The flyby of Pluto and Charon by the New Horizons spacecraft provided high-resolution images of cratered surfaces embedded in the Kuiper belt, an extensive region of bodies orbiting beyond Neptune. ...Impact craters on Pluto and Charon were formed by collisions with other Kuiper belt objects (KBOs) with diameters from ~40 kilometers to ~300 meters, smaller than most KBOs observed directly by telescopes. We find a relative paucity of small craters ≲13 kilometers in diameter, which cannot be explained solely by geological resurfacing. This implies a deficit of small KBOs (≲1 to 2 kilometers in diameter). Some surfaces on Pluto and Charon are likely ≳4 billion years old, thus their crater records provide information on the size-frequency distribution of KBOs in the early Solar System.
It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function – ...inhibition – by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.
Abstract
We used existing data from the New Horizons Long-range Reconnaissance Imager (LORRI) to measure the optical-band (0.4 ≲
λ
≲ 0.9
μ
m) sky brightness within seven high–Galactic latitude ...fields. The average raw level measured while New Horizons was 42–45 au from the Sun is 33.2 ± 0.5 nW m
−2
sr
−1
. This is ∼10× as dark as the darkest sky accessible to the Hubble Space Telescope, highlighting the utility of New Horizons for detecting the cosmic optical background (COB). Isolating the COB contribution to the raw total required subtracting scattered light from bright stars and galaxies, faint stars below the photometric detection limit within the fields, and diffuse Milky Way light scattered by infrared cirrus. We removed newly identified residual zodiacal light from the IRIS 100
μ
m all-sky maps to generate two different estimates for the diffuse Galactic light. Using these yielded a highly significant detection of the COB in the range 15.9 ± 4.2 (1.8 stat., 3.7 sys.) nW m
−2
sr
−1
to 18.7 ± 3.8 (1.8 stat., 3.3 sys.) nW m
−2
sr
−1
at the LORRI pivot wavelength of 0.608
μ
m. Subtraction of the integrated light of galaxies fainter than the photometric detection limit from the total COB level left a diffuse flux component of unknown origin in the range 8.8 ± 4.9 (1.8 stat., 4.5 sys.) nW m
−2
sr
−1
to 11.9 ± 4.6 (1.8 stat., 4.2 sys.) nW m
−2
sr
−1
. Explaining it with undetected galaxies requires the assumption that the galaxy count faint-end slope steepens markedly at
V
> 24 or that existing surveys are missing half the galaxies with
V
< 30.
Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the ...natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis.
A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and Hoehn-Yahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr‘aphic, clinical and genetic variables was evaluated using survival analysis.
Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (Hoehn-Yahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life.
Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.
Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of ...seroconversion is unknown.
We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4years (IQR=6–11years, range=0–40years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay).
HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1–155.4) in whites and 17.2-fold (95% CI 1.7–170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30years (N=24), 20–30years (N=148), 10–20years (N=228), and <10years (N=301 cases) (p-trend<0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25years before diagnosis.
The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.
We have previously performed detailed clinical and neuropsychological assessments in a community-based cohort of patients with newly diagnosed parkinsonism, and through analysis of a subcohort with ...idiopathic Parkinson's disease (PD), we have demonstrated that cognitive dysfunction occurs even at the time of PD diagnosis and is heterogeneous. Longitudinal follow-up of the cohort has now been performed to examine the evolution of cognitive dysfunction within the early years of the disease. One hundred and eighty (79%) eligible patients from the original cohort with parkinsonism were available for re-assessment at between 3 and 5 years from their initial baseline assessments. PD diagnoses were re-validated with repeated application of the UKPDS Brain Bank criteria in order to maximize sensitivity and specificity, following which a diagnosis of idiopathic PD was confirmed in 126 patients. Thirteen out of 126 (10%) had developed dementia at a mean (SD) of 3.5 (0.7) years from diagnosis, corresponding to an annual dementia incidence of 30.0 (16.4-52.9) per 1000 person-years. A further 57% of PD patients showed evidence of cognitive impairment, with frontostriatal deficits being most common amongst the non-demented group. However, the most important clinical predictors of global cognitive decline following correction for age were neuropsychological tasks with a more posterior cortical basis, including semantic fluency and ability to copy an intersecting pentagons figure, as well as a non-tremor dominant motor phenotype at the baseline assessment. This work clarifies the profile of cognitive dysfunction in early PD and demonstrates that the dementing process in this illness is heralded by both postural and gait dysfunction and cognitive deficits with a posterior cortical basis, reflecting probable non-dopaminergic cortical Lewy body pathology. Furthermore, given that these predictors of dementia are readily measurable within just a few minutes in a clinical setting, our work may ultimately have practical implications in terms of guiding prognosis in individual patients.
Objective: To investigate the heterogeneity of idiopathic Parkinson’s disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established ...diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson’s disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment.
The precise localization of executive functions such as response inhibition within the prefrontal cortex (PFC), although theoretically crucial, has proven to be controversial and difficult. ...Functional neuroimaging has contributed importantly to this debate, but as human cortical lesions are seldom discrete, the literature still lacks definitive neuropsychological evidence that a specific region is necessary for task performance. We overcame this limitation by using a new observer-independent method to relate the degree of damage within a specific prefrontal region to performance on a stop-signal task that is sensitive to the neurodevelopmental aspects of stopping behavior and to attention-deficit/hyperactivity disorder (ADHD) as well as its amelioration by methylphenidate.
Background
Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear.
Objective
To investigate the association ...between subclinical thyroid dysfunction and bone loss.
Methods
Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946–2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid‐stimulating hormone TSH 0.45–4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50–19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X‐ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random‐effects two‐step approach.
Results
Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person‐years of follow‐up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = −0.18 (95% CI: −0.34, −0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = −0.14 (95% CI: −0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: −0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = −0.59; 95% CI: −0.99, −0.19) and total hip region (%ΔBMD = −0.46 95% CI: −1.05, −0.13). In contrast, SHypo was not associated with bone loss at any site.
Conclusion
Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.
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