UN Forum series – “outside-in” and “inside-out” human rights measurement tools: how numbers can become the lingua franca of business and human rights

This post was contributed by Michael A. Santoro, Professor of Management and Global Business at Rutgers Business School and Co-Editor of Business and Human Rights Journal. In July 2015, the Secretary-General of the United Nations transmitted a report to the General Assembly prepared by the Working Group on human rights and transnational corporations and other business enterprises. The Working Group’s report comprehensively lays out the importance of measurement to the implementation of the UN Guiding Principles on Business and Human Rights

Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib.

BackgroundTransforming growth factor beta (TGF-β) signalling is involved in the development of hepatocellular carcinoma (HCC). We followed changes in biomarkers during treatment of patients with HCC with the TGF-βRI/ALK5 inhibitor galunisertib.MethodsThis phase 2 study (NCT01246986) enrolled second-line patients with advanced HCC into one of two cohorts of baseline serum alpha-fetoprotein (AFP): Part A (AFP ≥1.5x ULN) or Part B (AFP <1.5x ULN). Baseline and postbaseline levels of AFP, TGF-β1, E-cadherin, selected miRNAs, and other plasma proteins were monitored.ResultsThe study enrolled 149 patients (Part A, 109; Part B, 40). Median OS was 7.3 months in Part A and 16.8 months in Part B. Baseline AFP, TGF-β1, E-cadherin, and an additional 16 plasma proteins (such as M-CSF, IL-6, ErbB3, ANG-2, neuropilin-1, MIP-3 alpha, KIM-1, uPA, IL-8, TIMP-1, ICAM-1, Apo A-1, CA-125, osteopontin, tetranectin, and IGFBP-1) were found to correlate with OS. In addition, a range of miRs were found to be associated with OS. In AFP responders (21% of patients in Part A with decrease of >20% from baseline) versus non-responders, median OS was 21.5 months versus 6.8 months (p = 0.0015). In TGF-β1 responders (51% of all patients) versus non-responders, median OS was 11.2 months versus 5.3 months (p = 0.0036).ConclusionsConsistent with previous findings, both baseline levels and changes from baseline of circulating AFP and TGF-β1 function as prognostic indicators of survival. Future trials are needed to confirm and extend these results

Crystal structure of solid Oxygen at high pressure and low temperature

Results of X-ray diffraction experiments on solid oxygen at low temperature and at pressures up to 10 GPa are presented.A careful sample preparation and annealing around 240 K allowed to obtain very good diffraction patterns in the orthorhombic delta-phase. This phase is stable at low temperature, in contrast to some recent data [Y. Akahama et al., Phys. Rev. B64, 054105 (2001)], and transforms with decreasing pressure into a monoclinic phase, which is identified as the low pressure alpha-phase. The discontinuous change of the lattice parameters, and the observed metastability of the alpha-phase increasing pressure suggest that the transition is of the first order.Comment: 4 pages with three figure

Following the banking cycle of umbilical cord blood in India: the disparity between prebanking persuasion and post-banking utilization

To address critique of the rare uptake of umbilical cord blood (UCB) in private banks, hybrid-banking models would combine the advantages of ‘public UCB banking’ and private UCB banking by responding to both market forces and public needs. We question both by following the cycle of UCB banking in India: the circulation and stagnation of UCB as waste, gift, biological insurance, enclaved good, source of saving lives, and commodity through various practices of public, private and hybrid UCB banking. Making the journey from ‘recruitment’, ‘collection’ and ‘banking’ to ‘research’ and ‘therapy’ allowed us to identify concerns about the transparency of this cycle. Drawing on archival research and fieldwork interviews with different stakeholders in UCB banks in India, this article shows how private/hybrid cord blood banks are competing for their market share and its implication for the circulation of UCB: speculation, stagnation and opacity

PRAMEL7/CUL2 axis regulates NuRD stability to establish ground-state pluripotency in embryonic stem cells

Pluripotency is established in E4.5 preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of pluripotency, however, they only partially resemble the gene expression signature of developmental ground-state. Induced PRAMEL7 expression, a protein highly expressed in the ICM but lowly expressed in ESCs, reprograms developmentally advanced ESC+serum into ground-state pluripotency by causing DNA hypomethylation and gene expression signature close to developmental ground-state. However, how PRAMEL7 reprograms gene expression remains elusive. Here we show that PRAMEL7 associates with Cullin2 (CUL2) and this interaction is required to establish ground-state gene expression. PRAMEL7 recruits CUL2 to chromatin and targets for proteasomal degradation regulators of repressive chromatin, including NuRD complex. PRAMEL7 antagonizes NuRD-mediated repression of genes implicated in pluripotency by decreasing NuRD stability and promoter association in a CUL2-dependent manner. Our data link proteasome degradation pathways to ground-state gene expression, offering insights to generate in vitro models to reproduce the in vivo ground-state pluripotency

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

Detection of mostly viral pathogens and high proportion of antibiotic treatment initiation in hospitalised children with community-acquired pneumonia in Switzerland – baseline findings from the first two years of the KIDS-STEP trial

AIMS OF THE STUDY: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland. METHODS: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens. RESULTS: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation <92% was found in 43 (31.2%). Forty-three participants (29.0%) were already on antibiotic treatment prior to admission and 104 participants (75.4%) received antibiotic treatment on admission. Pathogen testing results were available from 132 children: 31 (23.5%) had respiratory syncytial virus detected, 21 (15.9%) human metapneumovirus. The pathogens detected showed expected seasonal and age preponderance and were not associated with chest X-ray findings. CONCLUSIONS: In the context of the predominantly viral pathogens detected, the majority of antibiotic treatment is probably unnecessary. The ongoing trial, as well as other studies, will be able to provide comparative pathogen detection data to compare pre- and post-COVID-19-pandemic settings

Knowledge Tracing with Sequential Key-Value Memory Networks

Can machines trace human knowledge like humans? Knowledge tracing (KT) is a fundamental task in a wide range of applications in education, such as massive open online courses (MOOCs), intelligent tutoring systems, educational games, and learning management systems. It models dynamics in a student's knowledge states in relation to different learning concepts through their interactions with learning activities. Recently, several attempts have been made to use deep learning models for tackling the KT problem. Although these deep learning models have shown promising results, they have limitations: either lack the ability to go deeper to trace how specific concepts in a knowledge state are mastered by a student, or fail to capture long-term dependencies in an exercise sequence. In this paper, we address these limitations by proposing a novel deep learning model for knowledge tracing, namely Sequential Key-Value Memory Networks (SKVMN). This model unifies the strengths of recurrent modelling capacity and memory capacity of the existing deep learning KT models for modelling student learning. We have extensively evaluated our proposed model on five benchmark datasets. The experimental results show that (1) SKVMN outperforms the state-of-the-art KT models on all datasets, (2) SKVMN can better discover the correlation between latent concepts and questions, and (3) SKVMN can trace the knowledge state of students dynamics, and a leverage sequential dependencies in an exercise sequence for improved predication accuracy

On the population of primordial star clusters in the presence of UV background radiation

We use the algorithm of Cole et al. to generate merger trees for the first star clusters in a Λ cold dark matter (ΛCDM) cosmology under an isotropic ultraviolet background radiation field, parametrized by J21. We have investigated the problem in two ways: a global radiation background and local radiative feedback surrounding the first star clusters. Cooling in the first haloes at high redshift is dominated by molecular hydrogen, H2– we call these Generation 1 objects. At lower redshift and higher virial temperature, Tvir≳ 104 K, electron cooling dominates – we call these Generation 2. Radiation fields act to photodissociate H2, but also generate free electrons that can help to catalyze its production. At modest radiation levels, J21/(1 +z)3∼ 10−12–10−7, the nett effect is to enhance the formation of Generation 1 star clusters. At higher fluxes, the heating from photoionization dominates and halts their production. With a realistic build‐up of flux over time, the period of enhanced H2 cooling is so fleeting as to be barely discernable and the nett effect is to move primordial star cluster formation towards Generation 2 objects at lower redshift. A similar effect is seen with local feedback. Provided that enough photons are produced to maintain ionization of their host halo, they will suppress the cooling in Generation 1 haloes and boost the numbers of primordial star clusters in Generation 2 haloes. Significant suppression of Generation 1 haloes occurs for specific photon fluxes in excess of about 1043 ph s−1 M−1⊙

Measurement of the t(t)over-bar production cross section in the dilepton channel in pp collisions at √s=8 TeV

The top-antitop quark (t (t) over bar) production cross section is measured in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC, using a data sample corresponding to an integrated luminosity of 5.3 fb(-1). The measurement is performed by analysing events with a pair of electrons or muons, or one electron and one muon, and at least two jets, one of which is identified as originating from hadronisation of a bottom quark. The measured cross section is 239 +/- 2 (stat.) +/- 11 (syst.) +/- 6 (lum.) pb, for an assumed top-quark mass of 172.5 GeV, in agreement with the prediction of the standard model