The Blue Hills Igneous Complex Boston Area, Massachusetts

Guidebook for field trips to the Boston area and vicinity : 68th annual meeting, New England Intercollegiate Geological Conference, October 8-10, 1976: Trip A-3; B-

Submillimetre line spectrum of the Seyfert galaxy NGC1068 from the Herschel-SPIRE Fourier Transform Spectrometer

The first complete submillimetre spectrum (190-670um) of the Seyfert 2 galaxy NGC1068 has been observed with the SPIRE Fourier Transform Spectrometer onboard the {\it Herschel} Space Observatory. The sequence of CO lines (Jup=4-13), lines from water, the fundamental rotational transition of HF, two o-H_2O+ lines and one line each from CH+ and OH+ have been detected, together with the two [CI] lines and the [NII]205um line. The observations in both single pointing mode with sparse image sampling and in mapping mode with full image sampling allow us to disentangle two molecular emission components, one due to the compact circum-nuclear disk (CND) and one from the extended region encompassing the star forming ring (SF-ring). Radiative transfer models show that the two CO components are characterized by density of n(H_2)=10^4.5 and 10^2.9 cm^-3 and temperature of T=100K and 127K, respectively. The comparison of the CO line intensities with photodissociation region (PDR) and X-ray dominated region (XDR) models, together with other observational constraints, such as the observed CO surface brightness and the radiation field, indicate that the best explanation for the CO excitation of the CND is an XDR with density of n(H_2) 10^4 cm^-3 and X-ray flux of 9 erg s^-1 cm^-2, consistent with illumination by the active galactic nucleus, while the CO lines in the SF-ring are better modeled by a PDR. The detected water transitions, together with those observed with the \her \sim PACS Spectrometer, can be modeled by an LVG model with low temperature (T_kin \sim 40K) and high density (n(H_2) in the range 10^6.7-10^7.9 cm^-3).Comment: Accepted for publication on the Astrophysical Journal, 30 August 201

The geography of health knowledge/s

publication-status: Publishedtypes: Editorial CommentCopyright © 2004 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Health and Place, 2004, Vol. 10, Issue 4, pp. pp. 293 - 297 DOI: 10.1016/j.healthplace.2004.07.003Editoria

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent In Vitro Antileishmanial Activity:Initial SAR and Assessment of In Vivo Activity

Visceral leishmaniasis (VL) is a parasitic infection that results in approximately 26,000 - 65,000 deaths annually. The available treatments are hampered by issues such as toxicity, variable efficacy and unsuitable dosing options. The need for new treatments is urgent and led to a collaboration between the Drugs for Neglected Diseases initiative (DNDi), GlaxoSmithKline (GSK) and the University of Dundee. An 8-hydroxynaphthyridine was identified as a start point and an early compound demonstrated weak efficacy in a mouse model of VL but was hampered by glucuronidation. Efforts to address this led to the development of compounds with improved in vitro profiles, but these were poorly tolerated in vivo. Investigation of the mode of action (MoA) demonstrated that activity was driven by sequestration of divalent metal cations, a mechanism which was likely to drive the poor tolerability. This highlights the importance of investigating MoA and pharmacokinetics at an early stage for phenotypically active series.</p

Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion

The soluble and membrane-anchored isoforms of Mgm1 are only active when they work together (in trans)

Long-term declines in ADLs, IADLs, and mobility among older Medicare beneficiaries

<p>Abstract</p> <p>Background</p> <p>Most prior studies have focused on short-term (≤ 2 years) functional declines. But those studies cannot address aging effects inasmuch as all participants have aged the same amount. Therefore, the authors studied the extent of long-term functional decline in older Medicare beneficiaries who were followed for varying time lengths, and the authors also identified the risk factors associated with those declines.</p> <p>Methods</p> <p>The analytic sample included 5,871 self- or proxy-respondents who had complete baseline and follow-up survey data that could be linked to their Medicare claims for 1993-2007. Functional status was assessed using activities of daily living (ADLs), instrumental ADLs (IADLs), and mobility limitations, with declines defined as the development of two of more new difficulties. Multiple logistic regression analysis was used to focus on the associations involving respondent status, health lifestyle, continuity of care, managed care status, health shocks, and terminal drop.</p> <p>Results</p> <p>The average amount of time between the first and final interviews was 8.0 years. Declines were observed for 36.6% on ADL abilities, 32.3% on IADL abilities, and 30.9% on mobility abilities. Functional decline was more likely to occur when proxy-reports were used, and the effects of baseline function on decline were reduced when proxy-reports were used. Engaging in vigorous physical activity consistently and substantially protected against functional decline, whereas obesity, cigarette smoking, and alcohol consumption were only associated with mobility declines. Post-baseline hospitalizations were the most robust predictors of functional decline, exhibiting a dose-response effect such that the greater the average annual number of hospital episodes, the greater the likelihood of functional status decline. Participants whose final interview preceded their death by one year or less had substantially greater odds of functional status decline.</p> <p>Conclusions</p> <p>Both the additive and interactive (with functional status) effects of respondent status should be taken into consideration whenever proxy-reports are used. Encouraging exercise could broadly reduce the risk of functional decline across all three outcomes, although interventions encouraging weight reduction and smoking cessation would only affect mobility declines. Reducing hospitalization and re-hospitalization rates could also broadly reduce the risk of functional decline across all three outcomes.</p

The aging clock: circadian rhythms and later life

Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes