Mild cognitive impairment: historical development and summary of research

This review article broadly traces the historical development, diagnostic criteria, clinical and neuropathological characteristics, and treatment strategies related to mild cognitive impairment (MCI), The concept of MCI is considered in the context of other terms that have been developed to characterize the elderly with varying degrees of cognitive impairment Criteria based on clinical global scale ratings, cognitive test performance, and performance on other domains of functioning are discussed. Approaches employing clinical, neuropsychological, neuroimaging, biological, and molecular genetic methodology used in the validation of MCI are considered, including results from cross-sectional, longitudinal, and postmortem investigations. Results of recent drug treatment studies of MCI and related methodological issues are also addressed

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome

OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania

Equilibrium and nonequilibrium properties associated with the chiral phase transition at finite density in the Gross-Neveu Model

We study the dynamics of the chiral phase transition at finite density in the Gross-Neveu (GN) model in the leading order in large-N approximation. The phase structure of the GN model in this approximation has the property that there is a tricritical point at a fixed temperature and chemical potential separating regions where the chiral transition is first order from that where it is second order. We consider evolutions starting in local thermal and chemical equilibrium in the massless unbroken phase for conditions pertaining to traversing a first or second order phase transition. We assume boost invariant kinematics and determine the evolution of the order parameter $\sigma$, the energy density and pressure as well as the effective temperature, chemical potential and interpolating number densities as a function of the proper time $\tau$. We find that before the phase transition, the system behaves as if it were an ideal fluid in local thermal equilibrium with equation of state $p=\epsilon$. After the phase transition, the system quickly reaches its true broken symmetry vacuum value for the fermion mass and for the energy density. The single particle distribution functions for Fermions and anti-Fermions go far out of equilibrium as soon as the plasma traverses the chiral phase transition. We have also determined the spatial dependence of the "pion" Green's function $<\bar{\psi}(x) \gamma_5 \psi(x) \bar{\psi}(0) \gamma_5 \psi(0)>$ as a function of the proper time.Comment: 39 pages, 23 figure

Violent Deaths of Iraqi Civilians, 2003–2008: Analysis by Perpetrator, Weapon, Time, and Location

Madelyn Hsiao-Rei Hicks and colleagues provide a detailed analysis of Iraqi civilian violent deaths during 2003-2008 of the Iraq war and show that of 92,614 deaths, unknown perpetrators caused 74% of deaths, Coalition forces 12%, and Anti-Coalition forces 11%

Assessment in the service of learning: challenges and opportunities or Plus ça Change, Plus c’est la même Chose

This paper begins with a brief overview of literature indicating that, although there have been significant advances in the field’s capacity to conduct both formative and summative assessments over the past decades, those advances have not been matched by comparable impact. The bulk of the paper is devoted to a series of examples from the Mathematics Assessment Project that illustrate issues of methods, and the unrealized potential for advances

2017 update of the WSES guidelines for emergency repair of complicated abdominal wall hernias

Emergency repair of complicated abdominal wall hernias may be associated with worsen outcome and a significant rate of postoperative complications. There is no consensus on management of complicated abdominal hernias. The main matter of debate is about the use of mesh in case of intestinal resection and the type of mesh to be used. Wound infection is the most common complication encountered and represents an immense burden especially in the presence of a mesh. The recurrence rate is an important topic that influences the final outcome. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013 with the aim to define recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. In 2016, the guidelines have been revised and updated according to the most recent available literature.Peer reviewe

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients

WSES guidelines for emergency repair of complicated abdominal wall hernias

Peer reviewe

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival