Aims: Sleep is altered during pregnancy, particularly during the third trimester. Low Vitamin D levels have been linked to shorter sleep duration, depression and anxiety. In the NiPPeR double-blind randomised controlled trial of nutritional supplementation, women received either a formulation with additional ingredients including Vitamin D (‘intervention group’) or standard prenatal vitamins (‘control group’). The association between Vitamin D deficiency, sleep, depression and anxiety was examined from pre-conception to six months post-partum. We aimed primarily to determine if women deficient in Vitamin D (<50nmol/L) were more likely to have disordered sleep compared with those Vitamin D sufficient. A secondary aim was to examine if women deficient in Vitamin D were more likely to be depressed or anxious compared with those with adequate Vitamin D levels.

Methods: We examined sleep data from women with at least one measurement of Vitamin D in the pregnancy and post-delivery periods (n=515). Pittsburgh Sleep Quality Index (PSQI) scores were compared between those with sufficient or deficient Vitamin D levels: by convention a PSQI score of >5 is considered to indicate disordered sleep. Depression was assessed using the Edinburgh Postnatal Depression Score (EPDS), with a score >13 indicating depression. The State-Trait Anxiety short form scale was used to measure anxiety, with a cut off >45 indicating state anxiety. One-way ANOVA in Stata version 18.0 was used throughout.

Results: As reported previously, the intervention substantially reduced the proportion of women who were Vitamin D deficient during pregnancy but did not change EPDS scores; PSQI scores were also not changed by the intervention. In the combined control and intervention group total PSQI scores increased from pre-conception until six weeks post-delivery. Total hours of sleep declined from pregnancy weeks 19–20 to six weeks post-delivery. At recruitment preconception, PSQI scores were higher in those deficient in Vitamin D, compared with those with sufficient levels (p=0.015); at later time-points PSQI scores were higher in Vitamin D deficient women but not significantly so. Depression as assessed by EPDS >13 was associated with Vitamin D deficiency only at preconception recruitment (p=0.019) and at 7 weeks’ gestation (p=0.004), but not later in pregnancy or post-delivery. There was no association found between anxiety and Vitamin D status.

Conclusion: At pre-conception, sleep was worse in women with low Vitamin D levels. At preconception and early in pregnancy, low Vitamin D levels were associated with depression. Intervention with a Vitamin D containing supplement did not improve sleep in pregnant women.

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.

Few studies have examined functional connectivity (FC) patterns using functional magnetic resonance imaging (fMRI) to predict outcomes in late-life depression. We hypothesized that FC within and between frontal and limbic regions would be associated with 12-week depression outcome in older depressed adults. Seventy-one subjects with major depression were enrolled in the study. A study geriatric psychiatrist performed a clinical interview and completed a Montgomery-Åsberg Depression Rating Scale (MADRS). All study participants were free of medication at baseline and had a brain fMRI scan. Using a regions of interest (ROI) atlas (including 164 ROIs), we conducted ROI-to-ROI resting-state FC analyses for each participant. In terms of treatment participants were offered sertraline initially, although in this naturalistic study, other medications were also prescribed. Subjects were evaluated every 2 weeks up to 12 weeks by the study psychiatrist, who followed a flexible, clinically based medication dosing schedule. Multivariate regression analysis was used to examine correlation between change of MADRS score over 12 weeks and baseline FC between brain regions, controlling for age, gender, mean head motion, and baseline MADRS. We found greater FC between the left inferior frontal gyrus pars triangularis and the left frontal eye field and FC of these two regions with a number of brain regions related to reward, salience, and sensorimortor function were correlated with change in MADRS score over 12 weeks. Our results highlight the important role of between inner speech-reward, attention-salience, and attention-sensorimotor network synchronization in predicting acute treatment response in late-life depression.

The ‘Landscapes of Production and Punishment’ project aims to examine how convict labour from 1830–1877 affected the built and natural landscapes of the Tasman Peninsula, as well as the lives of the convicts themselves.

Older people living in long-term facilities (nursing and residential homes providing 24-hour care) spend the majority of their time inactive, despite the known health and wellbeing benefits of physical activity and reduced time spent sedentary. In order to successfully embed interventions that aim to increase physical activity or reduce sedentary behaviour, it is necessary to understand the features of the care environment that influence residents’ routine patterns of movement. Drawing on an organisational perspective, this paper explores the structures and mechanisms that shaped different care practices concerning residents’ movement in two contrasting care homes in the north of England. This study adopted an ethnographic approach, using a combination of qualitative observations, informal conversations and interviews. A grounded theory approach to data analysis was adopted. The findings illustrate the importance of translating espoused values of care into tangible and acceptable care practices, systems of management, staff training and development, and the use of care planning in residents’ routine patterns of movement. Understanding how organisational factors shape routine movement among care home residents will help inform the development of embedded and sustainable interventions that enhance physical activity and reduce sedentary behaviour. This study is part of a wider programme of research developing and testing a complex intervention, embedded within routine care, to reduce sedentary behaviour among care home residents.

An extensive late Quaternary fauna, including many extinct giant lemurs, has been collected recently in a 110+-km system of caves in the Ankarana Massif of northern Madagascar. AMS 14C dates for the acid-insoluble (collagen/gelatin) fraction of bones of the giant lemur Megaladapis (26,150 ± 400 and 12,760 ± 70 yr B.P.) confirm its presence in the area during the late Pleistocene and provide the first Pleistocene 14 C ages from bones of the extinct megafauna of the island. The first date from bones of the recently described extinct Babakotia radofilai (4400 ± 60 yr B.P.) shows that it was present in northern Madagascar in mid-Holocene times. A comparatively recent age of 1020 ± 50 yr B.P. for the extinct Archaeolemur indicates survival of this genus for at least a millennium after the first direct evidence for humans in Madagascar. This suggests that the island's "extinction window" may have represented a longer time span than would have been expected under the Blitzkrieg model of late Quaternary extinctions. A mid-Holocene age (4560 ± 70 yr B.P.) for a bone sample of the small extant lemur Hapalemur simus indicates that the disappearance of this now-restricted species from the Ankarana occurred after this date. New data from the Ankarana and other sites on the island add to the consensus that major biotic changes occurred on Madagascar in the late Holocene.

Most inland eolian dunes associated with rivers on the Georgia Coastal Plain probably date to glacial periods. Direct dating of the dune sand by optically stimulated luminescence dating, combined with limiting ages from radiocarbon dating, shows that dunes formed during isotope stage 2, stage 3, the transition between stages 4 and 5, and isotope stage 6 or earlier. Most of the dates indicate dune activity between 30,000 and 15,000 years ago. Holocene activity included limited and local reworking of the crests of some thick dunes along streams that flow from the Piedmont.