Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-range interactions in the lateral geniculate nucleus of the New-World monkey, Callithrix jacchus

Visual stimulation of zones extending beyond the classical receptive field can modulate the contrast gain of neurons in the lateral geniculate nucleus (LGN) of cats, but little is known about the effect of extra-classical visual stimulation on the LGN of primates. Hence, we compare the effect of long-range interactions in parvocellular and magnocellular LGN layers of the marmoset monkey Callithrix jacchus using optimal, incremental spots flashed on the classical receptive field either alone or simultaneously with the shift of a grating (98% contrast; 0.1 cycles/deg) confined to a peripheral annulus (radii: 5–15 deg). The contrast required to drive the response halfway to saturation (c50) of most LGN neurons was raised by remote pattern shifts. The c50 ratio [(shift+spot)/spot] in OFF-center magnocellular neurons was significantly higher than in OFF-center parvocellular neurons. OFF-center magnocellular neurons closer to the fovea (<10 deg eccentricity) tended to have a higher c50 ratio than in more peripheral neurons. A significant drop in visual sensitivity to 25% contrast spots was observed during remote motion: d′ fell from 1.8 to 1.4 in parvocellular neurons and from 2.2 to 1.7 in magnocellular neurons. Such long-range interactions produce a reduction in visual sensitivity by changing the gain of the geniculate relay and point to an inhibitory, motion-sensitive extra-classical receptive field in both parvocellular and magnocellular pathways, which may be involved in saccadic suppression and attentional mechanisms in early vision.
Tissue Engineering Models of Human Digits: Effect of Periosteum on Growth Plate Cartilage Development

Tissue-engineered middle phalanx constructs of human digits were investigated to determine whether periosteum wrapped partly about model midshafts mediated cartilage growth plate formation. Models were fabricated by suturing ends of polymer midshafts in a human middle phalanx shape with polymer sheets seeded with heterogeneous chondrocyte populations from bovine articular cartilage. Half of each midshaft length was wrapped with bovine periosteum. Constructs were cultured, implanted in nude mice for up to 20 weeks, harvested and treated histologically to assess morphology and cartilage proteoglycans. After 20 weeks of implantation, chondrocyte-seeded sheets adjacent to periosteum-wrapped midshaft halves established cartilage growth plates resembling normal tissue in vivo. Sheets adjacent to midshafts without periosteum had disorganized cells and no plate formation. Proteoglycans were present at both midshaft ends. Periosteum appears to guide chondrocytes toward growth plate cartilage organization and tissue engineering provides means for carefully examining construct development of this tissue.
Performance of processes of care and outcomes in patients with Staphylococcus aureus bacteremia.

BACKGROUND Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality in hospitalized adults. OBJECTIVE We aimed to identify current practice patterns in the management of SAB, and to evaluate their association with clinical outcomes. DESIGN Retrospective cohort study. SETTING A 1558-bed tertiary care teaching hospital. PATIENTS Adult patients hospitalized between January 1, 2012 through April 30, 2013, who had at least 1 positive blood culture with S aureus. INTERVENTION None MEASUREMENTS Electronic medical records were reviewed and the processes of care in the management of SAB were identified. The main outcome was clinical failure, defined as a composite endpoint of in-hospital mortality and persistent bacteremia. RESULTS Two hundred fifty episodes of SAB occurred in 241 patients, and 78 (32.4%) had clinical failure. Processes of care that impacted the risk of clinical failure included: timing of follow-up blood cultures (delays of >4 days had a relative risk [RR] of 6.6; 95% confidence interval [CI]: 2.1-20.5; P = 0.001), consultation with infectious diseases specialist within 6 days from diagnosis of SAB (RR: 0.3; 95% CI: 0.1-0.9; P = 0.03), and use of β-lactams in patients with methicillin-susceptible S aureus bacteremia (RR: 0.1; 95% CI: 0.04-0.5; P = 0.002). CONCLUSIONS The processes of care identified in our study could serve as quality and patient safety indicators for the management of SAB.
Attachment Status Affects Heart Rate Responses to Experimental Ostracism in Inpatients with Depression

Depression is assumed to be both a risk factor for rejection and a result of it, and as such constitutes an important factor in rejection research. Attachment theory has been applied to understand psychological disorders, such as depression, and can explain individual differences in responses to rejection. Research on autonomic nervous system activity to rejection experiences has been contradictory, with opposing strings of argumentation (activating vs. numbing). We investigated autonomic nervous system-mediated peripheral physiological responses (heart rate) to experimentally manipulated ostracism (Cyberball) in 97 depressed patients with organized (n = 52) and disorganized attachment status (n = 45). Controlling for baseline mean heart rate levels, depressed patients with disorganized attachment status responded to ostracism with significantly higher increases in heart rate than depressed patients with organized attachment status (p = .029; ηp2 = .051). These results suggest that attachment status may be a useful indicator of autonomic responses to perceived social threat, which in turn may affect the therapeutic process and the patient-therapist relationship.
SerpinB1 protects the mature neutrophil reserve in the bone marrow

SerpinB1 is among the most efficient inhibitors of neutrophil serine proteases—NE, CG, and PR‐3—and we investigated here its role in neutrophil development and homeostasis. We found that serpinB1 is expressed in all human bone marrow leukocytes, including stem and progenitor cells. Expression levels were highest in the neutrophil lineage and peaked at the promyelocyte stage, coincident with the production and packaging of the target proteases. Neutrophil numbers were decreased substantially in the bone marrow of serpinB1−/− mice. This cellular deficit was associated with an increase in serum G‐CSF levels. On induction of acute pulmonary injury, neutrophils were recruited to the lungs, causing the bone marrow reserve pool to be completely exhausted in serpinB1−/− mice. Numbers of myeloid progenitors were normal in serpinB1−/− bone marrow, coincident with the absence of target protease expression at these developmental stages. Maturation arrest of serpinB1−/− neutrophils was excluded by the normal CFU‐G growth in vitro and the normal expression in mature neutrophils of early and late differentiation markers. Normal absolute numbers of proliferating neutrophils and pulse‐chase kinetic studies in vivo showed that the bone marrow deficit in serpinB1−/− mice was largely restricted to mature, postmitotic neutrophils. Finally, upon overnight culture, apoptosis and necrosis were greater in purified bone marrow neutrophils from serpinB1−/− compared with WT mice. Collectively, these findings demonstrate that serpinB1 sustains a healthy neutrophil reserve that is required in acute immune responses.
Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity.

Ambient ozone (O3) levels are associated with cardiovascular morbidity and mortality, but the underlying pathophysiological mechanisms driving extrapulmonary toxicity remain unclear. This study examined the coronary vascular bed of rats in terms of constrictive and dilatory responses to known agonists following a single O3 inhalation exposure. In addition, serum from exposed rats was used in ex vivo preparations to examine whether bioactivity and toxic effects of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels exhibited greater basal tone and constricted to a greater degree to serotonin stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in coronary arteries from O3-exposed rats, compared with filtered air-exposed controls. Dilation to ACh was restored by combined superoxide dismutase and catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum from exposed rats was perfused into the lumen of coronary arteries from unexposed, naïve rats, the O3-induced reduction in vasodilatory response to ACh was partially recapitulated. Furthermore, following O3 inhalation, serum exhibited a nitric oxide scavenging capacity, which may partially explain blunted ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures may be due to compositional changes of the circulation. These studies shed light on possible mechanisms of action that may explain O3-associated cardiac morbidity and mortality in humans.
Labor Supply Estimation Biases from Disregarding Nonwage Benefits

Labor supply models and research underpinned by labor supply decisions often assume that workers' choices are functions of wage and wage offers. However, the literature shows evidence that such decisions at least partly depend on nonwage benefits encompassed in jobs and occupations. In this paper, I develop and estimate a stochastic dynamic model of occupation and job choice, where nonwage benefits are directly incorporated into the decision alongside wages (a full model). Nested within the full model is a wage model, which represents the common practice in the literature of basing selection solely on wages and disregarding nonwage benefits. I separately estimate the full model and the nested wage model to compare the implications (biases) of omitting nonwage benefits. I compare the two models' estimates of elasticities and an inequality reduction intervention policy. I find that disregarding nonwage benefits generally causes biases. There are cases when the two models predict very similar outcomes and have close estimates, such as in occupation&#8208;specific elasticities and job transition elasticities. But these special cases are products of canceling biases. In most cases, ignoring nonwage benefits will bias estimates by overestimating the importance of wage in the selection process and by disregarding changes in relative prices between wage and nonwage benefits.
Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

1 The effect of sodium valproate (VPA; 500 mg thrice daily for 7 days) and matched placebo on the disposition and psychomotor profile of a single dose of carbamazepine (CBZ; 10 mg kg-1) was studied in eight healthy male subjects using a randomised balanced crossover design. 2 VPA alone had no effect on antipyrine clearance, urinary 6 beta-hydroxycortisol excretion and a battery of psychomotor function tests after 3 days' treatment despite achieving a mean steady-state concentration (90 +/- 6 mg 1(-1)) well within the target range (50-100 mg 1(-1)) for the drug. 3 VPA pre-treatment did not alter total CBZ area under the concentration-time curve (AUC 0-59 h) but did prolong CBZ elimination half life by 12% (P less than 0.01). AUC 0-59 h for free plasma CBZ was 13% higher (P less than 0.02) and half-life of unbound CBZ 16% longer (P less than 0.02) during VPA treatment. CBZ-10,11 epoxide (CBZ-E) levels (52%) and CBZ-E/CBZ ratios (45%) were both elevated by concurrent VPA (P less than 0.05) and free CBZ fraction was increased by 7% (P less than 0.02). 4 The sole effect of VPA on the psychomotor profile of CBZ was prolongation of card sorting time (P less than 0.05), although CBZ-related side effects were reported as more severe when VPA was also taken (P less than 0.01). 5 These data suggest that VPA displaces CBZ from plasma protein binding sites and inhibits the metabolism of both the parent drug and its epoxide. (ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone

The neurosteroid allopregnanolone is a potent and efficacious modulator of γ-aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 μg in 5 μl) on basal and stress-induced changes in the extracellular concentrations of dopamine were investigated by microdialysis in various brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 μg in 5 μl). Allopregnanolone reduced (by a maximum of 65 to 75%) basal dopamine content in the prefrontal cortex and nucleus accumbens in a dose-dependent manner, but had no effect on dopamine output in the striatum. Allopregnanolone (10 to 15 μg) also completely prevented the increase in extracellular dopamine concentrations in the nucleus accumbens and cerebral cortex induced by foot-shock stress. Midazolam reduced basal dopamine content in all three brain regions studied as well as the stress- induced increase in dopamine content in the nucleus accumbens and cerebral cortex with a greater potency than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of dopaminergic transmission in the rat cerebral cortex and nucleus accumbens, two brain areas which are important in the regulation of emotional processes. These agents do not appear to affect striatal dopaminergic transmission which modulates motor function.
Rebuilding Local Government Finances After Conflict: Lessons from a Property Tax Reform Programme in Post-Conflict Sierra Leone

ABSTRACT This research interrogates the factors underpinning the relative success of a property tax reform programme in Sierra Leone. Recognising the importance of politics in shaping reform outcomes, it highlights reform strategies that have contributed to overcoming both technical and political barriers to reform. It highlights three interconnected arguments. First, there is a need for long-term, hands-on, local partnerships that support local capacity, help to confront political resistance and build a constituency for reform. Second, there should be expanded focus on politically contentious efforts to strengthen transparency, public outreach, and enforcement among elites, as they are critical to programme success and sustainability. Third, a focus on the same politically contentious elements of reform can help external actors better assess the extent of local political commitment to reform early-on, and thus target reform funding and efforts more effectively.
Dry etching and sputtering

Dry etching is an important process for micro– and nanofabrication. Sputtering effects can arise in two contexts within a dry–etch process. Incoming ions cause removal of volatile products that arise from the interaction between the dry–etch plasma and the surface to be etched. Also, the momentum transfer of an incoming ion can cause direct removal of the material to be etched, which is undesirable as it can cause electrical or optical damage to the underlying material. This is largely avoided in dry–etch processes by use of reactive chemistries, although in some processes this component of the etching can be significant. Etch processes, both machine type and possible etch chemistries, are reviewed. Methods of characterizing the electrical and optical damage related to ion impact at the substrate are described. The use of highly reactive chemistries and molecular constituents within the plasma is best for reducing the effects of damage.
Quality use of medicines in residential aged care.

BACKGROUND Older people are more likely to be exposed to polypharmacy. People with dementia, especially those living in residential aged care facilities (RACFs), are at particularly high risk of medication harm. We sought to describe medications prescribed for a sample of people with dementia living in RACFs. METHODS A total of 351 residents with dementia aged over 65 years were recruited from 36 RACFs in Western Australia. Data on all medications prescribed were collected, including conventional medications, herbal medications, vitamins and minerals. RESULTS Polypharmacy was identified in 91.2% (average 9.75 medications per person); one-third were prescribed an antipsychotic medication; and 50.4% were found to be taking at least one potentially inappropriate medication. The combination of antipsychotics and antidepressants was the most frequently observed drug-drug interaction, being prescribed to 15.7% of participants. DISCUSSION People with dementia living in RACFs are commonly exposed to polypharmacy. Prescription of contraindicated medications, antipsychotics, medications with high anticholinergic burden, and combinations of potentially inappropriate medications is also common. There may be substantial scope to improve prescribing for older people with dementia living in RACFs.
Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.
Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy.

PURPOSE Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. This study was designed to evaluate whether TOP2A gene alterations may predict incremental responsiveness to anthracyclines in some breast cancers. METHODS A total of 4,943 breast cancers were analyzed for alterations in TOP2A and HER2. Primary tumor tissues from patients with metastatic breast cancer treated in a trial of chemotherapy plus/minus trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test set followed by evaluation of malignancies from two separate, large trials for changes in these same genes as a validation set. Association between these alterations and clinical outcomes was determined. RESULTS Test set cases containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC) plus trastuzumab, demonstrated longer progression-free survival compared to those treated with AC alone (P = .0002). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar improvement in survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in a larger validation set, where HER2/TOP2A coamplification was again associated with longer survival when only anthracycline-containing chemotherapy was used for treatment compared with outcome in HER2-positive cancers lacking TOP2A coamplification. CONCLUSION In a study involving nearly 5,000 breast malignancies, both test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of an incremental response to anthracycline-based chemotherapy. Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy advantage for breast cancers than previously thought.
Endolithic algae: an alternative source of photoassimilates during coral bleaching

Recent reports of worldwide coral bleaching events leading to devastating coral mortality have caused alarm among scientists and resource managers. Differential survival of coral species through bleaching events has been widely documented. We suggest that among the possible factors contributing to survival of coral species during such events are endolithic algae harboured in their skeleton, providing an alternative source of energy. We studied the dynamics of photosynthetic pigment concentrations and biomass of endoliths in the skeleton of the encrusting coral Oculina patagonica throughout a bleaching event. During repeated summer bleaching events these endolithic algae receive increased photosynthetically active radiation, increase markedly in biomass, and produce increasing amounts of photoassimilates, which are translocated to the coral. Chlorophyll concentrations and biomass of endoliths were 4.6 ± 1.57 and 1570 ± 427 μg cm−2 respectively, in skeletons of relatively healthy colonies (0–40%bleaching) but up to 14.8± 2.5 and 4036 ± 764 g cm−2 endolith chlorophyll and biomass respectively, in skeletons of bleached colonies (greater than 40% bleaching). The translocation dynamics of 14C–labelled photoassimilates from the endoliths to bleached coral tissue showed significantly higher 14C activity of the endoliths harboured within the skeletons of bleached corals than that of the endoliths in non–bleached corals. This alternative source of energy may be vital for the survivorship of O. patagonica, allowing gradual recruitment of zooxanthellae and subsequent recovery during the following winter.
Personal recommender systems for learners in lifelong learning networks: the requirements, techniques and model

This article argues that there is a need for Personal Recommender Systems (PRSs) in Learning Networks (LNs) in order to provide learners with advice on the suitable learning activities to follow. LNs target lifelong learners in any learning situation, at all educational levels and in all national contexts. They are community-driven because every member is able to contribute to the learning material. Existing Recommender Systems (RS) and recommendation techniques used for consumer products and other contexts are assessed on their suitability for providing navigational support in an LN. The similarities and differences are translated into specific requirements for learning and specific requirements for recommendation techniques. The article focuses on the use of memory-based recommendation techniques, which calculate recommendations based on the current data set. We propose a combination of memory-based recommendation techniques that appear suitable to realise personalised recommendation on learning activities in the context of e-learning. An initial model for the design of such systems in LNs and a roadmap for their further development are presented.