New stratigraphic and structural evidence for Late Pleistocene surface faulting along the Monte Olimpino Backthrust (Lombardia, N Italy)

We summarize some preliminary results achieved during the investigations conducted for the CARG Project, geological sheet n. 75 “Como”, i.e. the analysis of the Quaternary evolution of the “Monte Olimpino Backthrust” and the evaluation of its seismogenic activity. Cross-border field mapping between Ticino (CH) and Lombardia (IT) resulted in the finding of new outcrops (Borgo Vico site, in the north-western sector of the urban area of Como) located along the front of the Monte Olimpino Backthrust, that allowed to recognize evidence for Late Pleistocene reverse surface faulting along this structure. At Borgo Vico, a clastic Tertiary unit, the Villa Olmo Conglomerate, intercalated in the Chiasso Fm. of Early Oligocene age, is thrust over a Late Pleistocene fluvioglacial and glacio-lacustrine sequence (Comerci et alii, 2007). Until now, the Monte Olimpino Backthrust was supposed by most authors to have been active until Tortonian times. Sileo et alii (2007) inferred a Pliocene activity and proposed, based on geomorphic evidence, that fault displacement was still taking place during Pleistocene. However, this is the first time that Pleistocene activity along the Monte Olimpino Backthrust has been documented by unequivocal tectonic offset of late Pleistocene deposits. Paleoseismological analyses are in progress in order to distinguish potential coseismic movement from fault creep during the observed recent displacement

Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute

In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HA. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca2+ ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 hours at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HA, particularly the hydrogel Alg/HA.The authors would like to acknowledge the financial support from FCT (Fundacao para a Ciencia e a Tecnologia) through the grant SFRH/BD/76237/2011 and project ENMED/0002/2010, from FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade-under the project PEst-C/EME/UI0285/2011, as well as to the project I&DT BIOMAT&CELL n. 1372

Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study

Background: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi. Methods: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month. Findings: From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8–7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4–10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre. Interpretation: We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance. Funding: Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK)

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Synsedimentary deformation of Pleistocene glaciolacustrine deposits in the Albese con Cassano Area (Southern Alps, Northern Italy), and possible implications for paleoseismicity.

We describe and interpret the well exposed soft-sediment deformations preserved in a Mid-Pleistocene proglacial sequence outcropping at Albese con Cassano, near Como (Southern Alps, N Italy). The observed deformations affect six distinct stratigraphic intervals within the same depositional sequence. The stratigraphy of this sequence, the geomorphic setting, and the careful geological mapping of the area clearly show that these deformations are not the result of glaciotectonics or cryoturbation, but are due to six separate events of synsedimentary liquefaction. In particular, the 3 basal deformed units include sand and gravel volcanoes that formed at the bottom of a proglacial lake. We examined several hypothesis of possible causative mechanism for the formation of these features. Taking into account all the information available on the local geology and sedimentary environment, it is possible to assess that the liquefaction features at Albese con Cassano had a coseismic origin. To our knowledge, this would be the first report of similar evidence of paleoseismicity in the Lombardia Southern Alps. Also, there is no record of historical liquefaction triggered by seismic events in an area of ca. 70 km of radius near Albese con Cassano, including the town of Como, the large metropolitan area of Milano and most of W Lombardia, that is one of the largest industrial districts in Europe. Therefore, the interpretation of the observed deformations can have critical impact for understanding the current seismicity level in the region, and mitigating the associated risk. In this paper we show that this interpretation is not a simple process. Liquefaction features must be treated with caution in order to derive suitable information for seismic hazard characterization, even if their coseismic origin has been definitely proved. It is necessary to understand the amount of seismic shaking (for instance, in terms of local macroseismic intensity) that can have produced that specific feature at that specific site, the location of the causative seismic event (epicenter and focal depth), and eventually its size (in terms of epicentral intensity and/or earthquake magnitude). In the case of Albese con Cassano, the implications in terms of seismic hazard of the observed possible earthquake paleoliquefactions can only be assessed through the definition of several scenarios, taking into account: a) different thresholds of shaking for triggering the described synsedimentary structures, and b) different seismotectonic frameworks related to the Mid- Pleistocene to Holocene evolution of the S Alps, including seismicity induced by isostatic glacial rebound. We conclude that it is worth checking these scenarios in the field with further paleoseismological research on other possible evidence of past earthquakes