Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis

To assess the potential use of hyaluronic acid (HA) as adjuvant therapy in rheumatoid arthritis, the anti-inflammatory and chondroprotective effects of HA were analysed in experimental rat antigen-induced arthritis (AIA). Lewis rats with AIA were subjected to short-term (days 1 and 8, n = 10) or long-term (days 1, 8, 15 and 22, n = 10) intra-articular treatment with microbially manufactured, high-molecular-weight HA (molecular weight, 1.7 × 10(6 )Da; 0.5 mg/dose). In both tests, 10 buffer-treated AIA rats served as arthritic controls and six healthy animals served as normal controls. Arthritis was monitored by weekly assessment of joint swelling and histological evaluation in the short-term test (day 8) and in the long-term test (day 29). Safranin O staining was employed to detect proteoglycan loss from the epiphyseal growth plate and the articular cartilage of the arthritic knee joint. Serum levels of IL-6, tumour necrosis factor alpha and glycosaminoglycans were measured by ELISA/kit systems (days 8 and 29). HA treatment did not significantly influence AIA in the short-term test (days 1 and 8) but did suppress early chronic AIA (day 15, P < 0.05); however, HA treatment tended to aggravate chronic AIA in the long-term test (day 29). HA completely prevented proteoglycan loss from the epiphyseal growth plate and articular cartilage on day 8, but induced proteoglycan loss from the epiphyseal growth plate on day 29. Similarly, HA inhibited the histological signs of acute inflammation and cartilage damage in the short-term test, but augmented acute and chronic inflammation as well as cartilage damage in the long-term test. Serum levels of IL-6, tumour necrosis factor alpha, and glycosaminoglycans were not influenced by HA. Local therapeutic effects of HA in AIA are clearly biphasic, with inhibition of inflammation and cartilage damage in the early chronic phase but with promotion of joint swelling, inflammation and cartilage damage in the late chronic phase

Beam test performance of a prototype module with Short Strip ASICs for the CMS HL-LHC tracker upgrade

The Short Strip ASIC (SSA) is one of the four front-end chips designed for the upgrade of the CMS Outer Tracker for the High Luminosity LHC. Together with the Macro-Pixel ASIC (MPA) it will instrument modules containing a strip and a macro-pixel sensor stacked on top of each other. The SSA provides both full readout of the strip hit information when triggered, and, together with the MPA, correlated clusters called stubs from the two sensors for use by the CMS Level-1 (L1) trigger system. Results from the first prototype module consisting of a sensor and two SSA chips are presented. The prototype module has been characterized at the Fermilab Test Beam Facility using a 120 GeV proton beam.Peer reviewe

HIV/AIDS, declining family resources and the community safety net

Families play central roles in the HIV/AIDS pandemic, caring for both orphaned children and the ill. This extra caregiving depletes two family resources essential for supporting children: time and money. We use recent data from published studies in sub-Saharan Africa to illustrate deficits and document community responses. In Botswana, parents caring for the chronically ill had less time for their preschool children (74 versus 96 hours per month) and were almost twice as likely to leave children home alone (53% versus 27%); these children experienced greater health and academic problems. Caregiving often prevented adults from working full time or earning their previous level of income; 47% of orphan caregivers and 64% of HIV/AIDS caregivers reported financial difficulties due to caregiving. Communities can play an important role in helping families provide adequate childcare and financial support. Unfortunately, while communities commonly offer informal assistance, the value of such support is not adequate to match the magnitude of need: 75% of children's families in Malawi received assistance from their social network, but averaging only US$81 annually. We suggest communities can strengthen the capacity of families by implementing affordable quality childcare for 0–6 year olds, after-school programming for older children and youth, supportive care for ill children and parents, microlending to enhance earnings, training to increase access to quality jobs, decent working conditions, social insurance for the informal sector, and income and food transfers when families are unable to make ends meet

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement

Study of dijet events with large rapidity separation in proton-proton collisions at root s=2.76 TeV

The cross sections for inclusive and Mueller-Navelet dijet production are measured as a function of the rapidity separation between the jets in proton-proton collisions at root s = 2.76 TeV for jets with transverse momentum p(T) > 35 GeV and rapidity vertical bar y vertical bar 20 GeV is introduced to improve the sensitivity to the effects of the Balitsky-Fadin-Kuraev-Lipatov (BFKL) evolution. The measurement is compared with the predictions of various Monte Carlo models based on leading-order and next-to-leading-order calculations including the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi leading-logarithm (LL) parton shower as well as the LL BFKL resummation.Peer reviewe

Search for electroweak production of charginos and neutralinos in proton-proton collisions at root s=13 TeV

A direct search for electroweak production of charginos and neutralinos is presented. Events with three or four leptons, with up to two hadronically decaying tau leptons, or two same-sign light leptons are analyzed. The data sample consists of 137 fb(-1) of proton-proton collisions with a center of mass energy of 13 TeV, recorded with the CMS detector at the LHC. The results are interpreted in terms of several simplified models. These represent a broad range of production and decay scenarios for charginos and neutralinos. A parametric neural network is used to target several of the models with large backgrounds. In addition, results using orthogonal search regions are provided for all the models, simplifying alternative theoretical interpretations of the results. Depending on the model hypotheses, charginos and neutralinos with masses up to values between 300 and 1450 GeV are excluded at 95% confidence level.Peer reviewe

Probing Charm Quark Dynamics via Multiparticle Correlations in Pb-Pb Collisions at root s(NN)=5.02 TeV

Multiparticle azimuthal correlations of prompt D-0 mesons arc measured in Pb-Pb collisions at a nucleon-nucleon center-of-mass energy of root s(NN) = 5.02 TeV. For the first time, a four-particle cumulant method is used to extract the second Fourier coefficient of the azimuthal distribution (v(2)) of D-0 mesons as a function of event centrality and the D-0 transverse momentum. The ratios of the four-particle v(2) values to previously measured two-particle cumulant results provide direct experimental access to event-by-event fluctuations of charm quark azimuthal anisotropies. These ratios are also found to be comparable to those of inclusive charged particles in the event. However, hints of deviations are seen in the most central and peripheral collisions. To investigate the origin of flow fluctuations in the charm sector, these measurements are compared to a model implementing fluctuations of charm quark energy loss via collisional or radiative processes in the quark-gluon plasma. These models cannot quantitatively describe the data over the full transverse momentum and centrality ranges, although the calculations with collisional energy loss provide a better description of the data.Peer reviewe