We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34(+)-cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological ...reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34(+) cells (median: 22 × 10(6)/kg) with a fixed dose of 3 × 10(4)/kg CD3(+) cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34(+) cells with a fixed CD3(+) cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.
Mobile marine species can exhibit vast movements both horizontally and vertically. Spatial analysis of vertical movements may help improve an understanding of the processes that influence space use. ...Previously, vertical space use of basking sharks (
Cetorhinus maximus
) in the north-east Atlantic described movements largely within waters of the continental shelf during summer and autumn months, with few records of detailed vertical behaviour during winter. We use archival satellite telemetry data from 32 basking sharks (12 females, 6 males, and 14 of unknown sex measuring 4–5 m (
n
= 6), 5–6 m (
n
= 10), 6–7 m (
n
= 7), 7–8 m (
n
= 8), and 8–9 m (
n
= 1) estimated total length) tracked over 4 years (2012–2015). The satellite tags provided depth and temperature data for a cumulative 4489 days (mean 140 ± 97 days per shark, range 10–292 days) to describe vertical space use and thermal range of basking sharks in the north-east Atlantic. Basking sharks exhibit seasonality in vertical space use, revealing repeated ‘yo-yo’ movement behaviour with periods of occupancy at depths greater than 1000 m in late winter/early spring. Describing seasonal vertical space use in marine megavertebrates can increase knowledge of movements throughout their environment including physiological and morphological constraints to movement, nutrient transfer, and overlap with anthropogenic threats to inform future conservation strategies.
Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits.
A ...literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment.
At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus.
OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.
Management strategies are needed to optimise the number of piglets weaned from hyper-prolific sows. Nurse sow strategies involve transferring supernumerary new-born piglets onto a sow whose own ...piglets are either weaned or fostered onto another sow. Such 'nurse sows' have extended lactations spent in farrowing crates, which could have negative implications for their welfare. This study used 47 sows, 20 of which farrowed large litters and had their biggest piglets fostered onto nurse sows which were either 1 week (2STEP7, n=9) or 3 weeks into lactation (1STEP21, n=10). Sows from which piglets were removed (R) were either left with the remainder of the litter intact (I) (remain intact (RI) sows, n=10), or had their litters equalised (E) for birth weight using piglets of the same age from non-experimental sows (remain equalised (RE) sows, n=9). Piglets from 2STEP7 were fostered onto another nurse sow which was 3 weeks into lactation (2STEP21, n=9). Back-fat thickness was measured at entry to the farrowing house, at fostering (nurse sows only) and weaning. Sows were scored for ease of locomotion and skin and claw lesions at entry to the farrowing house and weaning. Salivary cortisol samples were collected and tear staining was scored at 0900 h weekly from entry until weaning. Saliva samples were also taken at fostering. Data were analysed using GLMs with appropriate random and repeated factors, or non-parametric tests were applied where appropriate. Back-fat thickness decreased between entry and weaning for all sows (F 1,42=26.59, P<0.001) and tended to differ between treatments (F 4,16=2.91; P=0.06). At weaning RI sows had lower limb lesion scores than 2STEP7 and RE sows (χ 2 4=10.8, P0.05) and all nurse sows had a higher salivary cortisol concentration at fostering, compared with the other days (F 10,426=3.47; P<0.05). Acute effects of fostering differed between nurse sow treatments (F 2,113=3.45, P0.05). In conclusion, no difference was detected between nurse sows and non-nurse sows in body condition or severity of lesions. Although some nurse sows experienced stress at fostering, no long-term effect of the nurse sow strategies was detected on stress levels compared with sows that raised their own litter.
Nurse sow strategies are used to manage large litters on commercial pig farms. However, new-born piglets transferred to nurse sows in late lactation might be compromised in terms of growth and ...survival. We investigated the effects of two nurse sow strategies on piglet growth, suckling behaviour and sow nursing behaviour. At 1-day post-farrowing, the four heaviest piglets from large litters were transferred to a nurse sow either 21 (1STEP21, n=9 litters) or 7 (2STEP7, n=10 litters) days into lactation. The remainder of the litter remained with their mother and was either kept intact (remain intact (RI), n=10 litters) or had some piglets cross-fostered to equalise birth weights (remain equalised (RE), n=9 litters). The 7-day-old piglets from 2STEP7 were transferred onto a sow 21 days into lactation (2STEP21, n=10 litters). The growth of new-born piglets on 1STEP21 and 2STEP7 nurse sows was initially lower than in RI litters (F 3,33.8=4.61; P<0.01), but weaning weights did not significantly differ (F 4,32.7=0.78; P>0.5). After the 1st week of lactation, the weights and growth rates did not differ between treatments. Fighting behaviour during nursing bouts decreased over time. The frequency of fights was higher in 1STEP21 and 2STEP21 litters compared with RI litters (t 122=3.06 and t 123=3.00, respectively, P<0.05). The 2STEP21 litters had shorter nursing bouts than RI and 1STEP21 litters (t 107=-2.81 and t 81.7=2.8, respectively, P<0.05), which were more frequently terminated by 2STEP21 than RI sows (t 595=2.93; P<0.05). Transferring heaviest piglets from RI and RE litters to nurse sows reduced the percentage of teat changes during nursing bouts (RI: F 1,275=16.61; RE: F 1,308=43.59; P<0.001). In conclusion, nurse sow strategies do not appear to compromise piglet growth. However, new-born piglets transferred onto sows in late lactation experienced more competition at the udder, suggesting that the sows' stage of lactation is of importance to how achievable nurse sow strategies are. Thus, the two-step nurse sow strategy is likely the best option (in relation to growth and suckling behaviour), as it minimises the difference between piglet age and sow stage of lactation.
Mice express S and M opsins that form visual pigments for the detection of light and visual signaling in cones. Here, we show that
S opsin transcription is higher than that of
M opsin, which supports ...ultraviolet (UV) sensitivity greater than midwavelength sensitivity. Surprisingly, most cones coexpress both S and M opsins in a common cone cell type throughout the retina. All cones express M opsin, but the levels are graded from dorsal to ventral. The levels of S opsin are relatively constant. However, in the far dorsal retina, S opsin is repressed stochastically, such that some cones express M opsin only. These observations indicate that two different mechanisms control M and S opsin expression. We suggest that a common cone type is patterned across the retinal surface to produce phenotypic cone subtypes.
Background
Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, ...etiology, and symptoms in patients undergoing gastric emptying testing.
Methods
A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms.
Key Results
Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04).
Conclusions & Inferences
Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.
Wireless motility capsule (WMC) findings in suspected gastroparesis and relations to symptoms have been poorly defined. Evaluation of patients with gastroparesis symptoms revealed gastric emptying delays with WMCs that were similar to scintigraphy, were related to reduced contractility, and were often associated with extragastric or generalized transit delays; symptoms correlated poorly with WMC profiles. These findings provide insight into motor abnormalities in gastroparesis pathogenesis and form a basis for future investigations studying the impact of WMC testing on clinical care.
Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate ...nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received 18F-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.
Origami has been previously utilized in design to create deployable systems. Action origami, origami designed to move, has the ability to deploy to a larger state and have motion in the deployed ...state. The majority of action origami achieves motion through coupled systems of spherical mechanisms. An origami vertex, the point at which folds converge, is shown to be equivalent to a spherical change-point mechanism. A position analysis of an origami vertex is presented, resulting in a relationship between input and output angles as well as the path of the coupler link. A method for analyzing coupled systems of repeated spherical mechanisms is proposed and demonstrated using two examples. A better understanding of the kinematics of action origami increases the ability of designers to create compact, deployable mechanisms for use in packaging, space, and medical industries.
•An origami vertex is equivalent to a spherical change-point mechanism.•Most action origami achieves motion through coupled systems of spherical mechanisms.•The position analysis of an origami vertex includes output angle and coupler path.•A method for analyzing coupled systems of spherical mechanisms is proposed.•The results can help create compact, deployable mechanisms for application.
Animal migration is ubiquitous in nature with individuals within a population often exhibiting varying movement strategies. The basking shark (Cetorhinus maximus) is the world's second largest fish ...species, however, a comprehensive understanding of their long-term wider-ranging movements in the north-east Atlantic is currently lacking. Seventy satellite tags were deployed on basking sharks over four years (2012-2015) off the west coast of Scotland and the Isle of Man. Data from 28 satellite tags with attachment durations of over 165 days reveal post-summer ranging behaviours. Tagged sharks moved a median minimum straight-line distance of 3,633 km; achieving median displacement of 1,057 km from tagging locations. Tagged individuals exhibited one of three migration behaviours: remaining in waters of UK, Ireland and the Faroe Islands; migrating south to the Bay of Biscay or moving further south to waters off the Iberian Peninsula, and North Africa. Sharks used both continental shelf areas and oceanic habitats, primarily in the upper 50-200 m of the water column, spanning nine geo-political zones and the High Seas, demonstrating the need for multi-national cooperation in the management of this species across its range.
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