Hydroxyl as a Tracer of H2 in the Envelope of MBM40

We observed 51 positions in the OH 1667 MHz main line transitions in the translucent, high latitude cloud MBM40. We detected OH emission in 8 out of 8 positions in the molecular core of the cloud and 24 out of 43 in the surrounding, lower extinction envelope and periphery of the cloud. Using a linear relationship between the integrated OH line intensity and E(B-V), we estimate the mass in the core, the envelope, and the periphery of the cloud to be 4, 8, and 5 solar masses. As much as a third of the total cloud mass may be found in the in the periphery (E(B-V) $<$ 0.12 mag) and about a half in the envelope (0.12 $\le$ E(B-V) $\le$ 0.17 mag). If these results are applicable to other translucent clouds the OH 1667 MHz line is an excellent tracer of gas in very low extinction regions and high-sensitivity mapping of the envelopes of molecular clouds may reveal the presence of significant quantities of molecular mass.Comment: 26 pages, 3 figures, and 5 table

Universal reduction of pressure between charged surfaces by long-wavelength surface charge modulation

We predict theoretically that long-wavelength surface charge modulations universally reduce the pressure between the charged surfaces with counterions compared with the case of uniformly charged surfaces with the same average surface charge density. The physical origin of this effect is the fact that surface charge modulations always lead to enhanced counterion localization near the surfaces, and hence, fewer charges at the midplane. We confirm the last prediction with Monte Carlo simulations.Comment: 8 pages 1 figure, Europhys. Lett., in pres

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

Counterion Condensation and Fluctuation-Induced Attraction

We consider an overall neutral system consisting of two similarly charged plates and their oppositely charged counterions and analyze the electrostatic interaction between the two surfaces beyond the mean-field Poisson-Boltzmann approximation. Our physical picture is based on the fluctuation-driven counterion condensation model, in which a fraction of the counterions is allowed to ``condense'' onto the charged plates. In addition, an expression for the pressure is derived, which includes fluctuation contributions of the whole system. We find that for sufficiently high surface charges, the distance at which the attraction, arising from charge fluctuations, starts to dominate can be large compared to the Gouy-Chapmann length. We also demonstrate that depending on the valency, the system may exhibit a novel first-order binding transition at short distances.Comment: 15 pages, 8 figures, to appear in PR

Clinical features of patients with homozygous complement C4A or C4B deficiency

Introduction Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Material and methods Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Results Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%Cl = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%Cl = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%Cl = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%Cl = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%Cl = 1.22-4.88, p = 0.010). Conclusion This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.Peer reviewe

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort

ObjectiveLong-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab.MethodsThe study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records.ResultsThe study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with >= 1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P ConclusionsUstekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.</div

An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

Background: Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up.Results: We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus.Conclusions: This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations