Limiting two-Higgs-doublet models

We update the constraints on two-Higgs-doublet models (2HDMs) focusing on the parameter space relevant to explain the present muon $g$$-$$2$ anomaly, $\Delta a_{\mu}$, in four different types of models, type I, II, "lepton specific" (or X) and "flipped" (or Y). We show that the strong constraints provided by the electroweak precision data on the mass of the pseudoscalar Higgs, whose contribution may account for $\Delta a_{\mu}$, are evaded in regions where the charged scalar is degenerate with the heavy neutral one and the mixing angles $\alpha$ and $\beta$ satisfy the Standard Model limit $\beta-\alpha \approx \pi /2$. We combine theoretical constraints from vacuum stability and perturbativity with direct and indirect bounds arising from collider and $B$~physics. Possible future constraints from the electron $g$$-$$2$ are also considered. If the 126 GeV resonance discovered at the LHC is interpreted as the light CP-even Higgs boson of the 2HDM, we find that only models of type X can satisfy all the considered theoretical and experimental constraints.Comment: 18 pages, 3 figure

A novel software platform for volumetric assessment of ablation completeness

Purpose: To retrospectively evaluate the accuracy of a novel software platform for assessing completeness of percutaneous thermal ablations. Materials & methods: Ninety hepatocellular carcinomas (HCCs) in 50 patients receiving percutaneous ultrasound-guided microwave ablation (MWA) that resulted in apparent technical success at 24-h post-ablation computed tomography (CT) and with ≥1-year imaging follow-up were randomly selected from a 320 HCC ablation database (2010–2016). Using a novel volumetric registration software, pre-ablation CT volumes of the HCCs without and with the addition of a 5 mm safety margin, and corresponding post-ablation necrosis volumes were segmented, co-registered and overlapped. These were compared to visual side-by-side inspection of axial images. Results: At 1-year follow-up, CT showed absence of local tumor progression (LTP) in 69/90 (76.7%) cases and LTP in 21/90 (23.3%). For HCCs classified by the software as "incomplete tumor treatments", LTP developed in 13/17 (76.5%) and all 13 (100%) of these LTPs occurred exactly where residual non-ablated tumor was identified by retrospective software analysis. HCCs classified as "complete ablation with <100% 5 mm ablative margins" had LTP in 8/49 (16.3%), while none of 24 HCCs with "complete ablation including 100% 5 mm ablative margins" had LTP. Differences in LTP between both partially ablated HCCs vs completely ablated HCCs, and ablated HCCs with <100% vs with 100% 5 mm margins were statistically significant (p < .0001 and p = .036, respectively). Thus, 13/21 (61.9%) incomplete tumor treatments could have been detected immediately, were the software available at the time of ablation. Conclusions: A novel software platform for volumetric assessment of ablation completeness may increase the detection of incompletely ablated tumors, thereby holding the potential to avoid subsequent recurrences

Association of Autoimmunity to Autonomic Nervous Structures With Nerve Function in Patients With Type 1 Diabetes: A 16-Year Prospective Study

OBJECTIVE We prospectively evaluate the association between autoimmunity to autonomic nervous structures and autonomic neuropathy in type 1 diabetes in relation to clinical variables. RESEARCH DESIGN AND METHODS A cohort of 112 patients with type 1 diabetes was prospectively followed from adolescence (T0) to approximately 4 (T4) and 16 (T16) years later. Standard cardiovascular (CV) tests and neurological examination were performed and related to the presence of circulating antibodies (Ab) to autonomic nervous structures detected at T0 and T4. Quality of life was assessed by a diabetes-specific questionnaire. RESULTS Sixty-six patients (59% of the cohort) were re-examined at T16 (age 31.4 ± 2 years; disease duration 23.4 ± 3.7 years). Nineteen had circulating Ab to autonomic structures. Prevalence of abnormal tests and autonomic symptoms were higher in Ab-positive (68 and 26%, respectively) than Ab-negative (32 and 4%) patients ( P 1c increase). Presence of Ab carried over a 68% probability of developing an altered CV test; absence of Ab carried a 91% probability of not having an altered DB test and an 89% probability of not having an altered Valsalva ratio. Autonomic neuropathy was independently associated with worse quality of life. CONCLUSIONS Circulating Ab to autonomic structures are associated with the development of autonomic dysfunction in young diabetic patients independent of glycemic control

Real-Time On-Site Diagnosis of Quarantine Pathogens in Plant Tissues by Nanopore-Based Sequencing

Rapid and sensitive assays for the identification of plant pathogens are necessary for the effective management of crop diseases. The main limitation of current diagnostic testing is the inability to combine broad and sensitive pathogen detection with the identification of key strains, pathovars, and subspecies. Such discrimination is necessary for quarantine pathogens, whose management is strictly dependent on genotype identification. To address these needs, we have established and evaluated a novel all-in-one diagnostic assay based on nanopore sequencing for the detection and simultaneous characterization of quarantine pathogens, using Xylella fastidiosa as a case study. The assay proved to be at least as sensitive as standard diagnostic tests and the quantitative results agreed closely with qPCR-based analysis. The same sequencing results also allowed discrimination between subspecies when present either individually or in combination. Pathogen detection and typing were achieved within 13 min of sequencing owing to the use of an internal control that allowed to stop sequencing when sufficient data had accumulated. These advantages, combined with the use of portable equipment, will facilitate the development of next-generation diagnostic assays for the efficient monitoring of other plant pathogens

Long-Lasting Protective Effect of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Patients with acute myeloid leukemia (AML) during induction chemotherapy and those who receive allogeneic hematopoietic stem cell transplantation (HSCT) are at higher risk of invasive fungal infections (IFI). In the present study, we investigated whether the risk of IFI in AML patients receiving HSCT might be affected by the antifungal prophylaxis with posaconazole administered during the induction/salvage chemotherapy treatment. Between August 2001 and April 2015, 130 patients with AML received itraconazole/fluconazole (group A) and 99 received posaconazole (group B) as antifungal prophylaxis after induction/salvage chemotherapy at 7 Italian centers and all patients received fluconazole as antifungal prophylaxis after HSCT. The median duration of antifungal prophylaxis after induction/salvage chemotherapy was significantly longer for patients in group A than for those in group B (24 days versus 20 days, P  = .019). The 1-year cumulative incidence of proven/probable IFI after HSCT was 14% and 4% in group A and group B, respectively ( P  = .012). Fungal-free survival and overall survival at 1 year after HSCT were 66% and 70% in group A, and 75% and 77% in group B ( P  = .139 and P  = .302), respectively. Multivariate logistic analysis identified the use of alternative donors (matched unrelated donor: odds ratio [OR], 3.25; haploidentical/partially matched related donor: OR, 3.19), antifungal prophylaxis with itraconazole/fluconazole (OR, 3.82), and reduced-intensity conditioning (OR, 4.92) as independent risk factors for the development of IFI after HSCT. In summary, the present study suggests that the protective effects of posaconazole during induction/salvage chemotherapy for AML patients may have long-lasting benefits and eventually contribute to reduce the risk of IFI when patients undergo allogeneic HSCT

Bacterial Communities in the Embryo of Maize Landraces:Relation with Susceptibility to Fusarium Ear Rot

Locally adapted maize accessions (landraces) represent an untapped resource of nutritional and resistance traits for breeding, including the shaping of distinct microbiota. Our study focused on five different maize landraces and a reference commercial hybrid, showing different susceptibility to fusarium ear rot, and whether this trait could be related to particular compositions of the bacterial microbiota in the embryo, using different approaches. Our cultivation-independent approach utilized the metabarcoding of a portion of the 16S rRNA gene to study bacterial populations in these samples. Multivariate statistical analyses indicated that the microbiota of the embryos of the accessions grouped in two different clusters: one comprising three landraces and the hybrid, one including the remaining two landraces, which showed a lower susceptibility to fusarium ear rot in field. The main discriminant between these clusters was the frequency of Firmicutes, higher in the second cluster, and this abundance was confirmed by quantification through digital PCR. The cultivation-dependent approach allowed the isolation of 70 bacterial strains, mostly Firmicutes. In vivo assays allowed the identification of five candidate biocontrol strains against fusarium ear rot. Our data revealed novel insights into the role of the maize embryo microbiota and set the stage for further studies aimed at integrating this knowledge into plant breeding programs

Management of Invasive Fungal Infections in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: The Turin Experience

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are exposed to an increased risk of invasive fungal infections (IFIs) due to neutropenia, immunosuppressive treatments, graft-versus-host disease (GvHD) and incomplete immune reconstitution. Although clinical benefit from antifungal prophylaxis has been demonstrated, IFIs remain a leading cause of morbidity and mortality in these patients. In the last decades, attention has also been focused on potential risk factors for IFI to tailor an antifungal prevention strategy based on risk stratification. AIM OF THE STUDY: This retrospective single-center study aimed to assess the epidemiology and the prognostic factors of IFI in a large cohort of allo-HSCT patients. METHODS: Between January 2004 and December 2020, 563 patients with hematological malignancies received an allo-HSCT at the Stem Cell Transplant Unit in Turin: 191 patients (34%) received grafts from a matched sibling donor, 284 (50.5%) from a matched unrelated donor, and 87 (15.5%) from an haploidentical family member. The graft source was peripheral blood in 81.5% of the patients. Our policy for antifungal prophylaxis included fluconazole in matched related and unrelated donors, while micafungin was administered in patients receiving haploidentical transplant. According to this practice, fluconazole was administered in 441 patients (79.6%) and micafungin in 62 (11.2%), while only 9 patients received mold-active prophylaxis. Galactomannan testing was routinely performed twice a week; patients with persisting fever unresponsive to broad spectrum antibiotics were evaluated with lung high-resolution computed tomography (HRCT) scan. In case of imaging suggestive of IFI, bronchoalveolar lavage (BAL) was performed whenever feasible. STATISTICAL ANALYSIS: Only probable/proven IFI (PP-IFI) occurring during the first 12 months after transplant have been evaluated. IFIs were classified as probable or proven according to the new revised European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) consensus criteria. Multivariate competing risk regression, binary logistic, and proportional hazard models were performed to identify risk factors for PP-IFI. RESULTS: A total of 58 PP-IFIs (n = 47 probable; n = 11 proven) occurred in our patients resulting in a cumulative incidence of 4.1%, 8.1%, and 9.6% at 30, 180, and 365 days, respectively. Molds were the predominant agents (n = 50 Aspergillus; n = 1 Mucor), followed by invasive candidemia (n = 5 non-albicans Candida; n = 1 Candida albicans; n = 1 Trichosporon). Lung was the most frequent site involved in patients with mold infections (47/51, 92.2%). Median time from HSCT to IFI was 98.44 days (0–365 days). Only 34.5% of patients with IFI were neutropenic at the time of infection. The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8% vs. non-IFI, 54.6%; p < 0.001). IFI-related mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in patients with proven IFI. Multivariate competing risk regression revealed that donor type was the factor significantly associated to the risk of IFI [subdistribution hazard ratio (SDHR), 1.91, IC 1.13–3.20; p = 0.015]. BAL was informative in a consistent number of cases (36/57, 63.2%) leading to the identification of fungal (21), bacterial (4), viral (3), and polymicrobial (8) infections. Overall, 79 patients (14%) received a diagnostic-driven treatment, and 63 patients (11.2%) received a fever-driven treatment. Liposomal amphoteric B was the drug used in the majority of patients receiving diagnostic-driven therapy (30/79, 38%), while caspofungin was administered more frequently in patients who received a fever-driven strategy (27/63, 42.9%). CONCLUSION: According to our experience, a non-mold active prophylaxis in patients undergoing allo-HSCT is feasible when combined with an intensive diagnostic work-up including CT scan and BAL. BAL performed at the onset of the disease may provide informative results in most patients. A diagnostic-driven treatment strategy may contribute to limit the use of costly antifungal therapies

Mind-body relationships in elite apnea divers during breath holding: a study of autonomic responses to acute hypoxemia

The mental control of ventilation with all associated phenomena, from relaxation to modulation of emotions, from cardiovascular to metabolic adaptations, constitutes a psychophysiological condition characterizing voluntary breath-holding (BH). BH induces several autonomic responses, involving both autonomic cardiovascular and cutaneous pathways, whose characterization is the main aim of this study. Electrocardiogram and skin conductance (SC) recordings were collected from 14 elite divers during three conditions: free breathing (FB), normoxic phase of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features describing signal dynamics between the three experimental conditions: from heart rate variability (HRV) features (in time and frequency-domains and by using nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main result of the study rises by applying a Factor Analysis to the subset of features significantly changed in the two BH phases. Indeed, the Factor Analysis allowed to uncover the structure of latent factors which modeled the autonomic response: a factor describing the autonomic balance (AB), one the information increase rate (IIR), and a latter the central nervous system driver (CNSD). The BH did not disrupt the FB factorial structure, and only few features moved among factors. Factor Analysis indicates that during BH (1) only the SC described the emotional output, (2) the sympathetic tone on heart did not change, (3) the dynamics of interbeats intervals showed an increase of long-range correlation that anticipates the HPBH, followed by a drop to a random behavior. In conclusion, data show that the autonomic control on heart rate and SC are differentially modulated during BH, which could be related to a more pronounced effect on emotional control induced by the mental training to BH

Sorafenib maintenance after hematopoietic stem cell transplantation improves outcome of FLT3-ITD-mutated acute myeloid leukemia

In a retrospective analysis, 21 acute myeloid leukemia patients receiving single-agent sorafenib maintenance therapy in complete remission (CR) after hematopoietic stem cell transplantation (HSCT) were compared with a control group of 22 patients without maintenance. Sorafenib was initiated a median of 3 months (IQR: 2.3–3.5) after allogeneic HSCT with a median daily dosage of 400 mg (range: 200–800) orally, and lasted a median of 11.3 months (IQR: 3.3–24.4). No significant increase in graft versus host disease or toxicity was observed. Adverse events were reversible with dose adjustment or temporary discontinuation in 19/19 cases. With a median follow-up of 34.7 months (IQR: 16.9–79.5), sorafenib maintenance significantly improved cumulative incidence of relapse (p = 0.028) as well as overall survival (OS) (p = 0.016), especially in patients undergoing allogeneic HSCT in CR1 (p < 0.001). In conclusion, sorafenib maintenance after allogeneic HSCT is safe and may improve cumulative incidence of relapse and OS in FLT3–ITD-mutated AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12185-022-03427-4