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People affected by bipolar disorders experience alternating states of depression with episodes of mania or hypomania. This mental can lead to a poor handling of daily routines, can worsen personal relationships, and often can be life-threatening. This preliminary study aims at investigating how the autonomic nervous system, in terms of electrodermal activity, responds to specific controlled emotional stimuli in bipolar patients. More specifically, we present here a method to deploy the analysis of ElectroDermal Activity (EDA) to discriminate clinical mood states. EDA was analyzed by using a deconvolution method to separate tonic from phasic components. The three subjects recruited and the experimental protocol used here is part of the European project PSYCHE. Preliminary results show that the bipolar mood states can be related to electrodermal tonic activity.

Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5 mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20 mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens.

An unanswered question in adult language learning or late bi and multilingualism is why individuals show marked differences in their ability to imitate foreign accents. While recent research acknowledges that more adults than previously assumed can still acquire a "native" foreign accent, very little is known about the neuro-cognitive correlates of this special ability. We investigated 140 German-speaking individuals displaying varying degrees of "mimicking" capacity, based on natural language text, sentence, and word imitations either in their second language English or in Hindi and Tamil, languages they had never been exposed to. The large subject pool was strictly controlled for previous language experience prior to magnetic resonance imaging. The late-onset (around 10 years) bilinguals showed significant individual differences as to how they employed their left-hemisphere speech areas: higher hemodynamic activation in a distinct fronto-parietal network accompanied low ability, while high ability paralleled enhanced gray matter volume in these areas concomitant with decreased hemodynamic responses. Finally and unexpectedly, males were found to be more talented foreign speech mimics.

Mechanisms of cortical reorganization underlying the enhancement of speech processing have been poorly investigated. In the present study, we addressed changes in functional and effective connectivity induced in subjects who learned to deliberately increase activation in the right inferior frontal gyrus (rIFG), and improved their ability to identify emotional intonations by using a real-time fMRI Brain-Computer Interface. At the beginning of their training process, we observed a massive connectivity of the rIFG to a widespread network of frontal and temporal areas, which decreased and lateralized to the right hemisphere with practice. Volitional control of activation strengthened connectivity of this brain region to the right prefrontal cortex, whereas training increased its connectivity to bilateral precentral gyri. These findings suggest that changes of connectivity in a functionally specific manner play an important role in the enhancement of speech processing. Also, these findings support previous accounts suggesting that motor circuits play a role in the comprehension of speech., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Neurofeedback of functional magnetic resonance imaging (fMRI) can be used to acquire selective control over activation in circumscribed brain areas, potentially inducing behavioral changes, depending on the functional role of the targeted cortical sites. In the present study, we used fMRI-neurofeedback to train subjects to enhance regional activation in the right inferior frontal gyrus (IFG) to influence speech processing and to modulate language-related performance. Seven subjects underwent real-time fMRI-neurofeedback training and succeeded in achieving voluntary regulation of their right Brodmann's area (BA) 45. To examine short-term behavioral impact, two linguistic tasks were carried out immediately before and after the training. A significant improvement of accuracy was observed for the identification of emotional prosodic intonations but not for syntactic processing. This evidence supports a role for the right IFG in the processing of emotional information and evaluation of affective salience. The present study confirms the efficacy of fMRI-biofeedback for noninvasive self-regulation of circumscribed brain activity., ((c) 2008 Wiley-Liss, Inc.)

Previous studies investigating the anterior cingulate cortex (ACC) have relied on a number of tasks which involved cognitive control and attentional demands. In this fMRI study, we tested the model that ACC functions as an attentional network in the processing of language. We employed a paradigm that requires the processing of concurrent linguistic information predicting that the cognitive costs imposed by competing trials would engender the activation of ACC. Subjects were confronted with sentences where the semantic content conflicted with the prosodic intonation (CONF condition) randomly interspaced with sentences which conveyed coherent discourse components (NOCONF condition). We observed the activation of the rostral ACC and the middle frontal gyrus when the NOCONF condition was subtracted from the CONF condition. Our findings provide evidence for the involvement of the rostral ACC in the processing of complex competing linguistic stimuli, supporting theories that claim its relevance as a part of the cortical attentional circuit. The processing of emotional prosody involved a bilateral network encompassing the superior and medial temporal cortices. This evidence confirms previous research investigating the neuronal network that supports the processing of emotional information.

Brain-computer interfaces based on functional magnetic resonance imaging (fMRI-BCI) allow volitional control of anatomically specific regions of the brain. Technological advancement in higher field MRI scanners, fast data acquisition sequences, preprocessing algorithms, and robust statistical analysis are anticipated to make fMRI-BCI more widely available and applicable. This noninvasive technique could potentially complement the traditional neuroscientific experimental methods by varying the activity of the neural substrates of a region of interest as an independent variable to study its effects on behavior. If the neurobiological basis of a disorder (e.g., chronic pain, motor diseases, psychopathy, social phobia, depression) is known in terms of abnormal activity in certain regions of the brain, fMRI-BCI can be targeted to modify activity in those regions with high specificity for treatment. In this paper, we review recent results of the application of fMRI-BCI to neuroscientific research and psychophysiological treatment.

The epidermis of the skin and skin appendages, such as nails, hair and sebaceous glands, depend on a balance of cell proliferation and terminal differentiation in order to fulfill their functions at the interface of the body and the environment. The differentiation of epithelial cells of the skin, commonly referred to as keratinocytes, involves major remodeling processes that generate metabolically inactive cell remnants serving as building blocks of the epidermal stratum corneum, nail plates and hair shafts. Only sebaceous gland differentiation results in cell disintegration and holocrine secretion. A series of studies performed in the past decade have revealed that the lysosome-dependent intracellular degradation mechanism of autophagy is active during keratinocyte differentiation, and the blockade of autophagy significantly alters the properties of the differentiation products. Here, we present a model for the autophagy-mediated degradation of organelles and cytosolic proteins as an important contributor to cellular remodeling in keratinocyte differentiation. The roles of autophagy are discussed in comparison to alternative intracellular degradation mechanisms and in the context of programmed cell death as an integral end point of epithelial differentiation. [ABSTRACT FROM AUTHOR]

The document is a collection of summaries of various research studies related to HIV prevention and treatment. The studies cover a range of topics, including the use of pre-exposure prophylaxis (PrEP), the development of HIV vaccines and antibodies, and the implementation of long-acting HIV prevention methods. The studies provide valuable insights into different strategies and interventions aimed at increasing HIV testing, prevention, and treatment outcomes. [Extracted from the article]

Lithium (Li), a leading cathode material in rechargeable Li-ion batteries, is vital to modern energy storage technology, establishing it as one of the most impactful and strategical elements. Given the surge in the electric car market, it is crucial to improve lithium recovery from its rich mineral deposits using the most effective extraction technique. In recent years, both industry and academia have shown significant interest in Li recovery from various Li-bearing minerals. Of these, only extraction from spodumene has established a reliable industrial production of Li salts. The current approaches for cracking of the naturally occurring, stable α-spodumene structure into a more open structure—β-spodumene—involve the so-called decrepitation process that takes place at extreme temperatures of ~1100 °C. This conversion is necessary, as β-spodumene is more susceptible to chemical attacks facilitating Li extraction. In the last several decades, many techniques have been demonstrated and patented to process hard-rock mineral spodumene. The objective of this review is to present a thorough analysis of significant findings and the enhancement of process flowsheets over time that can be useful for both research endeavors and industrial process improvements. The review focuses on the following techniques: acid methods, alkali methods, carbonate roasting/autoclaving methods, sulfuric acid roasting/autoclaving methods, chlorinating methods, and mechanochemical activation. Recently, microwaves (MWs), as an energy source, have been employed to transform α-spodumene into β-spodumene. Considering its energy-efficient and short-duration aspects, the review discusses the interaction mechanism of MWs with solids, MW-assisted decrepitation, and Li extraction efficiencies. Finally, the merits and/or disadvantages, challenges, and prospects of the processes are summarized. [ABSTRACT FROM AUTHOR]

Mutant selective drugs targeting the inactive, GDP-bound form of KRASG12C have been approved for use in lung cancer, but resistance develops rapidly. Here we use an inhibitor, (RMC-4998) that targets RASG12C in its active, GTP-bound form, to treat KRAS mutant lung cancer in various immune competent mouse models. RAS pathway reactivation after RMC-4998 treatment could be delayed using combined treatment with a SHP2 inhibitor, which not only impacts tumour cell RAS signalling but also remodels the tumour microenvironment to be less immunosuppressive. In an immune inflamed model, RAS and SHP2 inhibitors in combination drive durable responses by suppressing tumour relapse and inducing development of immune memory. In an immune excluded model, combined RAS and SHP2 inhibition sensitises tumours to immune checkpoint blockade, leading to efficient tumour immune rejection. These preclinical results demonstrate the potential of the combination of RAS(ON) G12C-selective inhibitors with SHP2 inhibitors to sensitize tumours to immune checkpoint blockade. GDP-bound form of KRASG12C inhibitors have been approved for the treatment of patients with advanced KRASG12C mutant non-small cell lung cancer (NSCLC), however resistance to these drugs is often observed. Here the authors report that combining a GTP-bound RAS G12C-selective inhibitor with SHP2 inhibition can sensitize lung tumours to immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

Simple Summary: CAR T cells are a type of immune cell that is genetically engineered to better recognize and attack cancer cells. Before this treatment can be used to treat humans, it undergoes testing in pre-clinical models. Most of these models use mice that do not have an immune system, which means that these models may not accurately recapitulate CAR T cell actions in humans. This review focuses on how using syngeneic mouse models that have a functional immune system can result in better pre-clinical assessment of CAR T cells. Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies. Unfortunately, this improvement has yet to be translated into the solid tumor field. Current immunodeficient models used in pre-clinical testing often overestimate the efficacy of CAR T cell therapy as they fail to recapitulate the immunosuppressive tumor microenvironment characteristic of solid tumors. As CAR T cell monotherapy is unlikely to be curative for many solid tumors, combination therapies must be investigated, for example, stromal remodeling agents and immunomodulators. The evaluation of these combination therapies requires a fully immunocompetent mouse model in order to recapitulate the interaction between the host's immune system and the CAR T cells. This review will discuss the need for improved immunocompetent murine models for the pre-clinical evaluation of CAR T cells, the current use of such models and future directions. [ABSTRACT FROM AUTHOR]

Lysosomes are acidic organelles involved in crucial intracellular functions, including the degradation of organelles and protein, membrane repair, phagocytosis, endocytosis, and nutrient sensing. Given these key roles of lysosomes, maintaining their homeostasis is essential for cell viability. Thus, to preserve lysosome integrity and functionality, cells have developed a complex intracellular system, called lysosome quality control (LQC). Several stressors may affect the integrity of lysosomes, causing Lysosomal membrane permeabilization (LMP), in which membrane rupture results in the leakage of luminal hydrolase enzymes into the cytosol. After sensing the damage, LQC either activates lysosome repair, or induces the degradation of the ruptured lysosomes through autophagy. In addition, LQC stimulates the de novo biogenesis of functional lysosomes and lysosome exocytosis. Alterations in LQC give rise to deleterious consequences for cellular homeostasis. Specifically, the persistence of impaired lysosomes or the malfunctioning of lysosomal processes leads to cellular toxicity and death, thereby contributing to the pathogenesis of different disorders, including neurodegenerative diseases (NDs). Recently, several pieces of evidence have underlined the importance of the role of lysosomes in NDs. In this review, we describe the elements of the LQC system, how they cooperate to maintain lysosome homeostasis, and their implication in the pathogenesis of different NDs. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body's immune system to specifically target and destroy malignant cells. This review explores the scope and impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapy, and therapeutic vaccines. Monoclonal antibodies, such as Rituximab and Trastuzumab, have revolutionized treatment paradigms for lymphoma and breast cancer by offering targeted interventions that reduce off-target effects. CAR-T cell therapy presents a potentially curative option for refractory hematologic malignancies, although challenges remain in effectively treating solid tumors. Checkpoint inhibitors have redefined the management of cancers like melanoma and lung cancer; however, managing immune-related adverse events and ensuring durable responses are critical areas of focus. Cytokine therapy continues to play a vital role in modulating the immune response, with advancements in cytokine engineering improving specificity and reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based vaccines, represent a frontier in personalized cancer treatment, aiming to generate robust, long-lasting immune responses against tumor-specific antigens. Despite these advancements, the field faces significant challenges, including immune resistance, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Future research should address these obstacles through emerging technologies, such as next-generation antibodies, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, and AI-driven drug discovery. By integrating these novel approaches, cancer immunotherapy holds the promise of offering more durable, less toxic, and highly personalized treatment options, ultimately improving patient outcomes and survival rates. [ABSTRACT FROM AUTHOR]

Research has primarily focused on female sex workers, leaving a large gap in our understanding of the factors affecting the welfare of male sex workers (MSWs). The purpose of this study was to review the body of research on how substance addiction affects MSWs' health and welfare. Using Google Scholar, PubMed, Science Direct, Cochrane Library, Medline, and CINAHL, a systematic search was carried out. Included was all the research on the effects of drug misuse on the health and happiness of sex workers. The methodology for conducting systematic reviews developed by the Joanna Briggs Institute was applied in this review. The research encompassed English-language papers authored between 2000 and 2024 to guarantee a thorough analysis of current patterns and breakthroughs in the domain, mirroring the current obstacles and progressions in tackling substance addiction among male sex workers. Exclusion criteria were developed to guarantee the relevance and rigor of the included research, whereas inclusion criteria were set based on demographics, exposure, and results. Nineteen studies that met the inclusion criteria were found during the review. This study revealed three main themes: factors contributing to substance abuse among male sex workers; the correlation between substance abuse and mental health among sex workers; and the correlation between substance abuse and the incidence of STIs, including HIV. This study highlights the urgent need for comprehensive, inclusive approaches to address the specific needs of MSWs, ultimately aiming to improve their quality of life and reduce health disparities. [ABSTRACT FROM AUTHOR]

A node of a Sturm–Liouville problem is an interior zero of an eigenfunction. The aim of this paper is to present a simple and new proof of the result on sharp bounds of the node for the Sturm–Liouville equation with the Dirichlet boundary condition when the L 1 norm of potentials is given. Based on the outer approximation method, we will reduce this infinite-dimensional optimization problem to the finite-dimensional optimization problem. [ABSTRACT FROM AUTHOR]

The red palm weevil (Rhynchophorus ferrugineus) is a highly destructive pest, causing severe damage to palm trees and significantly reducing their productivity. This paper aims to develop and analyze a mathematical model that captures the interactions between palm trees, Rhynchophorus ferrugineus, and entomopathogenic nematodes as a means of integrated control. We identify the equilibrium points of the system and perform a stability analysis to assess the system's behavior. Additionally, we design a linear quadratic regulator (LQR) to limit the spread of the red palm weevil within a locally linearized framework. The feedback control law, which is both straightforward and immediately implementable, is employed to avoid the need for complex cost calculations, thus simplifying the solution to the optimal control problem. Numerical simulations demonstrate that the proposed control strategy is effective in reducing the number of infected palm trees. The results indicate that increasing the population of entomopathogenic nematodes can significantly decrease the red palm weevil population, offering a promising approach to mitigating this pest's impact. [ABSTRACT FROM AUTHOR]

Competencies defined in practice standards and frameworks promote safe and effective healthcare by underpinning training curricula and service standards. The provision of mobility assistive products involves a range of professionals, each guided by various standards and frameworks that define various competencies. This environmental scan aimed to identify global resources containing professional competencies applicable to mobility assistive product provision and to compare them against a gold standard. Competencies for mobility assistive products were found in 14 resources of diverse types. While there were similarities between competency standards, such as service steps, there were also significant differences, such as minimum education levels and competency domains. This environmental scan highlights an opportunity for professionals providing mobility assistive products to collaborate and establish unified competencies. Standardizing these competencies could harmonize training, regulation, and service standards, thereby improving coordination and service quality. Additionally, this approach could serve as a model for developing standardized competencies for other assistive products, such as hearing and vision aids, enhancing outcomes across various assistive technology types. [ABSTRACT FROM AUTHOR]

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies are particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment of tumors affects CAR-T cells, limiting the treatment's effectiveness and safety. Therefore, enhancing CAR-T cell infiltration capacity and resolving the immunosuppressive responses within the tumor microenvironment could boost the anti-tumor effect. Specific strategies include structurally altering CAR-T cells combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring the tumor microenvironment and the status of CAR-T cells is beneficial in further investigating the viability of such strategies and advancing CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Introduction: Tryptophan metabolism is strongly associated with immunosuppression and may influence lung adenocarcinoma prognosis as well as tumor microenvironment alterations. Methods: Sequencing datasets were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Two different clusters were identified by consensus clustering, and prognostic models were established based on differentially expressed genes (DEGs) in the two clusters. We investigated differences in mutational landscapes, enrichment pathways, immune cell infiltration, and immunotherapy between high- and low-risk scoring groups. Single-cell sequencing data from Bischoff et al. were used to identify and quantify tryptophan metabolism, and model genes were comprehensively analyzed. Finally, PTTG1 was analyzed at the pan-cancer level by the pan-TCGA cohort. Results: Risk score was defined as an independent prognostic factor for lung adenocarcinoma and was effective in predicting immunotherapy response in patients with lung adenocarcinoma. PTTG1 is one of the key genes, and knockdown of PTTG1 in vitro decreases lung adenocarcinoma cell proliferation and migration and promotes apoptosis and down-regulation of tryptophan metabolism regulators in lung adenocarcinoma cells. Discussion: Our study revealed the pattern and molecular features of tryptophan metabolism in lung adenocarcinoma patients, established a model of tryptophan metabolism-associated lung adenocarcinoma prognosis, and explored the roles of PTTG1 in lung adenocarcinoma progression, EMT process, and tryptophan metabolism. [ABSTRACT FROM AUTHOR]

On the one hand, we investigate the existence and pathwise uniqueness of a nonnegative martingale solution to the stochastic evolution system of nonlinear advection-diffusion equations proposed by Klausmeier with Gaussian multiplicative noise. On the other hand, we present and verify a general stochastic version of the Schauder-Tychonoff fixed point theorem, as its application is an essential step for showing existence of the solution to the stochastic Klausmeier system. The analysis of the system is based both on variational and semigroup techniques. We also discuss additional regularity properties of the solution. [ABSTRACT FROM AUTHOR]

Lysosomes are the degradative endpoints of material delivered by endocytosis and autophagy and are therefore particularly prone to damage. Membrane permeabilization or full rupture of lysosomal or late endosomal compartments is highly deleterious because it threatens cellular homeostasis and can elicit cell death and inflammatory signaling. Cells have developed a complex response to endo-lysosomal damage that largely consists of three branches. Initially, a number of repair pathways are activated to restore the integrity of the lysosomal membrane. If repair fails or if damage is too extensive, lysosomes are isolated and degraded by a form of selective autophagy termed lysophagy. Meanwhile, an mTORC1-governed signaling cascade drives biogenesis and regeneration of new lysosomal components to reestablish the full lysosomal capacity of the cell. This damage response is vital to counteract the effects of various conditions, including neurodegeneration and infection, and can constitute a critical vulnerability in cancer cells. [ABSTRACT FROM AUTHOR]

Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. Lysosomal dysfunction plays a central role in the pathobiology of Parkinson's disease (PD). Gain-of-function mutations in Leucine-rich repeat kinase 2 (LRRK2) cause familial PD and genetic variations in its locus increase the risk of developing the sporadic form of the disease. We previously uncovered a process we term LYTL (LYsosomal Tubulation/sorting driven by LRRK2), wherein membrane-damaged lysosomes generate tubules sorted into mobile vesicles. Subsequently, these vesicles interact with healthy lysosomes. LYTL is orchestrated by LRRK2 kinase activity, via the recruitment and phosphorylation of a subset of RAB GTPases. Here, we summarize the current understanding of LYTL and its regulation, as well as the unknown aspects of this process. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cells have emerged as a ground-breaking therapy for the treatment of hematological malignancies due to their capacity for rapid tumor-specific killing and long-lasting tumor immunity. However, the same success has not been observed in patients with solid tumors. Largely, this is due to the additional challenges imposed by safe and uniform target selection, inefficient CAR T-cell access to sites of disease and the presence of a hostile immunosuppressive tumor microenvironment. Literature was reviewed on the PubMed database from the first description of a CAR by Kuwana, Kurosawa and colleagues in December 1987 through to the present day. This literature indicates that in order to tackle solid tumors, CAR T-cells can be further engineered with additional armoring strategies that facilitate trafficking to and infiltration of malignant lesions together with reversal of suppressive immune checkpoints that operate within solid tumor lesions. In this review, we describe a number of recent advances in CAR T-cell technology that set out to combat the problems imposed by solid tumors including tumor recruitment, infiltration, immunosuppression, metabolic compromise, and hypoxia. [ABSTRACT FROM AUTHOR]

Estimating cognitive workload levels is an emerging research topic in the cognitive neuroscience domain, as participants' performance is highly influenced by cognitive overload or underload results. Different physiological measures such as Electroencephalography (EEG), Functional Magnetic Resonance Imaging, Functional near-infrared spectroscopy, respiratory activity, and eye activity are efficiently used to estimate workload levels with the help of machine learning or deep learning techniques. Some reviews focus only on EEG-based workload estimation using machine learning classifiers or multimodal fusion of different physiological measures for workload estimation. However, a detailed analysis of all physiological measures for estimating cognitive workload levels still needs to be discovered. Thus, this survey highlights the in-depth analysis of all the physiological measures for assessing cognitive workload. This survey emphasizes the basics of cognitive workload, open-access datasets, the experimental paradigm of cognitive tasks, and different measures for estimating workload levels. Lastly, we emphasize the significant findings from this review and identify the open challenges. In addition, we also specify future scopes for researchers to overcome those challenges. [ABSTRACT FROM AUTHOR]

We show that the Dedekind-MacNeille completion of any poset (P , ≤) can be recovered by algebraic means from the ideal structure of the finitary incidence algebra FI(P) over a commutative unital indecomposable ring R. [ABSTRACT FROM AUTHOR]

Matroid theory has been developed to be a mature branch of mathematics and has extensive applications in combinatorial optimization, algorithm design and so on. On the other hand, quantum computing has attracted much attention and has been shown to surpass classical computing on solving some computational problems. Surprisingly, crossover studies of the two fields seem to be missing in the literature. This paper initiates the study of quantum algorithms for matroid property problems. It is shown that quadratic quantum speedup is possible for the calculation problem of finding the girth or the number of circuits (bases, flats, hyperplanes) of a matroid, and for the decision problem of deciding whether a matroid is uniform or Eulerian, by giving a uniform lower bound Ω ( ( n ⌊ n / 2 ⌋ ) ) on the query complexity of all these problems. On the other hand, for the uniform matroid decision problem, an asymptotically optimal quantum algorithm is proposed which achieves the lower bound, and for the girth problem, an almost optimal quantum algorithm is given with query complexity O (log n ( n ⌊ n / 2 ⌋ ) ) . In addition, for the paving matroid decision problem, a lower bound Ω ( ( n ⌊ n / 2 ⌋ ) / n ) on the query complexity is obtained, and an O ( ( n ⌊ n / 2 ⌋ ) ) quantum algorithm is presented. [ABSTRACT FROM AUTHOR]

Since the beginning of transplant activities in 1989, the Kidney Transplant Center at the Ospedali Riuniti Bergamo has based its clinical program on the most recent achievements of transplant medicine, in order to optimize the outcome of kidney grafts and improve the quality of life of kidney transplant recipients. Although the transplantation community attempts to keep up with increasing demand for transplantable organs, the supply continues to fall far short of the need. This observation prompted us to focus on the expansion of the available pool of deceased donor organs. In 1997, we established a dual kidney transplant program for donors older than 60 years based on a pretransplant histology protocol with a scoring system ranging from low-dose RATG and delayed CsA administration has been successfully adopted in this population of kidney transplant recipients in our routine clinic practice. In kidney transplantation, chronic deterioration of renal function and death with a functioning graft, mainly due to side effects of the medications, represents a major limitation for long-term success of many transplant programs. We recently documented that per-protocol biopsy more than one year after kidney transplantation is a safe procedure to guide change of conventional immunosuppressive regimens and to lower the risk of major drug-related side effects. In particular, substantial reduction of the CsA dose, leading to extremely low CsA trough level, has no major detrimental effect on renal function and histology during 3 years follow-up, while patients remain free of rejection episodes with concomitant steroid and azathioprine therapy. Novel induction therapies with Campath-1H or Simulect and low-RATG have also helped to minimize maintenance immunosuppression in most patients largely avoiding the use of corticosteroids, Monitoring a patient's exposure to immunosuppressive agents is a critical issue in a minimum of 0 (no renal lesions) to a maximum of 12 (marked changes in renal parenchyma). The assumptions of the proposed algorithm to guide acceptance of single suboptimal or dual marginal kidneys for transplantation were validated in a prospective pilot study involving centers in Europe and North America. Whether the encouraging short-term data translate into improved graft survival is currently a matter of investigation in a prospective, multicenter, matched-cohort trial. As kidneys from marginal donors have an increased risk of delayed graft function, we also studied strategies to manage and prevent this complication. A dual immunosuppressive regimen of basiliximab and transplantation. By pharmacokinetics studies, we documented that a fixed dose regimen of MMF--adopted in the majority of transplant units worldwide--might no longer be the best approach for the management of transplant patients, and MPA pharmacokinetic monitoring is advised. Similarly, we reported pharmacokinetic interaction of concomitant immunosuppression on blood levels of the new immunosuppressant sirolimus. We have a special multiorgan transplant program at our center for patients affected by rare diseases, such as the recurrent hemolytic uremic syndrome (HUS). Based on genotyping for complement factor H-1, membrane co-factor protein or factor I gene mutations, we are exploring the possibility of combining liver and renal transplant or performing renal transplant alone in patients with recurrent HUS who have end-stage renal disease. The achievements of our clinical center are the result of the continuous support by an intense clinical and basic research program. This has allowed us to create a unique model to address the major challenges of transplant medicine.

Aim: UraTape is a new sling for female stress urinary incontinence (SUI) inserted via a transobturator percutaneous approach. We report the safety, feasibility and short-term results of this new surgical procedure., Methods: UraTape (Porgès-Mentor) is a non-elastic polypropylene tape, with a silicone coated central part. The sling is placed tension-free under the mid-urethra and extended through the obturator foramen bypassing the posterior face of the ischiopubic ramus. From September 2002 to May 2003, 80 females affected by SUI associated with urethral hypermobility and without severe uro-genital prolapse (with cystocele 1st grade) received UraTape. Mean age was 56 (39-79) years. Sixty-two out of 80 had a positive Q tip test; 16/80 had recurrent incontinence after Burch or colpoplasty according to Kelly; 22/60 had mixed incontinence. Preoperative evaluations included: complete history and physical examination, urinalysis, urodynamic investigations, abdominal and pelvic ultrasound. Quality of life assessment was carried out pre- and postoperatively., Results: Mean operative time was 16 (11-36) minutes. No major intraoperative complications were observed. One bladder neck laceration occurred and was treated intraoperatively. No cystoscopy was performed. Mean hospital postoperative stay time was 1.1 (1-6) days. All patients were examined periodically at 7, 30 and 90 days from intervention (mean follow-up 4 months, 1-8). There was no urethral erosion. One vaginal erosion with inguinal abscess was diagnosed and treated without removing the sling. Two de novo urge incontinence was observed. The objective and subjective cure rates were 92% and 97%; 96% expressed good quality of life (satisfied/very satisfied)., Conclusion: This procedure is a safe, effective new technique for the treatment of female SUI. The easy technique, the short learning curve and the very high grade of satisfaction of the patients show that this approach is based upon effective anatomical and physiological criteria. Further follow-up is necessary in order to evaluate urodynamic changes and overall satisfaction.

In our study we evaluate postoperative complications and local recurrence in local advanced rectal cancer after preoperative chemoradiation plus surgery. We treated 24 patients, 15 males and 9 females; in all cases the cancer was at stage II or III. Down-staging was observed in 14 patients (58.3%), 2 patients (8.3%) had no residual disease. We performed 2 APR, 20 low anterior resections (10 of which laparoscopic) and 2 transanal local excisions. In postoperative period we observed 8 complications, 4 minor and 4 major ones, with an over-all morbidity of 33.3% and of 16.6% if considering major complications. At present no local recurrence was registered.

One of the most important results in geometric convexity is Hadwiger's characterization of quermassintergrals and intrinsic volumes. The importance lies in that Hadwiger's theorem provides straightforward proofs of numerous results in integral geometry such as the kinematic formulas [Santaló, L. A.: Integral Geometry and Geometric Probability, Addison-Wesley, 1976], the mean projection formulas for convex bodies [Schneider, R.: Convex Bodies: The Brunn–Minkowski Theory, Cambridge Univ. Press, 1993], and the characterization of totally invariant set functions of polynomial type [Chen, B. and Rota, G.-C.: Totally invariant set functions of polynomial type, Comm. Pure Appl. Math.47 (1994), 187–197]. For a long time the only known proof of Hadwiger's theorem was his original one [Hadwiger, H.: Vorlesungen über Inhalt, Oberfläche and Isoperimetrie, Springer, Berlin, 1957] (long and not available in English), until a new proof was obtained by Klain [Klain, D. A.: A short proof of Hadwiger's characterization theorem, Mathematika42 (1995), 329–339., Klain, D. A. and Rota, G.-C.: Introduction to Geometric Probability, Lezioni Lincee, Cambridge Univ. Press, 1997], using a result from spherical harmonics. The present paper provides a simplified and self-contained proof of Hadwiger's theorem. [ABSTRACT FROM AUTHOR]

The kidney transplant program at the Ospedali Riuniti of Bergamo, Italy was established in 1989. Since its inception, 367 patients have been transplanted, including 357 kidney transplants from cadaveric donors and 10 from living-related donors. Overall 8-year patient and graft survival rates were 94% and 77%, respectively. By 1995 our unit co-ordinated the activity of the Department of Immunology and Clinics of Organ Transplantation, Ospedali Riuniti--Mario Negri Institute for Pharmacological Research, Bergamo. The dual "marginal" kidney transplant program in the same recipient was launched in August 1997, as a part of an international cooperative network which established the "Double Kidney Transplant Group" (DKG). To date, 19 dual kidney transplants have been successfully performed in our center. Four combined heart-kidney transplants and 2 combined liver-kidney transplants have also been performed. During the past 4 years several studies involving conventional antirejection drugs were carried out, particularly focussing our attention on cyclosporine (CsA) through pharmacokinetic and pharmacodynamic approaches: 1) a simplified method to evaluate daily exposure to CsA has been set up; 2) the monitoring of calcineurin activity in whole blood samples was evaluated as a way to optimize CsA dosing. As for the new immunosuppressants, studies are ongoing with mycophenolate mofetil (MMF). We are co-ordinating a prospective multicenter randomized trial of steroid sparing in kidney transplant recipients given MMF or azathioprine as a part of their immunosuppression therapy (MY.S.S. study). This involves 9 Italian transplant centers and 2 European centers. Up to now 325 patients have been randomized. Moreover we have set up an HPLC method for measuring plasma mycophenolic acid (MPA), and examined the possibility of optimizing MMF dosing by drug pharmacokinetic monitoring. Further studies have been addressed to chronic allograft nephropathy. The nature and mediators of renal lesions in kidney transplant patients given CsA have been explored taking into account the gene expression of endothelin-1, RANTES and MCP-1 in graft specimens from patients who had evidence of CsA nephrotoxicity, chronic rejection, or no lesions at histological examination. The impact of percutaneous transluminal angioplasty and stenting of posttransplant renal artery stenosis on renal function recovery was also recently examined. From this study we conclude that the procedure is safe and effective to normalize the functional changes sustained by hemodynamically significant artery stenosis. Moreover, Doppler ultrasound scanning is an useful, reliable, non-invasive tool to monitor the renal function response to artery revascularization. Thanks to the long-lasting co-operation with the Negri Bergamo Laboratories, we had in the past and still have an active program in experimental animals to investigate strategies for transplant tolerance and transplant gene therapy, besides addressing some issues related to the immunological barrier of xenotransplantation.