To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI).
We ...followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria.
Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk RR = 1.8 1.2 to 2.7 per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 1.0 to 3.6 per symptom).
The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.
Abstract Children who have been exposed to maltreatment and other adverse childhood experiences (ACEs) are at increased risk for various negative adult health outcomes, including cancer, liver ...disease, substance abuse, and depression. However, the proximal associations between ACEs and behavioral outcomes during the middle childhood years have been understudied. In addition, many of the ACE studies contain methodological limitations such as reliance on retrospective reports and limited generalizability to populations of lower socioeconomic advantage. The current study uses data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort, to prospectively assess the adverse experiences and subsequent behavior problems of over 3000 children. Eight ACE categories to which a child was exposed by age 5 were investigated: childhood abuse (emotional and physical), neglect (emotional and physical), and parental domestic violence, anxiety or depression, substance abuse, or incarceration. Results from bivariate analyses indicated that Black children and children with mothers of low education were particularly likely to have been exposed to multiple ACE categories. Regression analyses showed that exposure to ACEs is strongly associated with externalizing and internalizing behaviors and likelihood of ADHD diagnosis in middle childhood. Variation in these associations by racial/ethnic, gender, and maternal education subgroups are examined. This study provides evidence that children as young as 9 begin to show behavioral problems after exposure to early childhood adversities.
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The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical ...diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at‐risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain‐based) in order to increase prediction accuracy.
It is well-known that superconductivity in thin films is generally suppressed with decreasing thickness. This suppression is normally governed by either disorder-induced localization of Cooper pairs, ...weakening of Coulomb screening, or generation and unbinding of vortex–antivortex pairs as described by the Berezinskii–Kosterlitz–Thouless (BKT) theory. Defying general expectations, few-layer NbSe2, an archetypal example of ultrathin superconductors, has been found to remain superconducting down to monolayer thickness. Here, we report measurements of both the superconducting energy gap Δ and critical temperature T C in high-quality monocrystals of few-layer NbSe2, using planar-junction tunneling spectroscopy and lateral transport. We observe a fully developed gap that rapidly reduces for devices with the number of layers N ≤ 5, as does their T C. We show that the observed reduction cannot be explained by disorder, and the BKT mechanism is also excluded by measuring its transition temperature that for all N remains very close to T C. We attribute the observed behavior to changes in the electronic band structure predicted for mono- and bi- layer NbSe2 combined with inevitable suppression of the Cooper pair density at the superconductor-vacuum interface. Our experimental results for N > 2 are in good agreement with the dependences of Δ and T C expected in the latter case while the effect of band-structure reconstruction is evidenced by a stronger suppression of Δ and the disappearance of its anisotropy for N = 2. The spatial scale involved in the surface suppression of the density of states is only a few angstroms but cannot be ignored for atomically thin superconductors.
Phytopathogen infection leads to changes in secondary metabolism based on the induction of defence programmes as well as to changes in primary metabolism which affect growth and development of the ...plant. Therefore, pathogen attack causes crop yield losses even in interactions which do not end up with disease or death of the plant. While the regulation of defence responses has been intensively studied for decades, less is known about the effects of pathogen infection on primary metabolism. Recently, interest in this research area has been growing, and aspects of photosynthesis, assimilate partitioning, and source-sink regulation in different types of plant-pathogen interactions have been investigated. Similarly, phytopathological studies take into consideration the physiological status of the infected tissues to elucidate the fine-tuned infection mechanisms. The aim of this review is to give a summary of recent advances in the mutual interrelation between primary metabolism and pathogen infection, as well as to indicate current developments in non-invasive techniques and important strategies of combining modern molecular and physiological techniques with phytopathology for future investigations.
Rockfall is an extremely rapid process involving long travel distances. Due to these features, when an event occurs, the ability to take evasive action is practically zero and, thus, the risk of ...injury or loss of life is high. Damage to buildings and infrastructure is quite likely. In many cases, therefore, suitable protection measures are necessary. This contribution provides an overview of previous and current research on the main topics related to rockfall. It covers the onset of rockfall and runout modelling approaches, as well as hazard zoning and protection measures. It is the aim of this article to provide an in-depth knowledge base for researchers and practitioners involved in projects dealing with the rockfall protection of infrastructures, who may work in the fields of civil or environmental engineering, risk and safety, the earth and natural sciences.
The foot of Homo naledi Harcourt-Smith, W E H; Throckmorton, Z; Congdon, K A ...
Nature communications,
10/2015, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated ...remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having more curved proximal pedal phalanges, and features suggestive of a reduced medial longitudinal arch. Within the context of primitive features found elsewhere in the skeleton, these findings suggest a unique locomotor repertoire for H. naledi, thus providing further evidence of locomotor diversity within both the hominin clade and the genus Homo.
Highlight • We report high and low trajectories of acute CSF IL-6. The high group had higher acute CSF and sub-acute serum inflammation, and were at high risk for poor outcomes at 6 and 12 mos.
We present UV, optical, and near-infrared (NIR) photometry of the first electromagnetic counterpart to a gravitational wave source from Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo, the binary neutron star merger GW170817. Our data set extends from the discovery of the optical counterpart at 0.47-18.5 days post-merger, and includes observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2 (GS/F2), and the Hubble Space Telescope (HST). The spectral energy distribution (SED) inferred from this photometry at 0.6 days is well described by a blackbody model with T 8300 K, a radius of R 4.5 × 10 14 cm (corresponding to an expansion velocity of v 0.3 c ), and a bolometric luminosity of L bol 5 × 10 41 erg s−1. At 1.5 days we find a multi-component SED across the optical and NIR, and subsequently we observe rapid fading in the UV and blue optical bands and significant reddening of the optical/NIR colors. Modeling the entire data set, we find that models with heating from radioactive decay of 56Ni, or those with only a single component of opacity from r-process elements, fail to capture the rapid optical decline and red optical/NIR colors. Instead, models with two components consistent with lanthanide-poor and lanthanide-rich ejecta provide a good fit to the data; the resulting "blue" component has M ej blue 0.01 M and v ej blue 0.3 c , and the "red" component has M ej red 0.04 M and v ej red 0.1 c . These ejecta masses are broadly consistent with the estimated r-process production rate required to explain the Milky Way r-process abundances, providing the first evidence that binary neutron star (BNS) mergers can be a dominant site of r-process enrichment.
Biliary tract cancer (BTC) has a high mortality. Primary diagnosis is frequently delayed due to mostly unspecific symptoms, resulting in a high number of advanced cases at the time of diagnosis. ...Advanced BTCs are in principle chemotherapy sensitive as determined by improved disease control, survival and quality of life (QoL). However, median OS does not exceed 11.7 months with the current standard of care gemcitabine plus cisplatin. Thereby, novel drug formulations like nanoliposomal-irinotecan (nal-IRI) in combination with 5- fluorouracil (5-FU)/leucovorin may have the potential to improve therapeutic outcomes in this disease.
NIFE is an interventional, prospective, randomized, controlled, open label, two-sided phase II study. Within the study, 2 × 46 patients with locally advanced, non-resectable or metastatic BTC are to be enrolled by two stage design of Simon. Data analysis will be done unconnected for both arms. Patients are allocated in two arms: Arm A (experimental intervention) nal-IRI mg/m
, 46 h infusion)/5-FU (2400 mg/m
, 46 h infusion)/leucovorin (400 mg/m
, 0.5 h infusion) d1 on 14 day-cycles; Arm B (standard of care) cisplatin (25 mg/m
, 1 h infusion)/gemcitabine (1000 mg/m
, 0.5 h infusion) d1 and d8 on 21 day-cycles. The randomization (1:1) is stratified for tumor site (intrahepatic vs. extrahepatic biliary tract), disease stage (advanced vs. metastatic), age (≤70 vs. > 70 years), sex (male vs. female) and WHO performance score (ECOG 0 vs. ECOG 1). Primary endpoint of the study is the progression free survival (PFS) rate at 4 months after randomization by an intention-to-treat analysis in each of the groups. Secondary endpoints are the overall PFS rate, the 3-year overall survival rate, the disease control rate after 2 months, safety and patient related outcome with quality of life. The initial assessment of tumor resectability for locally advanced BTCs is planned to be reviewed retrospectively by a central surgical board. Exploratory objectives aim at establishing novel biomarkers and molecular signatures to predict response. The study was initiated January 2018 in Germany.
The NIFE trial evaluates the potential of a nanoliposomal-irinotecan/5-FU/leucovorin combination in the first line therapy of advanced BTCs and additionally offers a unique chance for translational research.
Clinicaltrials.gov NCT03044587. Registration Date February 7th 2017.
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