Conclusions and Future Research Directions

In this book, we have discussed channel estimation for various situations in PLNC, including frequency flat fading environment, frequency selective fading environment, and time-selective fading environment. In each environment, we demonstrated how the channel estimation is different from the conventional point-to-point transmission as well as from the uni-directional relay network. The key idea is that the individual channel knowledge should be obtained at three nodes, i.e., the terminals and the relay, within one round of the data exchange. One may, of course, apply more complicated training process, say, training each channel link separately and share the information through feedback channels but such processing is not compatible with the overall structure of the data frame. Moreover, we developed channel estimation algorithms that fit the speciality of different environments, for example in frequency selective fading environment it is possible to remove the redundant estimates so that the overall training length could be reduced, while in time selective fading environment the individual BEM coefficient is estimated instead of the channel parameters

A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

Emergency and critical care services in Tanzania: a survey of ten hospitals.

While there is a need for good quality care for patients with serious reversible disease in all countries in the world, Emergency and Critical Care tends to be one of the weakest parts of health systems in low-income countries. We assessed the structure and availability of resources for Emergency and Critical Care in Tanzania in order to identify the priorities for improving care in this neglected specialty. Ten hospitals in four regions of Tanzania were assessed using a structured data collection tool. Quality was evaluated with standards developed from the literature and expert opinion. Important deficits were identified in infrastructure, routines and training. Only 30% of the hospitals had an emergency room for adult and paediatric patients. None of the seven district and regional hospitals had a triage area or intensive care unit for adults. Only 40% of the hospitals had formal systems for adult triage and in less than one third were critically ill patients seen by clinicians more than once daily. In 80% of the hospitals there were no staff trained in adult triage or critical care. In contrast, a majority of equipment and drugs necessary for emergency and critical care were available in the hospitals (median 90% and 100% respectively. The referral/private hospitals tended to have a greater overall availability of resources (median 89.7%) than district/regional hospitals (median 70.6). Many of the structures necessary for Emergency and Critical Care are lacking in hospitals in Tanzania. Particular weaknesses are infrastructure, routines and training, whereas the availability of drugs and equipment is generally good. Policies to improve hospital systems for the care of emergency and critically ill patients should be prioritised

Distinct Olfactory Cross-Modal Effects on the Human Motor System

BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications

Soil Microbial Responses to Elevated CO2 and O3 in a Nitrogen-Aggrading Agroecosystem

Climate change factors such as elevated atmospheric carbon dioxide (CO2) and ozone (O3) can exert significant impacts on soil microbes and the ecosystem level processes they mediate. However, the underlying mechanisms by which soil microbes respond to these environmental changes remain poorly understood. The prevailing hypothesis, which states that CO2- or O3-induced changes in carbon (C) availability dominate microbial responses, is primarily based on results from nitrogen (N)-limiting forests and grasslands. It remains largely unexplored how soil microbes respond to elevated CO2 and O3 in N-rich or N-aggrading systems, which severely hinders our ability to predict the long-term soil C dynamics in agroecosystems. Using a long-term field study conducted in a no-till wheat-soybean rotation system with open-top chambers, we showed that elevated CO2 but not O3 had a potent influence on soil microbes. Elevated CO2 (1.5×ambient) significantly increased, while O3 (1.4×ambient) reduced, aboveground (and presumably belowground) plant residue C and N inputs to soil. However, only elevated CO2 significantly affected soil microbial biomass, activities (namely heterotrophic respiration) and community composition. The enhancement of microbial biomass and activities by elevated CO2 largely occurred in the third and fourth years of the experiment and coincided with increased soil N availability, likely due to CO2-stimulation of symbiotic N2 fixation in soybean. Fungal biomass and the fungi∶bacteria ratio decreased under both ambient and elevated CO2 by the third year and also coincided with increased soil N availability; but they were significantly higher under elevated than ambient CO2. These results suggest that more attention should be directed towards assessing the impact of N availability on microbial activities and decomposition in projections of soil organic C balance in N-rich systems under future CO2 scenarios

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability