A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals

Given q as the global frequency of the alleles causing a disease, any allele with a frequency higher than q minus the cumulative frequency of the previously known disease-causing mutations (threshold) cannot be the cause of that disease. This principle was applied to the analysis of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in order to decide whether they are the cause of cystic fibrosis. A total of 191 DNA samples fl-om random individuals from Italy, France, and Spain were investigated by DGGE (denaturing gradient gel electrophoresis) analysis of all the coding and proximal non-coding regions of the gene. The mutations detected by DGGE were identified by sequencing. The sample size was sufficient to select essentially all mutations with a frequency of at least 0.01. A total of 46 mutations was detected, 20 of which were missense mutations. Four new mutations were identified: 1341+28 C/T, 2082 C/T, L1096R, and I1131V. Thirteen mutations (125 G/C, 875+40 A/G, TTGAn, IVS8-6 5T, IVS8-6 9T, 1525-61 A/G, M470V, 2693 T/G, 3061-65 C/A, 4002 A/G, 4521 G/A, IVS8 TG10, IVS8 TG12) were classified as non-CF-causing alleles on the basis of their frequency. The remaining mutations have a cumulative frequency far exceeding q; therefore, most of them cannot be CF-causing mutations. This is the first random survey capable of detecting all the polymorphisms of the coding sequence of a gene

The hepatitis D virus in Italy. A vanishing infection, not yet a vanished disease

Introduction: Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. Objectives: To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. Methods: From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. Results: At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2–17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000–2009 to 50.2% (130/259) in 2010–2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. Conclusion: Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation

Study of 16 Portuguese activated sludge systems based on filamentous bacteria populations and their relationships with environmental parameters

A survey in 16 activated sludge waste water treatment plants (WWTP) was conducted to contribute to the knowledge of the environmental parameters that determine the composition of the filamentous community. A total of 128 samples of mixed liquor from municipal WWTP were collected during 2 years, and 22 filamentous morphotypes were identified. The most frequent and abundant filamentous bacteria were, in both cases and by this order, type 0041/0675, type 0092, Microthrix parvicella and 1851, nocardioforms and Haliscomenobacter hydrossis. Concerning dominance, type 1851 was the most frequently dominant morphotype, followed by M. parvicella and types 0092 and 0041/0675. These were also, and by this order, the dominant morphotypes during bulking occurrences. Significant correlations were obtained between the abundance of filamentous bacteria and environmental parameters, but multivariate statistical analysis only confirmed the correlation between type 0092 and Sludge Volume Index (SVI), emphasizing the association of this filament with bulking. The discussion of the results in light of published works was complicated by the random use of terms such as frequency, abundance, and dominance with different and often unclear meanings. This reinforces the need of clarifying these terms when discussing the causes of filamentous overgrowth in WWTP.Portuguese Foundation for Science and Technology (FCT) and the European Community fund FEDER, through Program COMPETE, in the ambit of the Projects FCOMP-01-0124-FEDER-007025 (PTDC/AMB/68393/2006), PEst-OE/EQB/LA0023/2013, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), and the Project BBioEnv - Biotechnology and Bioengineering for a sustainable world,REF. NORTE-07-0124- FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. PhD grant SFRH/BD/64848/200

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection

Background: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking.Methods: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out.Results: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score >= 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE >= 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score >= 11 and SOFA score >= 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective.Conclusions: Both INCREMENT-SOT-CPE >= 11 and SOFA >= 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT

A Measurement of the CMB Temperature Power Spectrum and Constraints on Cosmology from the SPT-3G 2018 TT/TE/EE Data Set

We present a sample-variance-limited measurement of the temperature power spectrum ($TT$) of the cosmic microwave background (CMB) using observations of a $\sim\! 1500 \,\mathrm{deg}^2$ field made by SPT-3G in 2018. We report multifrequency power spectrum measurements at 95, 150, and 220GHz covering the angular multipole range $750 \leq \ell < 3000$. We combine this $TT$ measurement with the published polarization power spectrum measurements from the 2018 observing season and update their associated covariance matrix to complete the SPT-3G 2018 $TT/TE/EE$ data set. This is the first analysis to present cosmological constraints from SPT $TT$, $TE$, and $EE$ power spectrum measurements jointly. We blind the cosmological results and subject the data set to a series of consistency tests at the power spectrum and parameter level. We find excellent agreement between frequencies and spectrum types and our results are robust to the modeling of astrophysical foregrounds. We report results for $\Lambda$CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra $A_\mathrm{L}$, the effective number of neutrino species $N_{\mathrm{eff}}$, the primordial helium abundance $Y_{\mathrm{P}}$, and the baryon clumping factor due to primordial magnetic fields $b$. We find that the SPT-3G 2018 $T/TE/EE$ data are well fit by $\Lambda$CDM with a probability-to-exceed of $15\%$. For $\Lambda$CDM, we constrain the expansion rate today to $H_0 = 68.3 \pm 1.5\,\mathrm{km\,s^{-1}\,Mpc^{-1}}$ and the combined structure growth parameter to $S_8 = 0.797 \pm 0.042$. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either data set are within $<1\,\sigma$ of each other. (abridged)Comment: 35 Pages, 17 Figures, 11 Table

Flaring Stars in a Non-targeted mm-wave Survey with SPT-3G

We present a flare star catalog from four years of non-targeted millimeter-wave survey data from the South Pole Telescope (SPT). The data were taken with the SPT-3G camera and cover a 1500-square-degree region of the sky from $20^{h}40^{m}0^{s}$ to $3^{h}20^{m}0^{s}$ in right ascension and $-42^{\circ}$ to $-70^{\circ}$ in declination. This region was observed on a nearly daily cadence from 2019-2022 and chosen to avoid the plane of the galaxy. A short-duration transient search of this survey yields 111 flaring events from 66 stars, increasing the number of both flaring events and detected flare stars by an order of magnitude from the previous SPT-3G data release. We provide cross-matching to Gaia DR3, as well as matches to X-ray point sources found in the second ROSAT all-sky survey. We have detected flaring stars across the main sequence, from early-type A stars to M dwarfs, as well as a large population of evolved stars. These stars are mostly nearby, spanning 10 to 1000 parsecs in distance. Most of the flare spectral indices are constant or gently rising as a function of frequency at 95/150/220 GHz. The timescale of these events can range from minutes to hours, and the peak $\nu L_{\nu}$ luminosities range from $10^{27}$ to $10^{31}$ erg s$^{-1}$ in the SPT-3G frequency bands

The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients

Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance

The Design and Integrated Performance of SPT-3G

SPT-3G is the third survey receiver operating on the South Pole Telescope dedicated to high-resolution observations of the cosmic microwave background (CMB). Sensitive measurements of the temperature and polarization anisotropies of the CMB provide a powerful dataset for constraining cosmology. Additionally, CMB surveys with arcminute-scale resolution are capable of detecting galaxy clusters, millimeter-wave bright galaxies, and a variety of transient phenomena. The SPT-3G instrument provides a significant improvement in mapping speed over its predecessors, SPT-SZ and SPTpol. The broadband optics design of the instrument achieves a 430 mm diameter image plane across observing bands of 95 GHz, 150 GHz, and 220 GHz, with 1.2 arcmin FWHM beam response at 150 GHz. In the receiver, this image plane is populated with 2690 dual-polarization, tri-chroic pixels (~16000 detectors) read out using a 68X digital frequency-domain multiplexing readout system. In 2018, SPT-3G began a multiyear survey of 1500 deg$^{2}$ of the southern sky. We summarize the unique optical, cryogenic, detector, and readout technologies employed in SPT-3G, and we report on the integrated performance of the instrument.Comment: 25 pages, 11 figures. Submitted to ApJ