2P15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment

Elevated fetal hemoglobin (HbF) ameliorates the clinical severity of hemoglobinopathies such as β-thalassemia and sickle cell anemia. Currently, the only curative approach for individuals under chronic transfusion/chelation support therapy is allogeneic stem cell transplantation. However, recent analyses of heritable variations in HbF levels have provided a new therapeutic target for HbF reactivation: the transcriptional repressor BCL11A. Erythroid-specific BCL11A abrogation is now actively being sought as a therapeutic avenue, but the specific impact of such disruption in humans remains to be determined. Although single nucleotide polymorphisms in BCL11A erythroid regulatory elements have been reported, coding mutations are scarcer. It is thus of great interest that patients have recently been described with microdeletions encompassing BCL11A. These patients display neurodevelopmental abnormalities, but whether they show increased HbF has not been reported. We have examined the hematological phenotype, HbF levels, and erythroid BCL11A expression in 3 such patients. Haploinsufficiency of BCL11A induces only partial developmental g-globin silencing. Of greater interest is that a patient with a downstream deletion exhibits reduced BCL11A expression and increased HbF. Novel erythroid-specific regulatory elements in this region may be required for normal erythroid BCL11A expression, whereas loss of separate elements in the developing brain may explain the neurological phenotype

Annual Reports of the Selectmen, Assessors, Overseers of Poor, Treasurer, and Supervisor of Schools, of the Town of Winthrop, for the Year Ending March 14, 1881

Natural materials, such as collagen, can assemble with multiple levels of organization in solution. Achieving a similar degree of control over morphology, stability and hierarchical organization with equilibrium synthetic materials remains elusive. For the assembly of peptidic materials the process is controlled by a complex interplay between hydrophobic interactions, electrostatics and secondary structure formation. Consequently, fine tuning the thermodynamics and kinetics of assembly remains extremely challenging. Here, we synthesized a set of block co polypeptides with varying hydrophobicity and ability to form secondary structure. From this set we select a sequence with balanced interactions that results in the formation of high-aspect ratio thermodynamically favored nanotubes, stable between pH 2 and 12 and up to 80 °C. This stability permits their hierarchical assembly into bundled nanotube fibers by directing the pH and inducing complementary zwitterionic charge behavior. This block co-polypeptide design strategy, using defined sequences, provides a straightforward approach to creating complex hierarchical peptide-based assemblies with tunable interactions

Use of electronic devices by people attending vision rehabilitation services in Italy: A study based on the device and aids registry (D.A.Re)

Purpose To investigate the characteristics of electronic device users, specifically smartphones and tablets, in the Device & Aids Register (D.A.Re), from several low-vision rehabilitation services in Italy. Methods We collected general and clinical information about ocular and systemic diseases, visual function, reading speed and Instrumental Activities of Daily Living (IADL) questionnaire score. Technological details of each optical and electronic device, (including screen size, touch-screen and OCR functions, text-to-speech function) were also collected. Results 1218 patients (752 females and 466 males) were included in our analysis, mean age 71.5 (±18.8) years. Users of electronic aids (n.237) were slightly younger (67 vs 72 years, p < 0.001) than non-users (n.981), had a worse reading speed (38 vs 65 words/minute), critical print size (43 vs 28 print size, p < 0.001), poorer visual acuity (VA)(1.0 logMAR or less: 30% non-users vs 73% users, p < 0.001) and more commonly visual field restriction within 10° (23% vs 14%, p = 0.001). A similar proportion of users and non-users were retired (about 70%) and about 16–17% were employed. The use of portable electronic devices (5″or less, p < 0.001; 6″ to 18″ screen size, p = 0.017) was associated with better IADL scores, and the use of stand devices with worse IADL score (p < 0.001); Furthermore, using smartphones and tablets (193 subjects) was strongly associated with better IADL scores. Conclusion We found that using electronic devices, and especially smartphone and tablets, were associated with better vision-related quality of life in low-vision people attending rehabilitation services. While this association does not mean causality, these findings seemed robust to confounder adjustment

Laser spectroscopy for breath analysis : towards clinical implementation

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe

Patients in long-term maintenance therapy for drug use in Italy: analysis of some parameters of social integration and serological status for infectious diseases in a cohort of 1091 patients

BACKGROUND: Heroin addiction often severely disrupts normal social functioning. The aims of this multi-centre study of heroin users in long-term replacement treatment were: i) to provide information on aspects of social condition such as employment, educational background, living status, partner status and any history of drug addiction for partners, comparing these data with that of the general population; ii) to assess the prevalence of hepatitis, syphilis and HIV, because serological status could be a reflection of the social conditions of patients undergoing replacement treatment for drug addiction; iii) to analyse possible relationships between social conditions and serological status. METHODS: A cross-sectional study was carried out in sixteen National Health Service Drug Addiction Units in northern Italy. The data were collected from February 1, 2002 to August 31, 2002. Recruitment eligibility was: maintenance treatment with methadone or buprenorphine, treatment for the previous six months, and at least 18 years of age. In the centres involved in the study no specific criteria or regulations were established concerning the duration of replacement therapy. Participants underwent a face-to-face interview. RESULTS: The conditions of 1091 drug treatment patients were evaluated. The mean duration of drug use was 14.5 years. Duration was shorter in females, in subjects with a higher educational background, and in stable relationships. Most (68%) had completed middle school (11–14 years of age). Seventy-nine percent were employed and 16% were unemployed. Fifty percent lived with their parents, 34% with a partner and 14% alone. Males lived more frequently with their parents (55%), and females more frequently with a partner (60%). Sixty-seven percent of male patients with a stable relationship had a partner who had never used heroin. HCV prevalence was 72%, HBV antibodies were detected in 42% of patients, while 30% had been vaccinated; 12.5% of subjects were HIV positive and 1.5% were positive for TPHA. CONCLUSION: A significant percentage of heroin users in treatment for opiate addiction in the cohort study have characteristics which indicate reasonable integration within broader society. We posit that the combination of effective treatment and a setting of economic prosperity may enhance the social integration of patients with a history of heroin use

Detection potential of the KM3NeT detector for high-energy neutrinos from the Fermi bubbles

A recent analysis of the Fermi Large Area Telescope data provided evidence for a high-intensity emission of high-energy gamma rays with a E 2 spectrum from two large areas, spanning 50 above and below the Galactic centre (the ‘‘Fermi bubbles’’). A hadronic mechanism was proposed for this gamma-ray emission making the Fermi bubbles promising source candidates of high-energy neutrino emission. In this work Monte Carlo simulations regarding the detectability of high-energy neutrinos from the Fermi bubbles with the future multi-km3 neutrino telescope KM3NeT in the Mediterranean Sea are presented. Under the hypothesis that the gamma-ray emission is completely due to hadronic processes, the results indicate that neutrinos from the bubbles could be discovered in about one year of operation, for a neutrino spectrum with a cutoff at 100 TeV and a detector with about 6 km3 of instrumented volume. The effect of a possible lower cutoff is also considered.Published7–141.8. Osservazioni di geofisica ambientaleJCR Journalrestricte

Expansion cone for the 3-inch PMTs of the KM3NeT optical modules

[EN] Detection of high-energy neutrinos from distant astrophysical sources will open a new window on the Universe. The detection principle exploits the measurement of Cherenkov light emitted by charged particles resulting from neutrino interactions in the matter containing the telescope. A novel multi-PMT digital optical module (DOM) was developed to contain 31 3-inch photomultiplier tubes (PMTs). In order to maximize the detector sensitivity, each PMT will be surrounded by an expansion cone which collects photons that would otherwise miss the photocathode. Results for various angles of incidence with respect to the PMT surface indicate an increase in collection efficiency by 30% on average for angles up to 45 degrees with respect to the perpendicular. Ray-tracing calculations could reproduce the measurements, allowing to estimate an increase in the overall photocathode sensitivity, integrated over all angles of incidence, by 27% (for a single PMT). Prototype DOMs, being built by the KM3NeT consortium, will be equipped with these expansion cones.This work is supported through the EU, FP6 Contract no. 011937, FP7 grant agreement no. 212252, and the Dutch Ministry of Education, Culture and Science.Adrián Martínez, S.; Ageron, M.; Aguilar, JA.; Aharonian, F.; Aiello, S.; Albert, A.; Alexandri, M.... (2013). Expansion cone for the 3-inch PMTs of the KM3NeT optical modules. Journal of Instrumentation. 8(3):1-19. https://doi.org/10.1088/1748-0221/8/03/T03006S1198

Laser spectroscopy on volatile sulfur compounds: possibilities for breath analysis.

There is an emerging interest in the detection of volatile sulfur compounds (VSCs) in the breath environment, given their biological relevance as potential signatures of several pathological conditions. Particularly, laser-based spectroscopic sensors are candidates for conducting accurate breath diagnostics in clinical settings. With these aims in mind, the current status of VSC sensing via laser absorption spectroscopy is reviewed in this paper. Attention has been focused on the most promising exhaled markers of pathological conditions, namely hydrogen sulfide, carbonyl sulfide, methanethiol, carbon disulfide and dimethyl sulfide. Details of the most relevant spectroscopic studies conducted on such molecules are presented, together with suggestions on the future direction of this challenging analytical field

Laser spectroscopy on volatile sulfur compounds: possibilities for breath analysis.

There is an emerging interest in the detection of volatile sulfur compounds (VSCs) in the breath environment, given their biological relevance as potential signatures of several pathological conditions. Particularly, laser-based spectroscopic sensors are candidates for conducting accurate breath diagnostics in clinical settings. With these aims in mind, the current status of VSC sensing via laser absorption spectroscopy is reviewed in this paper. Attention has been focused on the most promising exhaled markers of pathological conditions, namely hydrogen sulfide, carbonyl sulfide, methanethiol, carbon disulfide and dimethyl sulfide. Details of the most relevant spectroscopic studies conducted on such molecules are presented, together with suggestions on the future direction of this challenging analytical field