserve the spontaneity and naturalness of the interactions under exam. In this respect, mobile devices offer a major opportunity because they are equipped with a wide array of sensors that, while capturing the behavior of their users with an unprecedented depth, are still invisible. This is particularly important because mobile devices are part of the everyday life of a large number of individuals and, hence, they can be used to investigate and sense natural and spontaneous scenarios

Evaluation of the selfitis behavior scale across two Persian-speaking countries, Iran and Afghanistan: advanced psychometric testing in a large-scale sample

Selfitis—which started off as a hoax but has now been investigated empirically—has been defined as the obsessive–compulsive desire to take photos of oneself and post them on social media. Furthermore, a scale to assess selfitis, the Selfitis Behavior Scale (SBS), has been developed. This study applied advanced psychometric testing methods, including confirmatory factor analysis (utilizing classical test theory) and the Rasch model (utilizing modern test theory), to examine the psychometric properties among Persian speakers (in Iran and Afghanistan). The participants (3163 Iranians and 1100 Afghanistani) completed an online survey posted on Instagram pages. The SBS showed promising properties, including satisfactory reliability (e.g., internal consistency and test–retest reliability), excellent construct validity (e.g., good fit in the CFA and Rasch models), and acceptable measurement invariance across Iranian and Afghan samples. Consequently, the SBS is a valid and reliable instrument for assessing selfitis among Persian-speaking samples