Optimal Dynamic Procurement Policies for a Storable Commodity with L\'evy Prices and Convex Holding Costs

In this paper we study a continuous time stochastic inventory model for a commodity traded in the spot market and whose supply purchase is affected by price and demand uncertainty. A firm aims at meeting a random demand of the commodity at a random time by maximizing total expected profits. We model the firm's optimal procurement problem as a singular stochastic control problem in which controls are nondecreasing processes and represent the cumulative investment made by the firm in the spot market (a so-called stochastic "monotone follower problem"). We assume a general exponential L\'evy process for the commodity's spot price, rather than the commonly used geometric Brownian motion, and general convex holding costs. We obtain necessary and sufficient first order conditions for optimality and we provide the optimal procurement policy in terms of a "base inventory" process; that is, a minimal time-dependent desirable inventory level that the firm's manager must reach at any time. In particular, in the case of linear holding costs and exponentially distributed demand, we are also able to obtain the explicit analytic form of the optimal policy and a probabilistic representation of the optimal revenue. The paper is completed by some computer drawings of the optimal inventory when spot prices are given by a geometric Brownian motion and by an exponential jump-diffusion process. In the first case we also make a numerical comparison between the value function and the revenue associated to the classical static "newsvendor" strategy.Comment: 28 pages, 3 figures; improved presentation, added new results and section

Un percorso di trasformazione nel nuovo assetto detentivo/riabilitativo post OPG: esposizione di un caso

L’articolo illustra il lavoro psicologico-clinico effettuato all’interno della “Articolazione per la Tutela della Salute Mentale in Carcere”, nuovo contesto di cura ed assistenza nato alla luce dei radicali cambiamenti attivati dal processo di superamento degli Ospedali Psichiatrici Giudiziari (OPG) e che accoglie soggetti autori di reato affetti da patologia psichiatrica, garantendone un’osservazione costante ed interventi riabilitativi ad alta intensità terapeutica. Il caso presentato, attraverso la narrazione del percorso detentivo/riabilitativo di un soggetto, iniziato con la reclusione in regime ordinario, proseguito con l’assegnazione all’OPG e con il successivo approdo presso l’Articolazione SMC (Salute Mentale in Carcere), ed esitato nel trasferimento in un contesto comunitario, mira ad essere esemplificativo della valenza trasformativa di un approccio rivolto al paziente che, nella gestione della patologia psichiatrica, superi i limiti di un assetto prevalentemente custodialistico, spesso predominante nei pregressi contesti ad essa dedicati, e dia priorità alle finalità terapeutico-riabilitative

Polyfunctional Melan-A-specific tumor-reactive CD8+ T cells elicited by dacarbazine treatment before peptide-vaccination depends on AKT activation sustained by ICOS

The identification of activation pathways linked to anti-tumor T-cell polyfunctionality in long surviving patients is of great relevance in the new era of immunotherapy. We have recently reported that dacarbazine (DTIC) injected one day before peptide-vaccination plus IFN-α improves the anti-tumor lytic activity and enlarges the repertoire of Melan-A-specific T-cell clones, as compared with vaccination alone, impacting the overall survival of melanoma patients. To identify the mechanisms responsible for this improvement of the immune response, we have analyzed the endogenous and treatment-induced antigen-specific response in a panel of Melan-A-specific CD8+ T-cell clones in terms of differentiation phenotype, inhibitory receptor profile, polyfunctionality and AKT activation. Here we show that Melan-A specific CD8+ T cells isolated from patients treated with chemoimmunotherapy possess a late differentiated phenotype as defined by the absence of CD28 and CD27 co-stimulatory molecules and high levels of LAG-3, TIM-3 and PD-1 inhibitory receptors. Nevertheless they show higher proliferative potential and an improved anti-tumor polyfunctional effector profile in terms of co-production of TNF-α, IFN-γ and Granzyme-B compared with cells derived from patients treated with vaccination alone. Polyfunctionality is dependent on an active AKT signalling related to the engagement of the co-stimulatory molecule ICOS. We suggest that this phenotypic and functional signature is dictated by a fine-tuned balance between TCR triggering, AKT activation, co-stimulatory and inhibitory signals induced by chemoimmunotherapy and may be associated with anti-tumor T cells able to protect patients from tumor recurrence

La cittadinanza nei piccoli stati europei. Profili di diritto comparato e internazionale.

Il tema della cittadinanza rientra in diversi ambiti disciplinari rappresentati dal diritto internazionale nonché da quello costituzionale e comparato. Nella prima parte del presente studio si è fornito un quadro generale dei principi fondamentali dettati in materia analizzando i vari modi in cui le legislazioni nazionali regolano il settore. La seconda parte della ricerca è stata dedicata all’esame della disciplina della cittadinanza nei c.d. microstati europei. Si è scelto di limitare il campo della ricerca alla normativa sulla nazionalità prevista dagli Stati che hanno una superficie estremamente ridotta (inferiore a 500 kmq) e una densità demografica molto alta in proporzione alle dimensioni territoriali (ad esempio, Malta e Monaco)

Resveratrol Reverts Tolerance and Restores Susceptibility to Chlorhexidine and Benzalkonium in Gram-Negative Bacteria, Gram-Positive Bacteria and Yeasts

The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) biocide in Acinetobacter baumannii. In this study, a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts were analyzed for susceptibility to CHX and benzalkonium chloride (BZK) and found to be tolerant to one or both biocides. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) efflux pump inhibitor reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CHX and BZK in the majority of strains. RV reduced dose-dependently MIC and MBC of CHX and BZK biocides when used as single agents or in combination in all analyzed strains, but not CHX MIC and MBC in Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Stenotrophomonas maltophilia and Burkholderia spp. strains. In conclusion, RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms responsible for HAI. These results indicates that the combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens

Ladylift® non-ablative laser technology for the treatment of menopausal vestibulodynia and genitourinary syndrome

Introduction: Genitourinary syndrome of menopause (GSM) affects up to 48% of pre-menopause women and up to 90% of menopausal women. Many menopausal women with dyspareunia have significant vestibular tenderness due to oestrogen deficiency, which increases the density of sensory nerve fibres in the vulva and the vagina. For this reason, GSM is recognized as one of the causes of provoked vestibulodynia. Few therapies have proven to be effective for provoked vestibulodynia. Many studies have shown the efficacy of laser CO2 therapy, proving its cost-effectiveness and safety for vaginal health.Material and methods: In this article we tested a new non-ablative solid-state laser: Ladylift (R). The main difference between Ladylift (R) and other laser technologies is the use of a non-ablative laser wavelength of 1470 nm, without causing ablative thermal injury on the surface of the mucosa. We enrolled 18 post-menopausal women presenting to a private clinic with GSM symptoms and provoked vulvodynia.Results: The treatment protocol consists of 4 sessions of laser, 2 weeks apart, of the duration of 4 minutes. Benefits to menopause symptoms, reported with a numeric rating scale, and to epithelium trophism reported with the vaginal health index were apparent since the first session. Patients undergoing laser therapy have had evident benefit both from the point of view of pain and from that of vaginal health. Conclusions: All the women tolerated the therapy well without any adverse effects. However, the beneficial effect tended to gradually decrease over time, suggesting the need to perform more therapy sessions

CUIDADOS DE ENFERMAGEM A SOBREVIVENTES DE SEPSE APÓS A ALTA DA UTI

Sepsis is defined as an organ dysfunction caused by a dysregulated answer to an infection, and it is configured as a global health issue. Septic patients frequently require Intensive Care Unit (ICU) stay to obtain proper support to the affected functions. After discharge, post-sepsis effects added to ICU stay leave patient vulnerable to complications. Nursing care to survivors of sepsis after ICU discharge is not yet widely described in literature. Considering that context, a systematic review was proposed with the objective to synthesize evidence about nursing care provided to patients discharged from the ICU after an episode of sepsis. Searches were done on the following databases: Cochrane Library, Cinahl, Embase, Lilacs, PubMed and Scopus. All steps were performed by two independent reviewers. 1012 articles were identified, from which 6 were selected for meeting the eligibility criteria. The results of this review showed that survivors of sepsis present different levels of impairment after ICU discharge, including decreased physical, cognitive and psychic functionality. Nursing care provided to survivors of sepsis after discharge were poorly described and were mostly related to assistance in daily activities. It is observed that further studies are relevant to comprehend post-sepsis and post-ICU morbidity, as well as to define effective care programs for reduction of readmission and mortality.La sepsis se define como una disfunción orgánica causada por una respuesta no regulada del cuerpo a una infección, y se configura como un problema de salud global. Los pacientes sépticos a menudo requieren ingreso en la Unidad de Cuidados Intensivos (UCI) para obtener un apoyo adecuado para las funciones de los órganos afectados. Después del alta, los efectos de la sepsis añadidos a la estancia en la UCI dejan al paciente susceptible a complicaciones. El papel de enfermería de los sobrevivientes de sepsis después del alta de la UTI todavía está mal descrito en la literatura, en vista de este contexto, se propuso una revisión sistemática con el objetivo de sintetizar la evidencia sobre la atención de enfermería prestada a los pacientes que fueron dados de alta de la UTI después de un episodio de sepsis. Las búsquedas se realizaron en las siguientes bases de datos: Cochrane Library, Cinahl, Embase, Lilacs, PubMed y Scopus. Todos los pasos fueron realizados por dos revisores de forma independiente. Se identificaron un total de 1.012 artículos, de los cuales 6 cumplieron con los criterios de elegibilidad y fueron seleccionados. Los resultados de esta revisión mostraron que los supervivientes de sepsis tienen niveles variables de deterioro después del alta de la UCI, incluida la disminución de la funcionalidad física, cognitiva y psíquica. La atención de enfermería prestada a los supervivientes de sepsis después del alta fue mal descrita y se relacionó principalmente con la asistencia en las actividades diarias. A sepse é definida como uma disfunção orgânica causada por uma resposta desregulada do organismo a uma infecção, e configura-se como um problema de saúde global. Pacientes sépticos com frequência requerem internação em Unidade de Terapia Intensiva (UTI) para obter suporte adequado para as funções orgânicas afetadas. Após a alta, os efeitos da sepse somados à estadia na UTI deixam o paciente suscetível a complicações. A atuação da enfermagem a sobreviventes de sepse após a alta da UTI ainda é pouco descrita na literatura, diante deste contexto foi proposta uma revisão sistemática com o objetivo de sintetizar as evidências sobre os cuidados de enfermagem fornecidos a pacientes que tiveram alta da UTI após um episódio de sepse. As buscas ocorreram nas seguintes bases de dados: Cochrane Library, Cinahl, Embase, Lilacs, PubMed e Scopus. Todas as etapas foram realizadas por dois revisores de forma independente. Foram identificados 1.012 artigos, dos quais 6 atenderam aos critérios de elegibilidade e foram selecionados. Os resultados desta revisão mostraram que os sobreviventes de sepse apresentam diversos níveis de comprometimento após a alta da UTI, incluindo diminuição da funcionalidade física, cognitiva e psíquica. Os cuidados de enfermagem fornecidos aos sobreviventes de sepse após a alta foram pouco descritos e estiveram relacionados principalmente à assistência em atividades diárias. Nota-se a importância de mais estudos para compreender a morbidade pós-sepse e pós-UTI, bem como para definir programas de cuidado que sejam eficazes na redução de readmissões e mortalidade.A sepse é definida como uma disfunção orgânica causada por uma resposta desregulada do organismo a uma infecção, e configura-se como um problema de saúde global. Pacientes sépticos com frequência requerem internação em Unidade de Terapia Intensiva (UTI) para obter suporte adequado para as funções orgânicas afetadas. Após a alta, os efeitos da sepse somados à estadia na UTI deixam o paciente suscetível a complicações. A atuação da enfermagem a sobreviventes de sepse após a alta da UTI ainda é pouco descrita na literatura, diante deste contexto foi proposta uma revisão sistemática com o objetivo de sintetizar as evidências sobre os cuidados de enfermagem fornecidos a pacientes que tiveram alta da UTI após um episódio de sepse. As buscas ocorreram nas seguintes bases de dados: Cochrane Library, Cinahl, Embase, Lilacs, PubMed e Scopus. Todas as etapas foram realizadas por dois revisores de forma independente. Foram identificados 1.012 artigos, dos quais 6 atenderam aos critérios de elegibilidade e foram selecionados. Os resultados desta revisão mostraram que os sobreviventes de sepse apresentam diversos níveis de comprometimento após a alta da UTI, incluindo diminuição da funcionalidade física, cognitiva e psíquica. Os cuidados de enfermagem fornecidos aos sobreviventes de sepse após a alta foram pouco descritos e estiveram relacionados principalmente à assistência em atividades diárias. Nota-se a importância de mais estudos para compreender a morbidade pós-sepse e pós-UTI, bem como para definir programas de cuidado que sejam eficazes na redução de readmissões e mortalidade

Phylogenomics of Acinetobacter species and analysis of antimicrobial resistance genes

Introduction: Non-baumannii Acinetobacter species are increasingly isolated in the clinical setting and the environment. The aim of the present study was to analyze a genome database of 837 Acinetobacter spp. isolates, which included 798 non-baumannii Acinetobacter genomes, in order to define the concordance of classification and discriminatory power of 7-gene MLST, 53-gene MLST, and single-nucleotide polymorphism (SNPs) phylogenies. Methods: Phylogenies were performed on Pasteur Multilocus Sequence Typing (MLST) or ribosomal Multilocus Sequence Typing (rMLST) concatenated alleles, or SNPs extracted from core genome alignment. Results: The Pasteur MLST scheme was able to identify and genotype 72 species in the Acinetobacter genus, with classification results concordant with the ribosomal MLST scheme. The discriminatory power and genotyping reliability of the Pasteur MLST scheme were assessed in comparison to genome-wide SNP phylogeny on 535 non-baumannii Acinetobacter genomes assigned to Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter seifertii, and Acinetobacter lactucae (heterotypic synonym of Acinetobacter dijkshoorniae), which were the most clinically relevant non-baumannii species of the A. baumannii group. The Pasteur MLST and SNP phylogenies were congruent at Robinson-Fould and Matching cluster tests and grouped genomes into four and three clusters in A. pittii, respectively, and one each in A. seifertii. Furthermore, A. lactucae genomes were grouped into one cluster within A. pittii genomes. The SNP phylogeny of A. nosocomialis genomes showed a heterogeneous population and did not correspond to the Pasteur MLST phylogeny, which identified two recombinant clusters. The antimicrobial resistance genes belonging to at least three different antimicrobial classes were identified in 91 isolates assigned to 17 distinct species in the Acinetobacter genus. Moreover, the presence of a class D oxacillinase, which is a naturally occurring enzyme in several Acinetobacter species, was found in 503 isolates assigned to 35 Acinetobacter species. Conclusion: In conclusion, Pasteur MLST phylogeny of non-baumannii Acinetobacter isolates coupled with in silico detection of antimicrobial resistance makes it important to study the population structure and epidemiology of Acinetobacter spp. isolates

Non-Aβ-dependent factors associated with global cognitive and physical function in alzheimer's disease: a pilot multivariate analysis

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aβ-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO₂max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO₂max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO₂max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO₂max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746)

The Role of NGF and Its Receptor TrKA in Patients With Erectile Dysfunction

The aim of our study was to investigate the plasma NGF concentration and TrkA/p75NTR receptor expression on white blood cells (WBCs), in peripheral and corpus cavernosum blood isolated from patients with erectile dysfunction and metabolic syndrome (ED/MetS). This was a pilot case–control study. Inclusion criteria were as follows: men 18–65 years with ED and MetS and healthy subjects. The first sampling was performed at the level of the cubital vein (VC). Subsequently, 20 μg of intracavernous alprostadil was administered, and a second blood draw from the corpora cavernosa (CC) was performed once erection was achieved. Subsequently, the third blood sample was repeated at the level of the VC. We enrolled 8 cases with ED/MetS and 8 controls. There was no significant difference between the case and control group in terms of mean age (49.3 ± 5.9 and 53.13 ± 8.9, respectively). The case group had a lower IIEF score compared to the control group (14 ± 3.2 versus 27.3 ± 2.1; p < 0.05). Decreased NGF and TrKA expression on WBC and thiols were found in the plasma of ED/MetS patients compared to control. The study showed that patients with ED/MetS had a decrease in plasma NGF and thiol concentration, and they had a decrease in TrKA expression on WBCs