A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living

The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities

Role of positron emission tomography (PET) in advanced stage non-small cell lung cancer patients treated with cisplatin-based doublets

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Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study.

Objective: According to experimental findings, oxycodone (OX) could have some advantages over morphine (MO) in clinical models of visceral pain. It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain. Methods: Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study. Patients were randomized to receive 30mg/d of sustained release oral MO or sustained release oral OX (20mg/d). Opioid doses were increased according to the clinical needs. Daily doses of opioids, pain and symptom intensity were recorded at admission (T0) and at weekly intervals for the subsequent 4 weeks (T1, T2, T3, and T4), with an extension at 8 weeks (T8). Opioid escalation index (OEI) as percentage (OEI %) and in mg (OEI mg) was calculated. Results: Nineteen and 20 patients in groups OX and MO, respectively, were followed for the entire period of study (T4). No differences between groups were found in age (P=0.400), Karnofsky (P=0.667), or escalation indexes at T4 and T8 (OEImg, P=0.945 and OEI %, P=0.295). No statistical differences in pain and symptoms intensity between the groups were observed. Conclusion: OX and MO provided similar analgesia and adverse effects with similar escalating doses in patients with pancreatic cancer pain, resembling observations reported in the general cancer pain population. The experimental hypothesis that OX would be superior to MO in the clinical model of pancreatic cancer pain was not confirmed. © 2010 by Lippincott Williams & Wilkins

A Probabilistic Assessment of NASA Ultra-Efficient Engine Technologies for a Large Subsonic Transport

NASA's Ultra Efficient Engine Technology (UEET) program features advanced aeropropulsion technologies that include highly loaded turbomachinery, an advanced low-NOx combustor, high-temperature materials, intelligent propulsion controls, aspirated seal technology, and an advanced computational fluid dynamics (CFD) design tool to help reduce airplane drag. A probabilistic system assessment is performed to evaluate the impact of these technologies on aircraft fuel burn and NOx reductions. A 300-passenger aircraft, with two 396-kN thrust (85,000-pound) engines is chosen for the study. The results show that a large subsonic aircraft equipped with the UEET technologies has a very high probability of meeting the UEET Program goals for fuel-burn (or equivalent CO2) reduction (15% from the baseline) and LTO (landing and takeoff) NOx reductions (70% relative to the 1996 International Civil Aviation Organization rule). These results are used to provide guidance for developing a robust UEET technology portfolio, and to prioritize the most promising technologies required to achieve UEET program goals for the fuel-burn and NOx reductions

Breakthrough pain in oncology: a longitudinal study.

Abstract CONTEXT: Existing studies on breakthrough pain (BP) have reported different prevalence rates because of different settings, populations, and assessment methods. These studies have used cross-sectional designs, and the relationship of BP with analgesic treatment has not been evaluated. OBJECTIVES: The aim of this study was to longitudinally assess BP in cancer patients admitted to oncology units. METHODS: A consecutive sample of patients admitted to oncology centers was selected. At admission (T0), three months after admission (T3), and six months after admission (T6), data on background pain and BP were recorded. BP was assessed in terms of its intensity, duration, number of episodes, onset with movement, spontaneous relief after stopping activity, limitation of physical activity, and effectiveness of analgesics. RESULTS: Three hundred two patients completed the study. At T0, T3, and T6, 39%, 38%, and 33% patients, respectively, had continuous pain (P=0.294). Pain intensity significantly decreased (P=0.004 and 0.027 at T3 and T6, respectively). Most patients had BP at T0 (87.1%), T3 (80.9%), and T6 (73.2%), and there was a significant decrease in the prevalence of BP over time (P=0.016). Of 149 patients with BP, pain on movement was recorded in 43.6%, 43.4%, and 32.4% at T0, T3, and T6, respectively (P=0.228). Pain spontaneously decreased or ceased when stopping physical activity in 66%, 56%, and 62% at T0, T3, and T6, respectively (P=0.537). Pain on movement strongly limited physical activity in most patients. CONCLUSION: These data expand current information about BP and underline the need for a longitudinal assessment of a phenomenon that is invariably dependent on stage of disease, patient, and therapeutic factors

Bilateral transcranial direct current stimulation reshapes resting-state brain networks: A Magnetoencephalography assessment

Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders

Production of subject-verb agreement, tense, mood, and negation in Italian agrammatic aphasia

Impaired (morpho)syntactic production is the hallmark of agrammatic aphasia. Several hypotheses have been proposed to account for agrammatic production, which often make different predictions. The Distributed Morphology Hypothesis (DMH) (Wang et al., 2014) posits that categories involving inflectional alternations are impaired in agrammatism. The Tense Underspecification Hypothesis (TUH) (Wenzlaff & Clahsen, 2004, 2005) states that what is impaired (\u201cunderspecified\u201d) is tense; subject-verb agreement and mood are well-preserved. The Interpretable Features\u2019 Impairment Hypothesis (IFIH) (Fyndanis et al., 2012) predicts categories involving integration processes (e.g., tense, mood, negation) to be more impaired than categories that do not involve integration processes (e.g., agreement). The Tree Pruning Hypothesis (TPH) (Friedmann & Grodzinsky, 1997) states that the syntactic tree is pruned at a specific node, usually tense, with all nodes/categories above the pruning site deleted/inaccessible and all nodes below intact. To reliably test these accounts, one should test agrammatic speakers on a wide range of (morpho)syntactic phenomena/categories. In this study, we investigate the ability of Italian-speaking agrammatic individuals to produce subject-verb agreement, tense, mood, and sentential negation. A sentence completion task (SCT) tapping agreement and tense, a SCT assessing mood, and a constituent ordering task tapping negation were administered to eight native speakers of Italian with chronic agrammatic aphasia and eight controls. Results are presented in Table 1. The control group performed better than the aphasic group on all four conditions. Both groups showed similar patterns of performance, with better performance on agreement and tense than on mood. Negation was better preserved than agreement, tense, and mood in the aphasic group, but in the control group negation was not different from any other category. At the individual level, five agrammatic participants exhibited the same pattern of performance (agreement/tense/negation>mood). At the group level, the results of the agrammatic participants are not consistent with any of the hypotheses discussed here. Contrary to the TUH, participants performed better on tense than on mood. The DMH cannot explain the observed, selective impairment of categories involving inflectional alternations (tense/agreement>mood). Results do not support the TPH, as the higher the category in the syntactic hierarchy (Neg>T(future/past)>M) (Cinque, 1999; Zanuttini, 2001), the better the performance of agrammatic participants. Lastly, results are at odds with the IFIH, because negation (+integration processes) is better preserved than agreement (-integration processes). Analogous results are observed at the individual level. None of the available hypotheses can account for the patterns of performance of all the agrammatic participants. Their results, together with the production results of other agrammatic speakers in the literature, show that all possible patterns can be observed in agrammatism, and that a unitary account of the disorder is unlikely to succeed. We suggest that subject-specific characteristics (e.g., site/type/volume of brain damage, type/severity of language impairment, education, age) and language-specific properties of functional categories (e.g., syntactic hierarchy, interpretability/involvement of integration processes, frequency) may interact in determining the way in which (morpho)syntactic impairments manifest themselves across agrammatic speakers and languages

Genetic Modifiers of Cystic Fibrosis-Related Diabetes

Diabetes is a common age-dependent complication of cystic fibrosis (CF) that is strongly influenced by modifier genes. We conducted a genome-wide association study in 3,059 individuals with CF (644 with CF-related diabetes [CFRD]) and identified single nucleotide polymorphisms (SNPs) within and 5′ to the SLC26A9 gene that associated with CFRD (hazard ratio [HR] 1.38; P = 3.6 × 10−8). Replication was demonstrated in 694 individuals (124 with CFRD) (HR, 1.47; P = 0.007), with combined analysis significant at P = 9.8 × 10−10. SLC26A9 is an epithelial chloride/bicarbonate channel that can interact with the CF transmembrane regulator (CFTR), the protein mutated in CF. We also hypothesized that common SNPs associated with type 2 diabetes also might affect risk for CFRD. A previous association of CFRD with SNPs in TCF7L2 was replicated in this study (P = 0.004; combined analysis P = 3.8 × 10−6), and type 2 diabetes SNPs at or near CDKAL1, CDKN2A/B, and IGF2BP2 were associated with CFRD (P < 0.004). These five loci accounted for 8.3% of the phenotypic variance in CFRD onset and had a combined population-attributable risk of 68%. Diabetes is a highly prevalent complication of CF, for which susceptibility is determined in part by variants at SLC26A9 (which mediates processes proximate to the CF disease-causing gene) and at four susceptibility loci for type 2 diabetes in the general population

Nef divisors for moduli spaces of complexes with compact support

In [BM14b], the first author and Macr\`i constructed a family of nef divisors on any moduli space of Bridgeland-stable objects on a smooth projective variety X. In this article, we extend this construction to the setting of any separated scheme Y of finite type over a field, where we consider moduli spaces of Bridgeland-stable objects on Y with compact support. We also show that the nef divisor is compatible with the polarising ample line bundle coming from the GIT construction of the moduli space in the special case when Y admits a tilting bundle and the stability condition arises from a \theta-stability condition for the endomorphism algebra. Our main tool generalises the work of Abramovich--Polishchuk [AP06] and Polishchuk [Pol07]: given a t-structure on the derived category D_c(Y) on Y of objects with compact support and a base scheme S, we construct a constant family of t-structures on a category of objects on YxS with compact support relative to S.Comment: 36 pages. In memory of Johan Louis Dupont. V2: updated following comments from the referee and from Joe Karmazyn who gave a counterexample to a false claim in version 1. To appear in Selecta Mat