Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.

We present macrobotanical, starch, and phytolith data from artifacts and sediments from Middle Formative La Blanca (1000–600 cal BC) and Late Formative El Ujuxte (600 cal BC–cal AD 115 ) in the Soconusco region in Guatemala. Potential economic plants identified included palm (cf. Arecaceae), two varieties of maize (Zea mays), guava (Psidium guajava), bean (Phaseolus), chili peppers (Capsicum), squash (Cucurbitaceae), custard apple (Annonaceae), coco plum (Chrysobalanaceae), lerén (Calathea), arrowroot (Maranta), and bird-of-paradise (Heliconia). The results suggest that control of food production and consumption was critical for the transition from complex chiefdoms during the Middle Formative to the archaic state in the Late Formative. The arrival of a more productive South American variety of maize at El Ujuxte (about 2549 BP) allowed elites to exploit an already existing broad-based economic system and to use the maize-based religious system to increase control over maize agricultural practices and maintain power through ideology and disciplinary power. These data suggest that the arrival of fully domesticated South American maize likely influenced the overall development of Mesoamerican state-level societies.

Secondary ion mass spectrometry (SIMS) techniques have been used to study the variation of C isotope ratio and N abundance within selected diamonds in relation to their crystal growth zones. The growth zones are seen in cathodoluminescence (CL), and include both octahedral and cuboid zones within typical diamonds of external octahedral morphology. Compositions were determined by use of a primary 133Cs+ ion beam and measurement of 12C−, 13C, and 12C14N− secondary ions at high mass resolution on a Cameca ims-4f ion microprobe at Edinburgh University.

In each of the diamonds, different growth zones have marked differences in N abundance, which are as great as 0–1400 ppm within one diamond. Changes of several hundred ppm N are common across both octahedral and cuboid growth zones, and appear sharp and abrupt at the boundaries of the growth zones. In general for the common blue CL, luminescence increases with N abundance. The changes in N abundance across fine scale (∼100 µm) growth zones show that the total N contents determined by IR spectroscopy may show great variations of abundance. In contrast, within detection limits, δ13C appears constant across many growth zone boundaries. Thus the factors controlling uptake of N from the fluid/melt reservoir in which natural diamonds grow often do not influence δ13C. No evidence of progressive variation or fractionation of C isotopes during growth was found.

Some original variation in C isotope composition may have been eliminated by diffusion of C atoms subsequent to growth, because of the storage of natural diamonds over millions of years in the Earth's mantle at temperatures of 950–1250°C. Such atomic mobility does not homogenize N distribution because of the proven tendency of N to form aggregates of atoms. A survey of experimental estimates of single atom (C) diffusion parameters, suggests that diffusion distances of ∼100 µm are likely at high temperatures (∼1100°C) over long time periods (∼1.0 Ga). Therefore, with refinement of the diffusion parameters and measurements, the extent of C isotope homogenization in natural diamonds, as well as N aggregation state, might provide quantitative evidence of their time-temperature history under mantle conditions.

Diamonds from George Creek, Colorado, preserve complex intergrowth textures between two major growth generations: homogeneous diamond with yellow-buff cathodoluminescence (CL); and diamond with blue-green CL and local growth zonation. Secondary-ion mass spectrometry (SIMS) has revealed large variations in N concentration and C isotope composition within these diamonds. Even within single stones, N contents and δ13C values can vary from 0 to 750 ppm and 0 to −20‰ respectively. These variations are similar to those recorded elsewhere for entire diamond suites. The CL characteristics correlate directly with N: diamond with yellow-buff CL has uniform N contents, whereas the zoned diamond has bright blue CL bands with high N (50–750 ppm) and dark blue or green CL bands with low N (0–20 ppm). These bands are too narrow (10–5 µm) for analysis by IR spectroscopy. δ13C also varies between the two growth generations in any one diamond plate, and to a lesser extent within these generations, but shows no consistent correlations with either CL or N. The George Creek stones preserve evidence of extreme temporal and/or spatial variations in both δ13C and N concentrations during the period of diamond growth, but the factors controlling N content during diamond growth did not control δ13C.

Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.

Analytical precision is vital in the interpretation of stable isotope data collected by secondary ion mass spectrometry (SIMS) given the small analysis volumes and the small magnitude of natural isotopic variations. The observed precision of a set of measurements is represented by the standard deviation(precision of an individual measurement) or the standard error of the mean (precision of the mean value). The SIMS data show both systematic variations with time and random Poisson variability, but the former largely cancel out when data for two different isotopes are expressed as a ratio. The precision of a SIMS isotope ratio routinely matches that predicted by Poisson counting statistics and can approach that of conventional bulk analysis techniques for counting times of several hours. All sample analyse must be calibrated for instrumental mass fractionation using SIMS analyses of a standard material. There is often a gradual drift in the mass fractionation with time, but this can be modelled by least-squares regression of the standard isotope ratios. Drift in the sample analyses is eliminated by using the relevant point on this regression line to calibrate each sample. The final precision of a corrected isotope ratio must take into account the scatter in both the sample and the standard data.

In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; P<0.01; day 11: calm 1.83; nervous 1.57; P<0.05). Ovulation rate on day 11 in nervous ewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; P<0.01). Reproductive loss between days 30 and 74 represented 7.3% of the overall loss. Temperament did not affect concentrations of progesterone, but nervous ewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect differences in energy utilisation.

Evidence from the Ross embayment, Antarctica, suggests an abrupt cooling and a concomitant increase in sea-ice cover at about 6000 BP (6 ka). Stable-isotope (δD) concentrations in the Taylor Dome ice core, at the western edge of the Ross embayment, decline rapidly after 6 ka, and continue to decline through the late Holocene. Methanesulfonic acid concentrations at Taylor Dome show opposite trends to δD Sediment cores from the western Ross Sea show a percentage minimum for the sea-ice diatom Fragilariopsis curta between 9 and 6 ka, whenTaylor Dome δD values are highest, followed by an increase through the late Holocene. Radiocarbon dates from raised beach deposits indicate that the retreat of ice shelves in the Ross embayment ceased at about 6 ka, coincident with the environmental changes inferred from the sediment and ice-core records. The similarity in timing suggests an important role for climate in controlling the evolution of ice-shelf margins following the end of the last glaciation.

Convection from an isolated heat source in a chamber has been previously studied numerically, experimentally and analytically. These have not covered long time spans for wide ranges of Rayleigh number Ra and Prandtl number Pr. Numerical calculations of constant viscosity convection partially fill the gap in the ranges $\mathit{Ra}= 1{0}^{3} {{\unicode{x2013}}}1{0}^{6} $ and $\mathit{Pr}= 1, 10, 100, 1000$ and $\infty $ . Calculations begin with cold fluid everywhere and localized hot temperature at the centre of the bottom of a square two-dimensional chamber. For $\mathit{Ra}\gt 20\hspace{0.167em} 000$ , temperature increases above the hot bottom and forms a rising plume head. The head has small internal recirculation and minor outward conduction of heat during ascent. The head approaches the top, flattens, splits and the two remnants are swept to the sidewalls and diffused away. The maximum velocity and the top centre heat flux climb to maxima during head ascent and then adjust toward constant values. Two steady cells are separated by a vertical thermal conduit. This sequence is followed for every value of $Pr$ number, although lower Pr convection lags in time. For $\mathit{Ra}\lt 20\hspace{0.167em} 000$ there is no plume head, and no streamfunction and heat flux maxima with time. For sufficiently large Ra and all values of Pr, an oscillation develops at roughly $t= 0. 2$ , with the two cells alternately strengthening and weakening. This changes to a steady flow with two unequal cells that at roughly $t= 0. 5$ develops a second oscillation.