What will be the Surprises for HRD in 2018? A Futures Scenario

The paper reports findings from a futures workshop to consider surprises — unexpected or astonishing events or facts — that may await HRD. Participants were asked to identify an HRD issue for the future and then pose questions that placed surprise up front and that could indicate a vulnerability for HRD. Two scenarios are developed for the year 2028 and events leading to this year. In the first, S1, human behaviour within organizations is defined by machines and machines prescribe why, what and where work is needed, who does it, when, and how work is done. Thus programmes of learning are pre-determined by machines. In the second, S2, aritificial intelligence proves to be incapable of adapting to the extreme events of solar activity affecting satellites and internet communications globally. HRD rebuilds trust in the collective human ability to work together collaboratively to restore a team ethic and rebuild. The scenarios are discussed and a recommendation is made for HRD research to consider the direction and value of their work and how progress in academic life might be reconstituted to allow more attention to be given to key areas of machine learning and artificial intelligence

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene.

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein-ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (TP53, IDH1, FBXW7, SDH-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST

Bridging flavour violation and leptogenesis in SU(3) family models

We reconsider basic, in the sense of minimal field content, Pati-Salam x SU(3) family models which make use of the Type I see-saw mechanism to reproduce the observed mixing and mass spectrum in the neutrino sector. The goal of this is to achieve the observed baryon asymmetry through the thermal decay of the lightest right-handed neutrino and at the same time to be consistent with the expected experimental lepton flavour violation sensitivity. This kind of models have been previously considered but it was not possible to achieve a compatibility among all of the ingredients mentioned above. We describe then how different SU(3) messengers, the heavy fields that decouple and produce the right form of the Yukawa couplings together with the scalars breaking the SU(3) symmetry, can lead to different Yukawa couplings. This in turn implies different consequences for flavour violation couplings and conditions for realizing the right amount of baryon asymmetry through the decay of the lightest right-handed neutrino. Also a highlight of the present work is a new fit of the Yukawa textures traditionally embedded in SU(3) family models.Comment: 26 pages, 5 figures, Some typos correcte

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

Uptake and outcomes of a prevention-of mother-to-child transmission (PMTCT) program in Zomba district, Malawi

<p>Abstract</p> <p>Background</p> <p>HIV prevalence among pregnant women in Malawi is 12.6%, and mother-to-child transmission is a major route of transmission. As PMTCT services have expanded in Malawi in recent years, we sought to determine uptake of services, HIV-relevant infant feeding practices and mother-child health outcomes.</p> <p>Methods</p> <p>A matched-cohort study of HIV-infected and HIV-uninfected mothers and their infants at 18-20 months post-partum in Zomba District, Malawi. 360 HIV-infected and 360 HIV-uninfected mothers were identified through registers. 387 mother-child pairs were included in the study.</p> <p>Results</p> <p>10% of HIV-infected mothers were on HAART before delivery, 27% by 18-20 months post-partum. sd-NVP was taken by 75% of HIV-infected mothers not on HAART, and given to 66% of infants. 18% of HIV-infected mothers followed all current recommended PMTCT options. HIV-infected mothers breastfed fewer months than HIV-uninfected mothers (12 vs.18, respectively; <it>p </it>< 0.01). 19% of exposed versus 5% of unexposed children had died by 18-20 months; <it>p </it>< 0.01. 28% of exposed children had been tested for HIV prior to the study, 76% were tested as part of the study and 11% were found HIV-positive. HIV-free survival by 18-20 months was 66% (95%CI 58-74). There were 11(6%) maternal deaths among HIV-infected mothers only.</p> <p>Conclusion</p> <p>This study shows low PMTCT program efficiency and effectiveness under routine program conditions in Malawi. HIV-free infant survival may have been influenced by key factors, including underuse of HAART, underuse of sd-NVP, and suboptimal infant feeding practices. Maternal mortality among HIV-infected women demands attention; improved maternal survival is a means to improve infant survival.</p

Publisher Correction:Voices of biotech leaders (Nature Biotechnology, (2021), 39, 6, (654-660), 10.1038/s41587-021-00941-4)

In the version of this article initially published, an author name was given as Abasi Ene Abong. The correct name is Abasi Ene-Obong. Also, the affiliation for Sebastian Giwa was given as Elevian, Pagliuca Harvard Life Lab, Allston, MA, USA. The correct affiliations are Biostasis Research Institute, Berkeley, CA, USA; Sylvatica Biotech, North Charleston, SC, USA; and Humanity Bio, Kensington, CA, USA. An affiliation for Jeantine Lunshof was given as Department of Genetics, Harvard Medical School, Boston, MA, USA. The correct affiliation is Wyss Institute for Biological Engineering, Harvard University, Boston, MA, USA. The errors have been corrected in the PDF and HTML versions of the article

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Foot-and-Mouth Disease Virus Persists in the Light Zone of Germinal Centres

Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV “carrier state” and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. Here we show by laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborate by in situ hybridization that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study