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Early periprosthetic joint infection constitutes one of the most frightening complications of joint replacement. Recently, some evidence has highlighted the potential link between dysregulation of the gut microbiota and degenerative diseases of joints. It has been hypothesized that microbiome dysbiosis may increase the risk of periprosthetic joint infection by facilitating bacterial translocation from these sites to the bloodstream or by impairing local or systemic immune responses. Although the processes tying the gut microbiome to infection susceptibility are still unknown, new research suggests that the presurgical gut microbiota—a previously unconsidered component—may influence the patient's ability to resist infection. Exploring the potential impact of the microbiome on periprosthetic joint infections may therefore bring new insights into the pathogenesis and therapy of these disorders. For a successful therapy, a proper surgical procedure in conjunction with an antibacterial concept is essential. As per the surgical approach, different treatment strategies include surgical irrigation, debridement, antibiotic therapy, and implant retention with or without polyethylene exchange. Other alternatives could be one-stage or two-stage revisions surgery. Interventions that either directly target gut microbes as well as interventions that modify the composition and/or function of the commensal microbes represent an innovative and potentially successful field to be explored. In recent times, innovative therapeutic methods have arisen in the realm of microbiome restoration and the management of gut-related ailments. These progressive approaches offer fresh perspectives on tackling intricate microbial imbalances in the gastrointestinal tract. These emerging therapies signify a shift towards more precise and individualized approaches to microbiome restoration and the management of gut-related disorders. Once a more advanced knowledge of the pathways linking the gut microbiota to musculoskeletal tissues is gained, relevant microbiome-based therapies can be developed. If dysbiosis is proven to be a significant contributor, developing treatments for dysbiosis may represent a new frontier in the prevention of periprosthetic joint infections.

We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: nephronophthisis type 1 (NPHP1) and Alström syndrome (AS). NPHP1is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance/type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis that is essential to achieve the best clinical management could be challenging.

Formation of arrays (FoA) distributed antenna technology has recently been proposed to provide 5G-like mobile satellites services in the context of the integration of nonterrestrial with terrestrial networks—the overall system goal being a sufficiently high throughput in terms of bit rate per unit area on the ground. This large distributed array configuration (resulting from the formation of many satellites each carrying its own small antenna) must be carefully engineered to provide the desired benefits. In this article, we tackle some fundamental issues related to FoA design, namely, frequency selectivity, power generation, and optimal formation configuration. Concerning frequency selectivity, we evaluate the intrinsic FoA frequency response assuming a wideband signal, and suggest how to mitigate possible impairments from a communication system perspective. Regarding power generation, we show how to decouple the functions of antenna and solar arrays to come to a power-efficient satellite configuration and design. Finally, in terms of formation optimization, we investigate a formation thinning approach with random placement of satellites on a grid, leading to a significant reduction of secondary beams in the emission of the FoA as well as fully satisfying the constraints placed by optimum power generation.

Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103+cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3−/− mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt+T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.

One of the major needs of present and future spacecraft is to fulfil highly demanding pointing requirements when performing attitude manoeuvres without losing stringent control over their flexible parts. For long-duration missions, the propellant mass is a significant portion of the overall mass budget of the satellite. The interaction between the fluid and the tank walls can lead to instability problems and even to mission failure if not properly accounted for in the design phase and control synthesis. The combined liquid–structure dynamic coupling is usually extremely difficult to model for a space system. An equivalent mechanical system is then desirable to carry out a computationally efficient simulation of the liquid behaviour inside the tank. In this paper, the 3D model of a spacecraft equipped with flexible appendages and tanks containing liquid propellant is presented. A learning-based control strategy using on-orbit available data is designed to improve the attitude tracking precision for repetitive on-orbit manoeuvres, compensating for cyclic disturbances such as liquid fuel sloshing effects. A co-simulation procedure between MSC Adams and Simulink is then carried out to test the performance of the controller. The effectiveness of the proposed control strategy is analysed and discussed, and conclusions are presented.

This article presents a two-stage approach for the processing of frequency-stacked mobile subbands. The frequency stacking is performed in the analog domain to enable the use of a wideband analog-to-digital converter (ADC), instead of employing multiple narrowband ADCs, to support multiple antenna elements for digital satellite beamforming. This analog front end provides a common broadband digital interface to the on-board processor and can be configured to support multiple satellite missions, reducing the cost of commissioning a digital processor for individual satellite missions. This article proposes a framework on the specification of digital prototype filter for the analysis of frequency-stacked mobile subbands. The computational complexity of the analysis operation, with two digital filter alternatives, are evaluated. A series of results, taken from our European Space Agency sponsored project, are presented here to demonstrate the applicability of the proposed two stage approach, reporting on the savings in power consumption when an Nth-band all-pass-based recursive filter having an infinite impulse response is used as the digital prototype filter.

Preclinical tests in animal models are key steps in early drug development. Consequently, the International Society of Nephrology held a consensus meeting that connected experts in the global kidney community in order to provide guidance on optimal management of translational animal studies for the development of new drugs to treat kidney disease, entitled “TRANSFORM; TRAnslational Nephrology Science FOR new Medications.” The meeting covered various themes, including the following: (i) selection of disease model; (ii) pharmacokinetics; (iii) interventions in late preclinical models; (iv) choice of animal; (v) statistical power; (vi) organoids and organ-on-a-chip models; and (vii) reporting of results. This guidance is the first to be provided on the optimal conduct of translational animal studies for the development of new drugs to treat kidney disease. These recommendations are designed to accelerate development of new drugs for efficacious treatment of kidney diseases, and to improve the prognosis and quality of life of patients with a variety of kidney diseases.

Abstract:This article discusses the benefits to be derived, in Romantic studies, from an intersection of the methods and approaches of geo-criticism and eco-criticism. It stresses the importance of considering the geographical specificities of Romantic-era engagements with ecosystems, and, more precisely, how such engagements were bound up with geo-political and geo-cultural concerns. In particular, the article proposes methodological intersections of geo- and eco-criticism as a means of shedding new light on how Romantic-period representations of Italy problematize the interconnections between the country's highly diverse natural environments and its cultural, political, and economic dimensions.

Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.

New deterministic procedures for the design of linear aperiodic arrays are described, which permit exploiting, in a combined way, both the positions and the excitation amplitudes of the array elements obtaining a pattern, which optimally fits, in terms of a weighted L2 norm, the pattern of a reference linear continuous aperture. The first numerical procedure is based on alternating optimization of positions and amplitudes by means of closed-form convex projectors. Sufficient conditions for the solution to be optimal are established. A second numerical procedure is based on a domino-like sequential determination of the unknowns, which can be iterated to convergence. In addition, analytical asymptotic expressions for the optimal interelement spacing and amplitude are derived by means of variational techniques. The optimal asymptotic interelement spacing is demonstrated to be proportional to the reference tapering to the power ( $- \frac {2}{3}$ ), while the optimal asymptotic array amplitude is proportional to the reference tapering to the power ( $\frac {1}{3}$ ). For aperiodic arrays with equiamplitude excitation, it is proven that the optimal interelement spacing is proportional to the reference tapering to the power (−1). Based on these asymptotic dependencies, closed-form analytical solutions are obtained for amplitudes and positions of the elements. Several numerical results confirm the effectiveness and accuracy of the new procedures.

This article describes the development of a novel Ka-band array fed reflector antenna based on a passive multifeed-per-beam (MFPB) beamforming network (BFN) to realize multiple shaped beams for broadband satellite communications applications. The feeding array is organized in non-regular overlapped sub-arrays (OSAs) in order to generate contiguous shaped beams in two polarizations with a single reflector. The main novelty is the generation of the non-regular multibeam coverage with differently shaped beams which equalizes the traffic demand per beam as generated by a non-uniform distribution of users over the satellite coverage. The entire feeding array is organized in two interleaved and partially overlapped groups of sub-arrays, one per polarization, to better satisfy the beam overlap requirements and isolation between co-polarized beams. A complex BFN has been developed as a monolithic component through a 3-D additive manufacturing (AM) technique. The test campaign demonstrated the suitability of the design approach and the accuracy of the selected manufacturing technique for the Ka-band frequencies, with a good correlation between measured and simulated results.

The release of engineered nanomaterials (ENMs) during manufacturing, use and disposal of nano-enabled products (NEPs) is a potential route of environmental nanopollution. To date, there is limited knowledge on the ecological impact of ENMs incorporated in NEP matrices and how they compare to pristine nanoparticles. Here, we examined the fate and effect of silver nanowires (AgNWs) embedded in a cellulose matrix for the production of printed paper electronics (PPE) (nano)technologies. The fate and impact of fragmented AgNWs-PPE was monitored for 21 days in freshwater mesocosms mimicking a pond ecosystem. The Ag release and AgNWs-PPE behavior in water was further characterized in abiotic batch incubations. Qualitative and quantitative analyses were carried out to estimate the Ag partitioning between the environmental compartments and the aging of AgNWs-PPE as well as bioaccumulation and behavioral responses in biota. In contaminated pond mesocosms, the NEP cellulose/polyvinylidene chloride matrix resulted in rapid settling of the Ag on the sediments and prevented Ag release into the water column. The highest aqueous concentration measured corresponded to less than 0.5% of the total Ag introduced. The AgNWs-PPE fragments accumulated at the water sediment interface, where they were rapidly (bio)degraded and became bioavailable for benthic organisms. Aquatic snails accumulated a significant fraction of the Ag (1.4 ± 0.5%) and displayed enhanced burrowing behavior in comparison to controls. In batch experiments, alteration of the ENM morphology was evident at the NEP surface. Here, the colocalization of Ag and S clusters suggests aging viasulfidation, similar to other pristine Ag ENMs. However, the cellulose matrix prevented weathering of the AgNWs within the NEP, which presented a near-pristine state even after 21 days of incubation. Overall, these results indicate that the fate and impact of Ag embedded in the AgNWs-PPE were driven by the cellulose matrix. In particular, given the specific properties and behavior of paper-based (nano)products, these may constitute a unique category when evaluating NEP environmental impact. The data gathered in this study can help in defining the environmental fate of such materials and provide useful information to address future studies focused on ENM environmental fate and risk assessment in a life-cycle perspective.

The use of multiport power amplifiers for satellite transponders is described. These amplifiers have enabled higher edge of coverage gains and more efficient use of the frequency spectrum.

Children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) often require multiple courses of rituximab. However, long-term effects from repeated treatments remain unknown. In this international, multicenter study of 346 children receiving 1149 courses of rituximab, the risk of relapse decreased and relapse-free survival significantly improved with repeated treatments. Important side effects, including hypogammaglobulinemia, neutropenia, and infections, were mostly mild, but significant adverse events could occur. The incidence of side effects did not increase with more treatment courses nor a higher cumulative dose of rituximab. These findings suggest that repeating rituximab therapy is an effective and reasonably safe approach for most children with FRSDNS.

Purpose: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) frequently exhibit Non-Suicidal Self-Injury (NSSI), yet their co-occurrence is still unclear. To address this issue, the aim of this study was to elucidate the role of impairments in interoception in explaining the NSSI phenomenon in AN and BN, providing an explanatory model that considers distal (insecure attachment/IA and traumatic childhood experiences/TCEs) and proximal (dissociation and emotional dysregulation) risk factors for NSSI. Method: 130 patients with AN and BN were enrolled and administered self-report questionnaires to assess the intensity of NSSI behaviors, interoceptive deficits, IA, TCEs, emotional dysregulation and dissociative symptoms. Results: Results from structural equation modeling revealed that impairments in interoception acted as crucial mediators between early negative relational experiences and factors that contribute to NSSI in AN and BN, particularly emotional dysregulation and dissociation. Precisely, both aspects of IA (anxiety and avoidance) and various forms of TCEs significantly exacerbated interoceptive deficits, which in turn are associated to the emergence of NSSI behaviors through the increase in levels of dissociation and emotional dysregulation. Conclusions: The proposed model provided a novel explanation of the occurrence of NSSIs in patients with AN and BN by accounting for the significance of interoception.

The most recent developments in beam-forming network (BFN) technology for satellite multiple beams and reconfigurable antennas in Europe are discussed. The European space industry, which has been at the forefront of development of these systems, needs to expand development and production capability to attain independence and competitiveness.

Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103+cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3−/− mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt+T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.

Exhaustion of T cells occurs in response to long-term exposure to self and foreign antigens. It limits T cell capacity to proliferate and produce cytokines, leading to an impaired ability to clear chronic infections or eradicate tumors. T-cell exhaustion is associated with a specific transcriptional, epigenetic, and metabolic program and characteristic cell surface markers’ expression. Recent studies have begun to elucidate the role of T-cell exhaustion in transplant. Higher levels of exhausted T cells have been associated with better graft function in kidney transplant recipients. In contrast, reinvigorating exhausted T cells by immune checkpoint blockade therapies, while promoting tumor clearance, increases the risk of acute rejection. Lymphocyte depletion and high alloantigen load have been identified as major drivers of T-cell exhaustion. This could account, at least in part, for the reduced rates of acute rejection in organ transplant recipients induced with thymoglobulin and for the pro-tolerogenic effects of a large organ such as the liver. Among the drugs that are widely used for maintenance immunosuppression, calcineurin inhibitors have a contrasting inhibitory effect on exhaustion of T cells, while the influence of mTOR inhibitors is still unclear. Harnessing or encouraging the natural processes of exhaustion may provide a novel strategy to promote graft survival and transplantation tolerance.

Agile maneuvering and precise pointing control require special attention for spacecraft equipped with large flexible appendages. A joint academia-industry research involving Sapienza University of Rome, Thales Alenia Space in France and the European Space Agency (ESA), investigates the use of innovative solutions to counteract the deterioration in pointing accuracy stemming from interactions between a rigid bus and the flexible structures during operations. Specifically, this paper aims at presenting the design of an attitude/vibration control architecture in a μ-synthesis framework. The architecture consists of an attitude control system combined with a distributed network of actuators/sensors at structural level for active vibration control purposes. A spacecraft equipped with an interferometric Ka-band SAR payload and two solar arrays is considered as a useful and challenging benchmark problem to assess the proposed methodology. The numerical simulations, carried out via both a linearized setting and a nonlinear simulator, have proved the effectiveness of the robust collocated control in comparison with a baseline PID controller.

Purpose: Anorexia nervosa (AN) is characterized by a diminished capacity in perceiving the physiological correlates of interoceptive sensations, namely bodily self-consciousness. Given the neural division of self-processing into interoceptive-, exteroceptive- and mental-self, we hypothesize neural deficits in the interoceptive-processing regions in AN. Methods: To prove this, we reviewed resting state (rs), task and rest-task studies in AN literature. Results: Neuronal data demonstrate the following in AN: (i) decreased rs-functional connectivity (rsFC) of subcortical–cortical midline structures (SCMS); (ii) reduced rsFC between medial (default-mode network/DMN and salience network/SN) and lateral (executive-control network/ECN) cortical regions; (iii) decreased rsFC in mainly the regions of the interoceptive-self; (iv) altered activity with overall increased activity in response to sensory/body image stimuli, especially in the regions of the interoceptive-self; (v) lack of a clear task-related distinction between own’s and others’ body image. Conclusion: These data may indicate that rs-hypoconnectivity between SCMS, as neural correlate of a reduced intero-exteroceptive integration resulting in self-objectification, might be linked to overall increased activity in interoceptive regions during sensory/body image stimuli in AN, engendering an “anxious bodily self.” Level of evidence: I: Systematic review.

This study addressed the impact of nanomaterials on anaerobic digestion and biogas production (methanogenesis pathways) when contaminating aerobic sludge is generated during wastewater treatment. Our experimental system was based on bioreactor operational parameters aligned with the operating conditions used in wastewater treatment plants (WWTP), a contamination scenario considering the treatment of nano-enabled products at the last stages of their life cycle, and nanomaterial concentrations close to those predicted in WWTP. The physico-chemical, microbiological and chemical engineering proxies studied all concluded that combusted nanoCeO2-enabled fuel additives transiently increased EPS production and specific hydrolytic enzymatic activities without altering the aerobic sludge microbial community structure nor the C, P, N removal capacity (spiked concentrations of 130 μg L−1during aerobic sludge production). However, the presence in the aerobic sludge biosolids of 99.9% of the total CeO2injected (without any change in speciation) altered the production, structure, and activity of the anaerobic sludge during digestion (impacting the EPS, ATP, lipase and α-glucosidase activities). Interestingly, these modifications of the anaerobic sludge activity shaped the methanogenesis pathways from acetoclastic to hydrogenotrophic and enhanced the biogas production with a significant increase in generated H2. In the context of developing a sustainable energy supply, we observed a continuous improvement of the biogas production in the contaminated bioreactor, which could increase the energy recovery potential of WWTPs.

Clinical Trial registry name and registration number:Zeus study, NCT02403115

A currently relevant topic is the development of on-orbit servicing missions designed to repair, refuel or deorbit non-co-operative spacecraft. For this purpose, it is possible to use space robotic systems composed of a main platform and one or more robotic arms. In this paper, the capacity of a dual-arm robotic system to manipulate and to deorbit a generic target will be analyzed. For this purpose, a mixed Kane–Newton multi-body model will be implemented; this model will allow to switch automatically from an open-chain configuration (target captured via a single robotic arm) to a closed-chain configuration (target captured via both robotic arms) and vice versa. The flexibility of the joints of the system and the flexibility of the components of the robotic arms will be considered in the model. The system will be properly sized to operate the deorbiting of the target. Under the hypothesis of planar motion, numerical results will be presented to validate the model and to demonstrate the correct sizing of the system.

Background: Surgical-site infections (SSIs) represent the most common complications after colorectal surgery (CS). Role of preoperative administration of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP), alone or in combination, in the prevention of SSIs after CS is debated. Aim of this study was to assess the effect of the introduction of an Implemented Infection Prevention Bundle (IIPB) in preventing SSIs in CS. Methods: A group of 251 patients (Group 1) who underwent CS receiving only preoperative intravenous antibiotic prophylaxis (IAP) was compared to a Group of 107 patients (Group 2) who also received the IIPB. The IIPB consisted of the combination of oral administrations of three doses of Rifaximin 400 mg and MBP the day before surgery and in the administration of a cleansing enema the day of the surgical procedure. Results: At the univariate analysis, Group 2 showed significant lower rates of wound infection (WI) (2.8% vs. 9.9%; p= 0.021) and anastomotic leakage (AL) (2.8% vs. 14.7%; p= 0.001) with shorter hospital stay (5 vs. 6 days; p< 0.0001). The probability of postoperative AL was lower in Group 2; patients in this Group resulted protected from AL; a statistically significant Odds ratio of 0.16 (CI 0.05–0.55 p= 0.0034) was found. In diabetic patients, that were at higher risk of WI (OR 3.53, CI 1.49–8.35 p= 0.002), despite having any impact on anastomotic dehiscence, the use of IIPB significantly reduced the rate of WI (0% vs 28.1%; p= 0.01). Conclusion: The use of an IIPB significantly reduces rates of SSIs and post-operative hospital stay after CS.

The crop rotation system in organic farming is a determinant factor to accumulate and preserve soil organic matter (SOM), and in depth knowledge on its effects is still lacking. Tillage intensity in particular is crucial to maintain soil aggregates and protect SOM from degradation. The evolution of SOM was tested in two adjacent fields under two different rotation cropping systems (low-intensity tillage and high-intensity tillage), and the effect of a further cultivation of legume in both fields was evaluated using 13carbon (C)-nuclear magnetic resonance (NMR) and elemental analysis of samples isolated through combined aggregate size and density fractionation. The two adjacent fields had been managed using the following organic farming methods for 13 seasons since 1998: i) alfalfa-based, with nitrogen (N) enrichment and low-frequency tillage with alfalfa (Medicago sativa) (9 seasons), winter wheat (Triticum durum) (3 seasons), and broad bean (Vicia faba) (1 season) and ii) cereal-based, with N depletion and annual tillage with barley (Hordeum vulgare) (7 seasons), sunflower (Helianthus annuus) (2 seasons), broad bean (Vicia faba) (3 seasons), and bare fallow (1 season). Soil sampling was carried out at the end of the 13-year rotation (T0, November 2011) and after winter wheat and chickpea cultivation in both fields over two subsequent years (T1, July 2013). Bulk organic C was significantly higher in the alfalfa-based system than in the cereal-based system at both T0 and T1, with SOM occluded in soil aggregates and associated with mineral particles. In terms of the macroaggregates heavy fraction at T0, the alfalfa-based field contained twice the organic C of that in the cereal-based field, as well as three times the organic C in the occluded particulate organic matter (POM). The occluded POM (oPOM) had a lower aryl/O-alkyl C ratio in the alfalfa-based system than in the cereal-based system, suggesting that oPOM undergoes a lower degree of decomposition during low-intensity management. The aryl/O-alkyl C ratios of the macro- and microaggregate oPOM decreased from T0 to T1 in the cereal-based system, suggesting increased protection of these fractions by soil aggregates. Thus, including legumes in crop rotation appears to positively affect the accumulation of SOM associated with mineral particles and within soil aggregates.

Background: Infection with human papillomavirus (HPV) type 16 (HPV16) is a major cause of high-grade cervical intraepithelial neoplasia (CIN). Experiments were planned to evaluate the role of cell-mediated immunity (e.g., lymphocyte proliferation) against HPV in the natural history of HPV-associated neoplasia and to identify antigenic sequences of the HPV16 proteins E6 and E7 against which an immune response may confer protection. Methods: Forty-nine women with abnormal cervical cytology and biopsy-confirmed CIN were followed through one or more clinic visits. Lymphoproliferative responses of peripheral blood mononuclear cells to HPV16 E6 and E7 peptides were assessed in long-term (3-week) cultures. HPV DNA was detected in cervicovaginal lavage by means of polymerase chain reaction and Southern blotting. Disease status was determined by cervical cytologic examination and colposcopy. Reported P values are two-sided. Results: Subjects with positive lymphoproliferative responses to E6 and/or E7 peptides were more likely to be HPV negative at the same clinic visit than were nonresponders (P = .039). Subjects who were negative for HPV and those with a low viral load were more likely to be responders than were those with a high viral load (P for trend = .037). Responses to N-terminal E6 peptide 369 were associated with absence of HPV infection at the same clinic visit (P = .015). Subjects with positive responses to E6 or E7 peptides at one clinic visit were 4.4 times more likely to be HPV negative at the next visit than were nonresponders (P = .142). Responses to E6 peptide 369 and/or E7 C-terminal peptide 109 were associated with an absence of HPV infection (P = .02 for both) and an absence of CIN (P = .04 and .02, respectively) at the next visit. Conclusions: Lymphoproliferative responses to specific HPV16 E6 and E7 peptides appear to be associated with the clearance of HPV infection and the regression of CIN. [J Natl Cancer Inst] 1997;89:1285-93]

Background: Tumors acquire nutrients that are essential for continued growth and an avenue for dissemination to the rest of the body by inducing angiogenesis (i.e., the formation of new blood vessels). Preliminary studies involving a number of different kinds of cancer have indicated that an assessment of tumor angiogenesis may be useful in predicting disease outcome. Purpose: In a prospective study, we evaluated the relationship between tumor angiogenesis and survival for 407 patients with non-small-cell lung carcinoma who were treated with potentially curative surgery. Methods: The study population consisted of 360 male and 47 female patients who underwent surgery consecutively at the Department of Surgery, University of Pisa, Italy, from March 1991 through December 1994. Follow-up lasted through February 1996, with a median follow-up for living patients of 29 months (range, 15-60 months). An anti-CD34 monocional antibody, which is specific for endothelial cells, and standard immunohistochemical techniques were used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel counts; the counts for single, high-power microscopic fields (magnification x250) in the three most intense areas of blood vessel growth for each sample were averaged. The median microvessel count in this series was 20, and the counts were categorized as follows: 1) low versus high ([is equal to or less than] 20 versus [is greater than] 20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31-40, and [is equal to or greater than] 41 microvessels). Disease-free and overall survival during follow-up were assessed. Kaplan-Meier survival curves were modeled in a univariate analysis of patient and tumor characteristics; the Cox proportional hazards model was used in multivariate analysis. Reported P values are two-sided. Results and Conclusions: In the univariate analysis, patients with larger tumors (P for trend [is less than] .00001), a more advanced tumor stage (P for trend [is less than] .00001), a greater degree of regional lymph node involvement (P for trend [is less than] .00001), or more vascularized tumors (high versus low microvessel count, P [is less than] .00001) experienced significantly reduced overall survival. When microvessel counts were analyzed in five categories, a highly significant trend (P [is less than] .00001) toward worse prognosis was observed with increasing tumor vascularity. In multivariate analysis, tumor microvessel count (P [is less than] .00001), tumor size (P = .0006), and regional lymph node status (P [is less than] .00001) retained independent prognostic value with respect to overall survival; among these variables, tumor microvessel count, considered as a continuous variable, was the most important, with a relative hazard of death of 8.38 (95% confidence interval = 4.19-16.78) associated with the highest microvessel counts. Implications: An evaluation of tumor angiogenesis may be useful in the postsurgical staging of patients with non-small-cell lung carcinoma and in identifying subsets of patients who may benefit from different postsurgical treatments.

Study objective: To determine the effect of elective thoracic surgery on energy metabolism and gas exchange and to evaluate whether the 30° sitting position would affect these variables. Design: Prospective, [...]

Cell proliferation of 40 peripheral, node-negative non-small cell lung cancers (NSCLC) treated with surgery alone was investigated by immunohistochemical analysis with the monoclonal antibody (MoAb) PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. Results were correlated with DNA ploidy and S-phase fraction (SPF) analyzed by DNA flow cytometric study. Mitotic count (MC) was analyzed by light microscopic study and histopathologic features. PCNA immunoreactivity was seen in all samples and confined to the nuclei of cancer, but not to the surrounding, tumor-negative cells; its frequency ranged from 0-70% (median, 15%), and tumors expressed either a low (0-25%, n = 25) or intermediate (26-75%, n = 15) proliferative activity. There was no relationship between PCNA immunoreactivity and tumor stage or among size, histologic type, and mitotic count (MC). Tumors with intratumoral blood vessel invasion (BVI) showed a significantly higher (P < 0.005) PCNA immunoreactivity than BVI-negative tumors. PCNA scores were significantly higher (P < 0.005) in DNA aneuploid (n = 22) than in DNA diploid (n = 18) tumors and correlated significantly with the SPF of DNA aneuploid tumors (r = 0.002, P = 0.9). Intermediate proliferating tumors had a significantly higher (P < 0.01) MC than their counterparts. In univariate analysis, significant predictors of survival were tumor classification (T1 versus T2), tumor size (less than or equal to 2.6 cm versus more than 2.6 cm), BVI (BVI-negative versus BVI-positive), MC (less than or equal to 8 versus more than 8), and PCNA immunoreactivity (low versus intermediate). DNA ploidy and SPF did not influence survival significantly. Only PCNA immunoreactivity retained its independent level of significance (P = 0.02) by multivariate analysis. It was concluded that PCNA immunostaining is a simple and clinically useful method for estimating cell proliferation in formalin-fixed, paraffin-embedded tissue of resected peripheral, node-negative NSCLC.

Invasive thymoma, a malignant tumor of the thymus gland, constitutes between 0.2 percent and 1.5 percent of all cancers. This cancer is generally treated with surgery followed by radiation to kill any cancer cells that may have spread beyond the boundary of the surgically removed tissues. However, invasive thymoma often penetrates tissues in the chest and neck which are not surgically removable; if these areas are also outside of the region receiving radiotherapy, then relapse is certain. It is natural, therefore, that attempts be made to improve the results of treatment for invasive thymoma by including chemotherapy. A study was conducted to evaluate neoadjuvant chemotherapy for invasive thymoma. Neoadjuvant chemotherapy is administered prior to surgery not only to destroy deposits of cancer cells which may not be surgically removed, but also to reduce the size of the primary tumor and render it more amenable to surgical resection. A total of seven patients with invasive thymoma were treated with cisplatin, epirubicin, and etoposide prior to surgery. Following surgery, radiotherapy was administered in doses ranging from 4,600 to 6,000 cGy. (A Gy, or Gray, is a dose of radiation equivalent to one joule of energy absorbed per kilogram of tissue; cGy is 1/100th of a Gray.) All seven patients achieved partial responses to the neoadjuvant chemotherapy. (A partial response is defined as a reduction in tumor mass of at least 50 percent.) In four cases, it was possible to completely remove the tumor mass. In only one case was it impossible to remove the complete tumor as determined by gross examination. In the remaining two cases, only microscopic examination revealed that the entire tumor had not been removed. One patient died of a brain tumor; he was found to be free of thymoma at autopsy. The remaining six patients are currently alive and free of disease at follow-up periods ranging from 8 to 24 months. It is estimated that the two-year survival for this group of patients may be around 80 percent. (Consumer Summary produced by Reliance Medical Information, Inc.)

The failure of treatment for lung cancer is generally indicated by the appearance of metastatic disease spread to distant parts of the body. One of the most common locations for metastatic lung cancer is the brain. Once lung cancer metastasis in the brain has been found, chances are good there are, in fact, more than one tumor; the identification of multiple tumors in the brain rules out surgery as a therapeutic option, leaving only the less-than-satisfactory whole-brain irradiation and chemotherapy. The best therapeutic choice is less certain, however, when only a single metastatic tumor is found in the brain. In about one-third of the cases, only one tumor develops in the brain, and some researchers believe that surgery remains an effective therapeutic approach in such cases. Other investigators remain skeptical. To help resolve this question, the cases of 37 patients with non-small cell lung cancer and a single brain metastasis were reviewed. Surgical removal of the primary tumor and the brain metastasis resulted in a five-year survival rate of 30 percent. The median survival was 27 months, which represents a range extending from three months to more than 10 years. Analysis of patient characteristics and treatments revealed that patients who received adjuvant chemotherapy as a part of their surgical treatment survived significantly longer than patients who did not. Three patients in the present study have survived over 10 years. These results strongly indicate that oncologists should review the assumption held by many that even a single brain metastasis heralds certain death. While in the past such patients were often treated only for the relief of symptoms, it is now clear that such patients should be treated with the intent to cure, and that long-term survival can be achieved by some patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Fault Detection and Isolation (FDI) techniques have captured extensive interest and attention in modern autonomous systems; in particular, they are of foremost importance in space applications, due to their scientific relevance, cost and current inability of doing on-orbit maintenance of space systems. In this scenario, FDI strategies are required to counteract possible failure events that, if not properly handled, can reduce system performance or compromise the realization of the mission objectives. In this paper, a model-based FDI strategy is implemented onboard a satellite equipped with a very large mesh reflector on which a distributed network of smart actuators/sensors is mounted to actively counteract undesired elastic vibrations. In particular, the detection and isolation of a possible piezo-actuator failure occurring in the Active Vibration Control (AVC) system of the antenna is addressed by a bank of Unknown Input Observers (UIOs). The design of the proposed UIOs is derived by solving a Linear Matrix Inequality (LMI) problem, which provides the conditions for their existence, and it is based on the linearized 3D state-space model of the controlled spacecraft, under the assumption that all the uncertainties, exogenous disturbances and measurement noises are neglected. Furthermore, pole assignment in the sense of D-stability is integrated in the standard formulation of the UIO to guarantee an adequate transient behaviour of the observers. Finally, an extensive Monte Carlo simulation campaign is conducted to assess the effectiveness of the proposed FDI architecture and its robustness against modelling uncertainties and measurement noise.

Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking [...]

Aim:This study aimed to characterize the clinical and pathologic presentation of ocular surface tumors (OSTs) and to more precisely differentiate the grades of ocular surface squamous neoplasia (OSSN) and benign lesions among Zambians. Methods:Two-hundred sixty-five Zambian patients presenting with ocular surface growths, suspicious for OSSN, were recruited between November 2017 and November 2019 to a cross-sectional study to investigate their lesions. Sociodemographic data were collected, HIV infection status and vision tests were performed, and lesions were measured and documented. Lesions >2 mm in diameter were excised and sent for pathology analysis. In addition to the biopsies, tears, blood, and buccal swabs were collected. CD4+ T-cell counts were measured by flow cytometry. Lesions were classified according to the WHO guidelines. χ2 and bivariate correlations were used to analyze variable associations and strengths with phi/Cramer’s V and correlation coefficients, respectively. Binary logistics was used to adjust for covariance. Results:In this study, 68.3% of the participants were found to be HIV positive. The most frequent diagnoses were invasive OSSN (45.3%), preinvasive OSSN (29.1%), and pterygium (22.6%). Invasive OSSN comprised keratinizing squamous cell carcinoma (SCC) (87.5%), basaloid SCC (3.3%), and spindle cell carcinoma (3.3%). Unusual carcinomas, not described previously, included hybrid SCC (5.0%) and acantholytic SCC (0.8%). Invasive OSSN had advanced tumor (T3/T4) staging (93.3%) at diagnosis. Lymphadenopathy was rare (2.3%), and metastasis was absent. Patients were mostly female (59.2%). Median age was 36 (interquartile ranges 33–41) years (ranges 18–81). Patients with invasive OSSN were more likely to present with pain (p= 0.007), redness (p= 0.034), excessive tearing (p= 0.0001), discharge (p= 0.011), bleeding (p= 0.007), reduced vision (p= 0.0001), fungating lesion (p= 0.001), and blindness (p= 0.005); location at temporal limbus (p= 0.0001), inferior limbus (p= 0.0001), or circumlimbal (p= 0.001); and extension to cornea (p= 0.006) and forniceal palpebral conjunctiva (p= 0.001). Invasive OSSN was associated with any smoking habit and alcohol consumption (p= 0.04 and 0.03, respectively). HIV positivity was strongly associated with OSSN (74.6% OSSN vs. 49.3% benign lesions; p= 0.0001; phi: 0.237 [p= 0.0001]). Conclusion:OSTs are very common in Zambia and are strongly associated with HIV coinfection. Patients with OSSN were more likely to be HIV positive than those with pterygia. Despite the commonality of OSTs in sub-Saharan Africa, these cancers have historically been poorly characterized.

Introduction: The aim of the current systematic review is to update the pooled survival outcome of patients with T2 glottic carcinoma treated with either laser surgery (CO2transoral laser microsurgery [CO2TOLMS]), radiotherapy (RT), or open partial laryngectomy (OPL).Methods: A systematic search was performed using the MEDLINE database, Scopus, and Google scholar. The inclusion criteria were studies of patients with T2N0 glottic tumor, treated with either primary CO2TOLMS, definitive curative RT, or primary OPL, and with reported oncological outcome at 5 years calculated with a Kaplan-Meier or Cox regression method.Results: The results of the current review show that local control (LC) is higher with OPL 94.4%, while there are no differences in LC at 5-year posttreatment for patients treated with RT, compared to those treated with CO2TOLMS (respectively, 75.6% and 75.4%). Primary treatment with OPL and CO2TOLMS results in higher laryngeal preservation than primary treatment with RT (respectively 95.8%, 86.9%, and 82.4%).Conclusion: First-line treatment with OPL and CO2TOLMS should be encouraged in selected T2 patients, because it results in higher laryngeal preservation and similar LC compared to primary treatment with RT. The involvement of the anterior commissure in the craniocaudal plane and T2b impaired vocal cord mobility have a poorer prognosis and LC compared to patients with T2a tumors for both CO2TOLMS and RT.

BackgroundQuick Sequential Organ Failure Assessment (qSOFA) score is a bedside prognostic tool for patients with suspected infection outside the intensive care unit (ICU), which is particularly useful when laboratory analyses are not readily available. However, its performance in potentially septic patients with community-acquired pneumonia (CAP) needs to be examined further, especially in relation to early outcomes affecting acute management.ObjectiveFirst, to compare the performance of qSOFA and CURB-65 in the prediction of mortality in the emergency department in patients presenting with CAP. Second, to study patients who required critical care support (CCS) and ICU admission.MethodsBetween January and December 2017, a 1-year retrospective observational study was carried out of adult (≥18 years old) patients presenting to the emergency department (ED) of our hospital (Rome, Italy) with CAP. The accuracy of qSOFA, qSOFA-65 and CURB-65 was compared in predicting mortality in the ED, CCS requirement and ICU admission. The concordance among scores ≥2 was then assessed for 30-day estimated mortality prediction.Results505 patients with CAP were enrolled. Median age was 71.0 years and mortality rate in the ED was 4.7%. The areas under the curve (AUCs) of qSOFA-65, CURB-65 and qSOFA in predicting mortality rate in the ED were 0.949 (95% CI 0.873 to 0.976), 0.923 (0.867 to 0.980) and 0.909 (0.847 to 0.971), respectively. The likelihood ratio of a patient having a qSOFA score ≥2 points was higher than for qSOFA-65 or CURB-65 (11 vs 7 vs 6.7). The AUCs of qSOFA, qSOFA-65 and CURB-65 in predicting CCS requirement were 0.862 (95% CI 0.802 to 0.923), 0.824 (0.758 to 0.890) and 0.821 (0.754 to 0.888), respectively. The AUCs of qSOFA-65, qSOFA and CURB-65 in predicting ICU admission were 0.593 (95% CI 0.511 to 0.676), 0.585 (0.503 to 0.667) and 0.570 (0.488 to 0.653), respectively. The concordance between qSOFA-65 and CURB-65 in 30-day estimated mortality prediction was 93%.ConclusionqSOFA is a valuable score for predicting mortality in the ED and for the prompt identification of patients with CAP requiring CCS. qSOFA-65 may further improve the performance of this useful score, showing also good concordance with CURB-65 in 30-day estimated mortality prediction.

The current Tumor Node Metastasis staging system (TNM) for gastric cancer classifies the extent of lymph node metastasis based upon the number of lymph nodes involved. Choi et al. have recently proposed a new anatomical classification based upon the regionality of the involved nodes. This new classification seems to have a better predictive prognostic value than the traditional one. We investigated the prognostic role of the new anatomical based classification, reviewing our institutional gastric cancer database.