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AbstractIn this study, we address interpersonal violence during the transition between the Middle and the Late Formative periods in the Central Andes, a critical period of political disintegration, hypothesized population pressure, and reorganization of the belief systems that is poorly known from a bioarchaeological viewpoint. Our objective is to understand the nature of the violence and associated factors in this context based on a detailed description of skeletal trauma in 67 well-preserved individuals (20 adolescents and adults and 47 subadults) recovered from Quebrada Chupacigarro cemetery (500–400 BC); this site is located in the middle valley of Supe on the Peruvian north-central coast. To detect patterns and potential causes, we registered the prevalence of traumatic injury according to age, sex, anatomic location, mechanisms (blunt, sharp, mixed, etc.), timing (antemortem or perimortem), and manner (inflicted or accidental). The results show a high prevalence of fractures in the whole population, but especially in adolescents and adults. Eighty percent of the adolescents and adults perished due to the intentional trauma and show patterns that suggest repetitive episodes of interpersonal violence. Perimortem injuries in the skull, face, and thorax are compatible with lethal interpersonal violence. The findings support a probable scenario of intercommunity violence in the middle valley of Supe around 500–400 BC.

AlbaSat is a 2-Unit CubeSat which is being developed by a student team at the University of Padova. The Alba project aims to design, build, test, launch, and operate the first student CubeSat of the University of Padova, featuring four different payloads. The first goal is to collect data regarding the debris environment in Low Earth Orbit, the second goal is the study of the satellite vibrations, the third one is about CubeSat attitude determination through laser ranging technology, and the fourth goal concerns satellite laser and quantum communication. The Alba CubeSat mission has been selected by the European Space Agency to join the Fly Your Satellite! Design Booster program in December 2022. This paper presents the feasibility study of the Alba CubeSat mission reproduced in the framework of the “Space Systems Laboratory” class of Master of Science in Aerospace Engineering at the University of Padova. In the beginning, a mission requirements definition was conducted. After that, the mission feasibility was considered, with preliminary requirements verification to assess the ability of the spacecraft to survive the space environment, including compliance with Debris Mitigation Guidelines, ground station visibility and minimum operative lifetime evaluation. The Alba mission sets a base for a better understanding of the space environment and its interaction with nanosatellites, and an improvement of the accuracy of debris models. Furthermore, this paper, describing the educational experience and the results achieved, will provide a useful example for future students’ studies on CubeSat mission design.

MmWaves have been envisioned as a promising direction to provide Gbps wireless access. However, they are susceptible to high path losses and blockages, which can only be partially mitigated by directional antennas. That makes mmWave networks coverage-limited, thus requiring dense deployments. Integrated access and backhaul (IAB) architectures have emerged as a cost-effective solution for network densification. Resource allocation in mmWave IAB networks must face big challenges originated by heavy temporal dynamics, such as intermittent links caused by user mobility and blockages from moving obstacles. This makes it extremely difficult to find optimal and adaptive solutions. In this article, exploiting the distributed structure of the problem, we propose a Multi-Agent Reinforcement Learning (MARL) framework to optimize user throughput via flow routing and link scheduling in mmWave IAB networks characterized by mobile users and obstacles. The proposed approach implicitly captures the environment dynamics, coordinates the interference, and manages the buffer levels of IAB relay nodes. We design different MARL components, respectively for full-duplex and half-duplex networks. In addition, we propose an online training algorithm, which addresses the feasibility issues of practical systems, especially the communication and coordination among RL agents. Numerical results show the effectiveness of the proposed approach.

Since COVID-19's onset last year, children have flocked to their computers, tablets, and phones for just about everything, from gaming to socializing to schooling. Screens have become their primary window [...]

Current literature regarding cancer risk in rheumatic and musculoskeletal diseases (RMDs) is particularly poor and controversial, even though the incidence of malignancy in some patients with RMDs is considered to be increased compared with the general population. Malignancy may be a major comorbidity in subjects with spondyloarthritis (SpA) as the result of multifactorial mechanisms, from disease pathogenesis to the iatrogenic effect of immunomodulating drugs. Several recommendations for screening and management of cancer risk have been developed in recent years with the aim of improving the different outcomes in these patients. The goal of this narrative review is to provide an overview of the currently available evidence on the risk of malignancy connected with RMDs and examine the association of SpA with cancer and the potential impact of its treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs on development of malignancy.

Dietary intake to trace elements may represent the most relevant source of exposure for the general, non-occupationally population, but some of them have been rarely evaluated. We measured content of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples through inductively coupled plasma mass spectrometry. We estimated their dietary intake using a validated semi-quantitative food frequency questionnaire collected from a population of the Emilia-Romagna Region in Northern Italy. We compared our estimates with tolerable upper intake levels reported by international agencies and we assessed the non-carcinogenic risk through calculation of total hazard quotient for each trace element according to the US-EPA approach. Overall, estimates of their dietary intake were substantially similar to those reported from other countries, and they fell below the tolerable upper intake levels provided by international agencies. The total hazard quotient for each trace element was below 1. Our findings provide updated estimates of food levels and dietary intake of trace elements far frequently evaluated in a sample of Italian adult consumers. They also suggest that any non-carcinogenic risk associated with intake of investigated trace elements may be ruled out in our population.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus’ expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3–6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidumendemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidumsubspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

Thanks to its capability of manipulating electromagnetic signals, the reconfigurable intelligent surface (RIS) is gaining momentum in alleviating the impact of blockages on mmWave signals, by providing redirected transmission paths. However, obstacles can also inevitably appear in the redirected paths. This can be solved by installing multiple RISs and switching among them. In this letter, for the first time, we adaptively switch among RISs for a mobile user in real time to optimize its achievable rate, without need for a priori knowledge on potential obstacles. We present an actor-critic based approach to learn unknown obstacles and variational spatial correlations originated by the user mobility, which is followed by the analysis on ergodic achievable rate. Experimental results have shown that the approach can achieve rates about 15% less than the optimum and 76% more than the state-of-the-art.

During the COVID-19 pandemic, Latin American and Caribbean countries implemented stringent public health and social measures that disrupted economic and social activities. This study used an integrated model to evaluate the epidemiological, economic, and social trade-offs in Argentina, Brazil, Jamaica, and Mexico throughout 2021. Argentina and Mexico displayed a higher gross domestic product (GDP) loss and lower deaths per million compared with Brazil. The magnitude of the trade-offs differed across countries. Reducing GDP loss at the margin by 1 percent would have increased daily deaths by 0.5 per million in Argentina but only 0.3 per million in Brazil. We observed an increase in poverty rates related to the stringency of public health and social measures but no significant income-loss differences by sex. Our results indicate that the economic impact of COVID-19 was uneven across countries as a result of different pandemic trajectories, public health and social measures, and vaccination uptake, as well as socioeconomic differences and fiscal responses. Policy makers need to be informed about the trade-offs to make strategic decisions to save lives and livelihoods.

This article discusses the denial of the right to a fair trial for Turkish lawyers who have been investigated, accused, and convicted due to their alleged links with terrorist organizations. The trials against members of the Turkish association CHD have attracted significant attention, with international organizations sending observers to attend the hearings and visit the lawyers in prison. The article highlights numerous violations of international law guaranteeing the role of lawyers and the right to a fair trial, including the inability to cross-examine witnesses and access incriminating evidence. The trials resulted in prison sentences for the defendants, with violations of the right to due process and the principle of ne bis in idem. The author emphasizes the importance of continued monitoring and intervention by the international legal community in cases of fundamental rights violations. [Extracted from the article]

The parasitic exploitation of WiFi signals for passive sensing purposes is a topic that is attracting considerable interest in the scientific community. In an attempt at meeting the requirements for sensor compactness, easy deployment, and low cost, we resort to a noncoherent signal processing scheme that does not rely on the availability of a reference signal and relaxes the constraints on the sensor hardware implementation. Specifically, with the proposed strategy, the presence of a moving target echo is determined by detecting the amplitude modulation that it produces on the direct signal transmitted from the WiFi access point. We investigate the target discrimination capability of the resulting sensor against the competing interference background and we theoretically characterize the impact of undesired amplitude fluctuations in the received signal that are determined by causes other than the superposition of the target echo, thereby including the waveform properties. Hence, we propose different solutions to address the limitations identified, characterized by different complexities, and we investigate their advantages and drawbacks. The conceived signal processing schemes are thoroughly validated on both simulated and experimental data, collected in different operational scenarios.

Background: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p= 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p= 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p= 0.001; PTH at target: 18% vs 37% p= 0.001; PTH > 300 pg/ml 23% vs 42% p= 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p= 0.0001), calcimimetics (34% vs 14%, p= 0.0001) and phosphate binders (77% vs 66%, p= 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract:

Mining activity affects the vegetation and soils of the ecosystems. However, the effects of mining activity on saxicolous lichen communities are less concerned. Thus, the aim of this study was to characterize saxicolous lichen communities in three basins (Vis-Vis River basin, Poteros River basin, and Capillitas River basin) surrounding metalliferous mining projects of different types of operation and at different stages of exploitation. A large-scale mine (Bajo de la Alumbrera) with more than 25 a of open-pit mining located in the Vis-Vis River basin (CRV). A pre-exploitation mine (Agua Rica) located in the Poteros River basin (CRP), and a small-scale mine (Minas Capillitas) with more than 160 a of underground mining located in the Capillitas River basin (CAC). In each basin, species richness, cover, and frequency of lichen communities were measured on 40 rock outcrops. Also, explanatory variables were recorded, i.e., altitude, slope, aspect, vegetation cover, rock, and soil cover around the rocky area sampled. Richness and total cover of lichen communities were analysed using linear models, and species composition was explored using multivariate ordination analysis. Results showed that a total of 118 lichen species were identified. The species richness differed among basins and the lichen composition present in areas close to mining sites responded mainly to basins, altitude, and microsite variables. The lichen cover showed no difference among basins, but it changed under different rock and vegetation cover. It was not possible to quantify the effects of mining activity on species richness and composition. However, the low richness values found in the downstream of Minera Alumbrera could be associated with the negative impact of open-pit mining. Moreover, the effects of large-scale mining activity on lichen communities needs more investigation.

For patients with acute myeloid and lymphoblastic leukaemia (AML/ALL) lacking a matched sibling or unrelated donor, haploidentical stem cell transplantation (HAPLO-SCT) is increasingly used. However, available data on the treatment of relapse after HAPLO-SCT, including feasibility and efficacy of a second HAPLO-SCT (HAPLO-SCT2), is scarce. Hence, adults with AML/ALL, that had undergone HAPLO-SCT2 without ex-vivo manipulation after haematologic relapse from HAPLO-SCT1 were selected for a retrospective registry analysis. Eighty-two patients (AML, n= 63, ALL, n= 19, median follow-up: 33 months) were identified. Engraftment rate was 87%. At day +180, cumulative incidences of acute GvHD II-IV°/chronic GvHD were 23.9%/22.6%, respectively. Two-year overall survival/leukaemia-free survival (OS/LFS) were 34.3%/25.4%; 2-year non-relapse mortality (NRM) and relapse incidence (RI) were 17.6% and 57%. Leukaemia was the most frequent cause of death. Separated by disease, 2-year OS/LFS/NRM/RI were 28.7%/22.3%/16.2%/61.6% in AML, and 55.3%/38.4%/23.5%/38.2% in ALL patients. In a risk-factor analysis among patients with AML, stage at HAPLO-SCT1 and HAPLO-SCT2, and interval from HAPLO-SCT1 to relapse significantly influenced outcome. Our data demonstrate that HAPLO-SCT2 is a viable option in acute leukaemia relapse after HAPLO-SCT1. Engraftment, toxicity, risk factors and long-term outcome are comparable to data reported after allo-SCT2 in a matched donor setting.

Oxetanes are strained heterocycles with unique properties that have triggered significant advances in medicinal chemistry. However, their synthesis still presents significant challenges that limit the use of this class of compounds in practical applications. In this Letter, we present a methodology that introduces a new synthetic disconnection to access oxetanes from native alcohol substrates. The generality of the approach is demonstrated by the application in late-stage functionalization chemistry, which is further exploited to develop a single-step synthesis of a known bioactive synthetic steroid derivative that previously required at least four synthetic steps from available precursors.

Gait smoothness, perceived when a person walks continuously and uninterruptedly, is associated with an undisrupted gait pattern, good sensorimotor control, and a lower risk of falling. The spectral arc length (SPARC) is a quantitative metric proposed for the evaluation of movement smoothness from the signal obtained by wearable sensors. In this small exploratory case–control study, older persons with and without a history of injurious falls underwent a turn-test while wearing an accelerometer: gait smoothness was estimated by calculating SPARC during the straight and turning phases. Cases seemed to exhibit lower SPARC values during the turning phase, in comparison with control.

Multicenter ventricular tachycardia (VT) ablation studies have shown poorer outcomes compared with single-center experiences. This difference could be related to heterogeneous mapping and ablation strategies.

A light-driven protocol for the synthesis of 2,3-dihydrobenzofurans under mild conditions is reported. Specifically, the cascade process is initiated by the photochemical activity of allyl-functionalized phenolate anions, generated in situupon deprotonation of the corresponding phenols. The reaction proceeds rapidly with reaction times as low as 35 min, delivering a wide range of densely functionalized products (20 examples, yields up to 69%). Mechanistic studies have also been performed providing convincing evidence for the photochemical formation of carbon-centered radical species. A cascade reaction pathway involving a tandem atom transfer radical addition (ATRA) and an intramolecular nucleophilic substitution (SN) process is proposed to occur.

This study aimed to describe the intellectual profile based on the Wechsler Intelligence Scale for Children 4th edition (WISC‐IV) in children with self‐limited epilepsy with centrotemporal spikes (SeLECTS), with an attempt to define possible predictive epilepsy‐related variables of cognitive performance. The WISC‐IV was assessed in 161 children with SeLECTS and their cognitive profiles were compared to a matched sample of healthy control children. Children with SeLECTS performed within normal range across all indices, demonstrating particular strength based on the Perceptual Reasoning Index. Compared to healthy control children, we observed a significant difference in performance based on the Full Scale Intelligence Quotient, Verbal Comprehension Index and Processing Speed Index. Regarding epilepsy‐related variables, earlier onset of epilepsy, use of anti‐seizure medications, the presence of neurodevelopmental disorders, a higher frequency of seizures, and a longer treatment duration were associated with an overall lower level of performance. Children with SeLECTS performed within the average range for cognitive assessment based on the WISC‐IV, demonstrating that children had normal levels of global intelligence. However, compared to healthy control children, children with SeLECTS showed a slightly lower level of performance. Reasoning skills represented the relative strengths in children with SeLECTS. Predictors of intellectual performance in patients with SeLECTS include epilepsy‐related variables and neurodevelopmental comorbidities.

ABSTRACTSince birth, infants have been immersed in a social environment, often surrounded by artificial-intelligent-agents (AIAs). However, there is a paucity of work on infants’ psychophysiological responses, and their related interest, when interacting with AIAs. Here, the infants’ psychophysiological responses during interactions with an embodied robot and a virtual human/avatar presented on a screen are investigated. The experimental paradigm consists of a robot producing socially communicative gestures to babies as compared to a virtual human producing socially communicative gestures and linguistic interactions, such as linguistic nursery rhymes in American Sign Language. Psychophysiological responses were measured using thermal infrared imaging technology that tracks changes in cutaneous temperature, enabling contactless investigation of human autonomic functions. Crucially, it permits first-time inferences about changes in infants’ psychological, attentional, and emotional engagement in relation to agents and events in the world around them. Thermal signals analysis revealed a statistically significant difference in the infants’ physiological response to robot and avatar interactions indicating important differences in each agent’s ability to engage infants. Understanding infants’ psychophysiological responses to AIAs during the first year of life, which is a crucial period for human learning, lays bare how AIAs may impact infants’ emotional, social, and language learning and higher cognitive growth.

The formation of carbon–carbon bonds via the intermolecular addition of alkyl radicals to alkenes is a cornerstone of organic chemistry and plays a central role in synthesis. However, unless specific electrophilic radicals are involved, polarity matching requirements restrict the alkene component to be electron deficient. This limits the scope of a fundamentally important carbon–carbon bond forming process that could otherwise be more universally applied. Herein, we introduce a polarity transductionstrategy that formally overcomes this electronic limitation. Vinyl sulfonium ions are demonstrated to react with carbon-centered radicals, giving adducts that undergo in situor sequential nucleophilic displacement to provide products that would be inaccessible via traditional methods. The broad generality of this strategy is demonstrated through the derivatization of unmodified complex bioactive molecules.

Edge computing has been recently introduced to bring computational capabilities closer to end-users of modern network-based services, supporting existing and future delay-sensitive applications by effectively addressing the high propagation delay issue that affects cloud computing. However, the problem of efficiently and fairly managing the system resources presents particular challenges due to the limited capacity of both edge nodes and wireless access networks and the heterogeneity of resources and services’ requirements. To this end, we propose a techno-economic market where service providers act as buyers, securing both radio and computing resources to execute their associated end-users’ jobs while being constrained by a budget limit. We design an allocation mechanism that employs convex programming to find the unique market equilibrium point that maximizes fairness while ensuring that all buyers receive their preferred resource bundle. Additionally, we derive theoretical properties that confirm how the market equilibrium approach strikes a balance between fairness and efficiency. We also propose alternative allocation mechanisms and give a comparison with the market-based mechanism. Finally, we conduct simulations to numerically analyze and compare the performance of the mechanisms and confirm the market model's theoretical properties.

Introduction: Androgen deprivation therapy (ADT) is the key of medical treatment for advanced prostate cancer (PCa), especially in elderly patients. However, the adherence of ADT prescription to current guidelines is not optimal and must be balanced against possible side effects. Aim of this study was to evaluate the prescriptive appropriateness of ADT and ADT-related adverse events in a referral center for PCa.Methods: Five hundred fifty six patients who received an outpatient prescription for ADT from 2014 to 2018 were retrospectively identified from an administrative database. Only standard ADT was considered, including GnRH agonists, GnRH antagonists, and antiandrogens. Prescriptive appropriateness was defined according to the last European Association of Urology (EAU) guidelines. Our cohort was stratified according to age categories and patient follow-up was updated.Results: Four hundred twenty five patients were available for analysis. Mean age was 80 years; 96.3% of our patients fell in the “elderly” category. There was a predominance of GnRH agonists over the antagonists (84.9% vs 13%). 15.5% of ADTs did not have an appropriate indication according to guidelines. Patient compliance to ADT was evaluated as good in 372 (87.5%) cases. ADT-related complications were detected in 166 (39%) patients: bone, cardiovascular, and other complications were reported in 7.3%, 8.9%, and 19% of patients. Progression of disease was noted in 165 (38.8%) cases during ADT. At last follow-up, 124 (30.1%) patients were deceased.Conclusions: In a referral center, most ADT prescriptions followed EAU guidelines, but a non-negligible proportion still did not fall within these indications, exposing patients to unnecessary side effects. Compliance to ADT was generally good with a predominant use of GnRH agonists. Tolerance to ADT was fair, even if standardized reports were lacking.

Background: Several peripheral regional anaesthesia (RA) techniques are commonly used in thoracic surgery even in the absence of precise indications regarding their effectiveness on postoperative pain management.Objective: This systematic review and meta-analysis aims to describe and evaluate the relative effectiveness of different peripheral regional blocks and systemic analgesia in the context of video-assisted thoracoscopic surgery (VATS) or thoracotomy.Design: Systematic review of randomized controlled clinical trials (RCTs) with meta-analyses.Data sources: We searched PubMed and Embase for all RCTs comparing the 24 hour morphine equivalents (MMEs) consumption following peripheral regional blocks and systemic analgesia (SA).Eligibility criteria: We selected only RCTs including adult participants undergoing thoracic surgery, including esophagectomy and reporting on postoperative pain outcomes including 24 hour MMEs consumption.Results: Among the 28 randomized studies including adult participants undergoing thoracic surgery and reporting on 24 hour opioid consumption, 11 reporting a comparison of individual blocks with systemic analgesia were meta-analyzed. RA was effective for almost all peripheral blocks. Regarding intercostal block, its antalgic effect was not well evaluated SMD -1.57 (CI -3.88, 0.73). RA in VATS was more effective in reducing MMEs than thoracotomy SMD -1.10 (CI -1.78, -0.41).Conclusions: RA is a useful choice in thoracic surgery. However, it is still not possible to determine the most appropriate block in the individual surgical settings to be performed due to RCTs paucity.

Dual-energy CT helped to accurately diagnose bone stress fractures and stress reactions of the lower limb (leg, ankle, and foot) using MRI as the reference standard.

Full-Maxwell lightning strike analyses are generally computationally expensive since they require time domain simulations of complex structures in a semi-infinite vertically layered background. In this paper it is shown how Model Order Reduction can be applied to Integral Equation methods to effectively speed up such analyses. Moreover, the layered Green's function theory is applied to consider the presence of the semi-infinite layered ground region without introducing approximations or facing prohibitive modeling issues.

Selenium is an essential trace element with both beneficial and detrimental effects on health depending on dose and chemical form. Currently, there is debate on recommendations for selenium supplementation as a public health measure to improve immune function and reduce infectious disease susceptibility.

Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa.

An artificial intelligence–based computer-aided diagnosis tool improved radiologists’ and pulmonologists’ risk stratification of indeterminate pulmonary nodules on chest CT scans.

In recent years, immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab have revolutionized the treatment landscape in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, many patients do not respond to ICIs for reasons that remain largely unknown. For patients who progress on ICIs, chemotherapy and/or biologic therapies are the most widely used treatments based on the clinician’s choice, with no defined sequence strategy. We report the experience of a patient with metastatic oropharyngeal squamous cell cancer p16 and human papillomavirus-DNA positive who received chemotherapy with weekly paclitaxel after progressing on nivolumab. Our patient presented a partial response to fourth line paclitaxel, which lasted more than 2 years, with an improvement of his quality of life too. These results support the hypothesis of synergism between immunotherapy and conventional chemotherapies. Even in the setting of immune-refractory disease, immunotherapy may affect tumor immune microenvironment thus leading to a synergistic effect with conventional chemotherapy and achieving unexpected results.

THE JUDGMENT that we live in a secular society may reflect an historical aberration, a modern phenomenon, and largely an exclusively Western phenomenon, the recent judicial difficulties of Turkey's ruling [...]

Based on survey data from Italian and Japanese companies, six measurement scales are developed for practices, process, strategic guide, and capabilities for new product development as potential determinants of its financial performance, that is, attainment of profit goals and revenue goals. By employing a regression model with a country dummy variable, the differential determinants of financial goals attainment between Italian and Japanese samples are estimated. A significant difference can be found in the impact of new product development capabilities on profit goals attainment only. Then, we evaluate the level of improvement in explanatory power by dividing the pooled sample into two and enabling regression coefficients to take different values, and find no evidences of the significant improvement. Technology and marketing capabilities concerning new product development are demonstrated to be overwhelmingly important to financial performance. Keywords: New product development: Manufacturing: International comparison: Empirical research

This paper applies a number of stochastic cost frontier models to a panel data set and compares their ability to distinguish unobserved heterogeneity from inefficiency variation among firms. The main [...]