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Backside power delivery network (BSPDN) has gained much attention due to its potential to independently optimize signal and power routing. In this work, long slit nano through silicon vias (nTSVs) is used for high-density connections between frontside (FS)-patterned buried power rails (BPRs) and orthogonally patterned metal rails on the wafer backside (BS). These nTSVs are in situ patterned on top of BPR with self-alignment using FS lithography, and the length of the slits can also be tuned. This design relaxes overlay requirements for BS patterning that are typically stringent due to wafer grid distortions during bonding. Additionally, extreme wafer thinning stopping on a 10 nm Si0.75Ge0.25 etch stop layer (ESL) is enabled using an optimized thinning sequence with excellent total thickness variation (TTV) control. For the first time, low resistance barrier-free Molybdenum (Mo)-filled nTSVs are demonstrated, confirming the potential for further scaling compared to TiN/W-filled counterparts.

Electron-spin qubits are among the most promising platforms for the realization of a large-scale quantum computer. Physical limitations dictate their operation at cryogenic temperatures, in practice often well below 1 K. This requirement implies the employment of a refrigerator featuring long cooldown times and the need for die packaging, thereby strongly limiting the number of devices that can be measured simultaneously. In our work, we evaluate traditional transistor metrics to enable fast wafer-level screening of electron-spin qubit devices above cryogenic temperatures. To the best of our knowledge, a clear link between quantum dot metrics measured below 2 K and traditional transistor metrics measured at higher temperatures has not yet been identified. In this letter, we study the correlation between 10 mK measurements in the few-electron regime, and traditional transistor metrics at different temperatures. We observe a strong correlation up to 77 K, while correlations at higher temperatures are much less pronounced. We analyze this poor correlation via room-temperature TCAD simulations, showing that the underlying physics changes due to a considerable contribution of the substrate current to the device’s off current above 77 K.

To describe the genome of Achromobactergenogroup 20 and explore the presence of resistance determinants.

ABSTRACTIntroductionAvailable treatments for colorectal cancer are limited. However, in the last few years several advances and new treatment options became available and expanded the continuum of care in metastatic colorectal cancer (mCRC).Areas coveredFruquintinib, a tyrosine kinase inhibitor, has been shown to be effective in heavily pretreated mCRC progressing to trifluridine-tipiracil (FTD/TPI) or regorafenib or both. Preclinical studies have shown that fruquintinib inhibits with high selectivity VEGFR 1-2-3, leading to a blockade in angiogenesis process, but also acts, with weak inhibition, on RET, FGFR-1, and c-kit kinases. Fruquintinib demonstrated good efficacy and tolerance in chemorefractory mCRC in two phase III trial: FRESCO and FRESCO 2. These results led to FDA approval of fruquintinib for pretreated mCRC patients who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.Expert opinionFruquintinib is a valid therapeutic option for heavily pretreated mCRC patients. However, an optimal sequence of treatments is yet to be defined. In this review, we propose an algorithm for later lines of treatment to integrate fruquintinib as a standard of care together with the new therapeutic combinations that recently showed clinical benefit for chemorefractory mCRC, in both molecularly selected (e.g. KRASG12Cor HER2 amplification) and in non-oncogenic driven patients.

This paper analyzes how changes in the firing-costs gap between permanent and temporary workers affect firms’ TFP in a dual labour market. We argue that, under plausible conditions, firms’ temp-to-perm conversion rates go down when this gap increases. Temporary workers respond to lower conversion rates by exerting less effort, while firms react by providing less paid-for training. Both channels lead to a decline in TFP. We test these implications in a large panel of Spanish manufacturing firms from 1991 to 2005, looking at the effects of three labour market reforms which entailed substantial changes in the firing-costs gap. Our empirical findings provide some support for the above-mentioned mechanism.

Background/Aim:In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group’s 25 years worth of experience. Methods:We retrospectively reviewed all GFR investigations in 2,891 patients, between 1992 and 2016, as part of 37 clinical trials coordinated by our group. Subjects with disparate renal diseases, kidney transplant recipients, and living donors – all with different renal function categories – were included in the surveyed clinical trials. Results:During 15,147 GFR measurements, only one treatment-related event of moderate intensity was identified. Flushing, urticaria, and itching were observed in a diabetic patient a few minutes after iohexol administration during the first GFR measurement. The event recovered without sequelae after intravenous injection of methylprednisolone sodium succinate. The patient was not hospitalized and the event was categorized as non-serious. Eight additional non-serious events observed closely following iohexol injection were considered as not related to treatment. Thus, independent of disease conditions and GFR categories, the overall rate of treatment-related events was 0.0066%. Conclusion:Iohexol administration for GFR measurement is a safe procedure, even in repeated investigations in the same subject, that should be adopted in clinical research and, when needed, also in clinical practice.

AbstractIntroduction:Effective response to a mass-casualty incident (MCI) entails the activation of hospital MCI plans. Unfortunately, there are no tools available in the literature to support hospital responders in predicting the proper level of MCI plan activation. This manuscript describes the scientific-based approach used to develop, test, and validate the PEMAAF score (Proximity, Event, Multitude, Overcrowding, Temporary Ward Reduction Capacity, Time Shift Slot [Prossimità, Evento, Moltitudine, Affollamento, Accorpamento, Fascia Oraria], a tool able to predict the required level of hospital MCI plan activation and to facilitate a coordinated activation of a multi-hospital network.Methods:Three study phases were performed within the Metropolitan City of Milan, Italy: (1) retrospective analysis of past MCI after action reports (AARs); (2) PEMAAF score development; and (3) PEMAAF score validation. The validation phase entailed a multi-step process including two retrospective analyses of past MCIs using the score, a focus group discussion (FGD), and a prospective simulation-based study. Sensitivity and specificity of the score were analyzed using a regression model, Spearman’s Rho test, and receiver operating characteristic/ROC analysis curves.Results:Results of the retrospective analysis and FGD were used to refine the PEMAAF score, which included six items–Proximity, Event, Multitude, Emergency Department (ED) Overcrowding, Temporary Ward Reduction Capacity, and Time Shift Slot–allowing for the identification of three priority levels (score of 5-6: green alert; score of 7-9: yellow alert; and score of 10-12: red alert). When prospectively analyzed, the PEMAAF score determined most frequent hospital MCI plan activation (>10) during night and holiday shifts, with a score of 11 being associated with a higher sensitivity system and a score of 12 with higher specificity.Conclusions:The PEMAAF score allowed for a balanced and adequately distributed response in case of MCI, prompting hospital MCI plan activation according to real needs, taking into consideration the whole hospital response network.

Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients’ gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41–0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54–0.74), P-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48–0.80) in women and only 0.78, (95%CI 0.67–0.92) in men, P-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness.

We address the problem of detecting distribution changes in a novel batch-wise and multimodal setup. This setup is characterized by a stationary condition where batches are drawn from potentially different modalities among a set of distributions in $\mathbb {R}^{d}$ represented in the training set. Existing change detection (CD) algorithms assume that there is a unique—possibly multipeaked—distribution characterizing stationary conditions, and in batch-wise multimodal context exhibit either low detection power or poor control of false positives. We present MultiModal QuantTree (MMQT), a novel CD algorithm that uses a single histogram to model the batch-wise multimodal stationary conditions. During testing, MMQT automatically identifies which modality has generated the incoming batch and detects changes by means of a modality-specific statistic. We leverage the theoretical properties of QuantTree to: 1) automatically estimate the number of modalities in a training set and 2) derive a principled calibration procedure that guarantees false-positive control. Our experiments show that MMQT achieves high detection power and accurate control over false positives in synthetic and real-world multimodal CD problems. Moreover, we show the potential of MMQT in Stream Learning applications, where it proves effective at detecting concept drifts and the emergence of novel classes by solely monitoring the input distribution.

We present a global–local full‐waveform inversion (FWI) of surface waves to estimate a high‐resolution shear wave velocity model of the near‐surface at the site of Grenoble (France). The seismic data we use have been acquired in the framework of the InterPACIFIC project. A first attempt is made by employing the multichannel analysis of surface waves (MASW) to invert the fundamental modes of Rayleigh waves. This inversion is solved through a global optimization driven by the neighbourhood algorithm. However, the limiting 1D assumption, together with the severely ill‐posedness of the MASW inversion motivate us to exploit all the information content of the recorded Rayleigh waves (i.e., travel‐times and amplitudes) by implementing a global–local FWI approach. We first perform a global FWI in which a genetic algorithm (GA) is used to minimize the L2 norm difference between observed and simulated seismic waveforms up to 30 Hz. This inversion employs a two‐grid scheme in which the subsurface is described by a fine grid input to the forward modelling, whereas the unknowns are defined on a coarse grid. A bilinear interpolation brings the coarse‐grid model into the fine grid. To accelerate the convergence, two strategies are considered; offset marching and frequency marching. Then, the long‐wavelength velocity profile provided by the GA inversion is used as the starting point for a local FWI for further refinement of the predicted model. In this case, we employ a frequency‐marching strategy up to a maximum frequency of 60 Hz. Both the global and local approaches use a finite difference code for the forward computation. Despite the limited a priori information infused into the inversion framework, the presented global–local FWI scheme provides reliable results as demonstrated by the good match between recorded and predicted seismograms and by the agreement of the estimated velocity with both nearby borehole data and stratigraphic information on the study site. Our global–local strategy also achieves better data fitting and improved matching with the available borehole data with respect to the velocity profile estimated when the local FWI is started from the MASW predictions.

AbstractObjectivesThe aims of this study were to explore the knowledge of EMS physicians (EMSPs) on the legal aspects related to the management of prehospital psychiatric emergencies, assess their degree of comfort, and measure their perceived communication skills.MethodsA survey was distributed to the 376 EMSPs working in the prehospital setting in Lombardy, Italy. Knowledge of medico-legal aspects was measured through multiple-choice questions; the Comfort Score (CS) and perceived Communication Skills Score (CSS) were calculated using Likert Scale questions. CS ranged from 11 points (lowest) to 44 (highest); CSS ranged from 8 points (lowest) to 32 (highest).ResultsA total of 272 EMSPs answered the survey (RR= 72.3%); 45.2% were women. Mean age was 45.76 years (SD 8.8). Mean percentage of correct knowledge test answers was 52.4 (SD 12.3); 81.3% believed to have little knowledge of the Italian legislation regarding this topic. Mean CS was 29.3 (SD 5.5); mean CSS was 19.1 (SD 3.9). A higher percentage of correct answers in the knowledge test was associated with lower CS (P =0.019). Higher self-appraised knowledge of the Italian legislation was associated with higher CS (P < 0.001) and higher CSS (P <0.001).ConclusionsThese findings should prompt policy makers to ensure proper training and support for EMSPs in the matter of prehospital psychiatric emergency management.

The article discusses DEM's profile wire rolling technology for copper and aluminum. DEM supplies equipment and complete lines for the production of copper and aluminum wire, which are used in various applications such as oil transformers, motors, generators, EV automotive, supply lines, and power distribution. DEM's rolling technology offers higher speed, perfect coiling, outstanding tolerance, and dimensional and surface quality. The article also mentions a newly developed rolling module for flat wire used in e-mobility power engines. DEM has developed various technological packages for profile wire rolling, including automatic loading and unloading of spools, in-line cleaning of tools, stand continuous shift for uniform tool wear, and fully automatic edging stands. DEM also offers a digital platform called "Wire Up" for monitoring, automatic alerts, trouble-shooting, maintenance, analysis, process modeling, and spare parts management. DEM is a mechanical engineering company based in Italy that specializes in wire and reinforcing steel processing equipment. [Extracted from the article]

We report on scaled finFETs built with a novel routing scheme wherein devices are connected via buried power rails (BPRs) from both wafer sides, with tight variability and matching control. On the wafer’s frontside (FS), M1 lines (FSM1) are connected through V0 vias to M0A lines which are then linked to BPR lines by vias called VBPR while also contacting directly the device’s S/D-epi. As for gate wiring, to enable in this work its access from both wafer sides, gate is also connected to BPR via V0 landing on it and on a neighboring M0A line set only on field-oxide. A single-step metallization for M0A and VBPR is preceded by in situ preclean(s) optimized for improved BPR-VBPR contact interface and ${R}_{\text {ext}}$ , as confirmed electrically and by physical analysis. After FS processing, wafer flipping, bonding, and extreme thinning, highly scaled, ~323 nm deep nano-through-Si-vias (nTSVs) land on BPR, with tight overlay control and unchanged BPR resistance [26%–29% lower with improved tungsten (W)-fill], connecting them to the first backside (BS) metal level (BSM1). By moving the power delivery network to the BS (BSPDN), besides alleviating FS routing congestion, considerably smaller dynamic and static IR drop values are predicted from on- chip power heat maps generated for a low power 64-bit CPU at 2-nm design rules: 82% and 96% less worst-case values versus a reference configuration, respectively. P/NMOS show similar or even superior ${I}_{ \mathrm{\scriptscriptstyle ON}}$ – ${I}_{ \mathrm{\scriptscriptstyle OFF}}$ after BS processing and extra anneal(s) added for ${V}_{T}$ recovery, mobility and bias temperature instability (BTI) improvement—up to 8%/15% higher ${I}_{ \mathrm{\scriptscriptstyle ON}}$ linked to anneal selection.

Expensive forward model evaluations and the curse of dimensionality usually hinder applications of Markov chain Monte Carlo algorithms to geophysical inverse problems. Another challenge of these methods is related to the definition of an appropriate proposal distribution that simultaneously should be inexpensive to manipulate and a good approximation of the posterior density. Here we present a gradient‐based Markov chain Monte Carlo inversion algorithm that is applied to cast the electrical resistivity tomography into a probabilistic framework. The sampling is accelerated by exploiting the Hessian and gradient information of the negative log‐posterior to define a proposal that is a local, Gaussian approximation of the target posterior probability. On the one hand, the computing time to run the many forward evaluations needed for both the data likelihood evaluation and the Hessian and gradient computation is decreased by training a residual neural network to predict the forward mapping between the resistivity model and the apparent resistivity value. On the other hand, the curse of dimensionality issue and the computational effort related to the Hessian and gradient manipulation are decreased by compressing data and model spaces through a discrete cosine transform. A non‐parametric distribution is assumed as the prior probability density function. The method is first demonstrated on synthetic data and then applied to field measurements. The outcomes provided by the presented approach are also benchmarked against those obtained when a computationally expensive finite‐element code is employed for forward modelling , with the results of a gradient‐free Markov chain Monte Carlo inversion, and also compared with the predictions of a deterministic inversion. The implemented approach not only guarantees uncertainty assessments and model predictions comparable with those achieved by more standard inversion strategies, but also drastically decreases the computational cost of the probabilistic inversion, making it similar to that of a deterministic inversion.

AbstractObjectiveAsymmetric warfare, conflict and terrorist attacks involving children raise concerns regarding the preparedness to respond to mass casualty incidents involving pediatric patients. The objective of this project was to assess the resources available in the metropolitan Milan area to develop a priority dispatch plan for a mass casualty incident with pediatric patients.MethodsA focused search of the medical literature and clinical guidelines established a minimal standard requirements of care of pediatric patients involved in an MCI to determine the surge capabilities in terms of number of patients and severity of injuries for each study hospital in the metropolitan Milan area.ResultsThe hospitals that took part in the study were either adult trauma centers or pediatric hospitals in the metropolitan Milan area. The overall surge capability identified was of 40-44 pediatric patients involved in an MCI involving pediatric patients, distributed based on age and severity and based on the hospital resources and expertise.ConclusionsThe findings from the metropolitan Milan area shows the basis for non-Pediatric Trauma Center adult and pediatric hospitals to work in synergy to develop MCI response plans involving pediatric patients. Simulations exercises will need to be carried out to evaluate and validate the plans.