While the standard model of particle physics does not include free particles with fractional charge, experimental searches have not ruled out their existence. We report results from the Cryogenic ...Dark Matter Search (CDMS II) experiment that give the first direct-detection limits for cosmogenically produced relativistic particles with electric charge lower than e/6. A search for tracks in the six stacked detectors of each of two of the CDMS II towers finds no candidates, thereby excluding new parameter space for particles with electric charges between e/6 and e/200.
This volume presents collected essays of Gary N. Knoppers (1956-2018) on the historical books of the Hebrew Bible, among them seven thoroughly revised and eight newly published ones. An introduction ...by H.G.M. Williamson acknowledges their significance for Knoppers' oeuvre.
•Almost half of GABA in cochlear nucleus regions may be in centrifugal innervation.•Most GABAergic centrifugal pathways reach the cochlear nucleus via the trapezoid body.•Lesion of centrifugal ...pathways results in decreased cochlear nucleus aspartate levels.•Lesion of centrifugal pathways results in decreased cochlear nucleus glutamate levels.•Lesion of centrifugal pathways results in increased cochlear nucleus taurine levels.
There is evidence for glutamate, γ-amino butyric acid (GABA), and glycine as neurotransmitters of centrifugal pathways to the cochlear nucleus, but the quantitative extent of their contributions to amino acid neurotransmission in cochlear nucleus regions has not been known. We used microdissection of freeze-dried tissue sections of rat cochlear nucleus, with mapping of sample locations, combined with a high performance liquid chromatography (HPLC) assay, to measure amino acid levels in cochlear nucleus subregions of rats with unilateral lesions of centrifugal pathways to the cochlear nucleus. In rats with lesions transecting all or almost all pathways to the cochlear nucleus from brain stem regions, GABA, aspartate, and glutamate levels were reduced, compared to contralateral values, in almost all ipsilateral cochlear nucleus regions. The largest reductions, in dorsal (DCN), anteroventral (AVCN), and posteroventral (PVCN) cochlear nucleus regions, approached 50% for GABA, 40% for aspartate, and 30% for glutamate. In contrast, glutamine and taurine levels were typically higher in lesioned-side cochlear nucleus regions than contralaterally. Effects on glycine levels were mixed but usually included increased lesioned-side values compared to contralateral, probably reflecting a balance between increases during protein breakdown and decreases of free glycine in transected pathways. More limited lesions transecting just dorsal pathways showed much less effect on amino acid levels. Lesion of the ipsilateral trapezoid body connection plus ipsilateral superior olivary nuclei resulted in decreases of GABA, aspartate, and glutamate levels especially in ventral cochlear nucleus regions. No clear contralateral effects of this lesion could be shown. The results most strongly support centrifugal GABAergic pathways to the cochlear nucleus, providing almost half of GABAergic neurotransmission in most regions. Our results support and extend previously published measurements of lesion effects on GABA uptake and release in cochlear nucleus subdivisions.
Current high-throughput screening assay optimization is often a manual and time-consuming process, even when utilizing design-of-experiment approaches. A cross-platform, Cloud-based Bayesian ...optimization-based algorithm was developed as part of the National Center for Advancing Translational Sciences (NCATS) ASPIRE (A Specialized Platform for Innovative Research Exploration) Initiative to accelerate preclinical drug discovery. A cell-free assay for papain enzymatic activity was used as proof of concept for biological assay development and system operationalization. Compared with a brute-force approach that sequentially tested all 294 assay conditions to find the global optimum, the Bayesian optimization algorithm could find suitable conditions for optimal assay performance by testing 21 assay conditions on average, with up to 20 conditions being tested simultaneously, as confirmed by repeated simulation. The algorithm could achieve a sevenfold reduction in costs for lab supplies and high-throughput experimentation runtime, all while being controlled from a remote site through a secure connection. Based on this proof of concept, this technology is expected to be applied to more complex biological assays and automated chemistry reaction screening at NCATS, and should be transferable to other institutions.
Root competition inhibits root proliferation. All else equal, a plant should invest roots in a nutrient patch devoid of roots rather than one already occupied by roots. Less clear is how a plant ...should respond to intra-plant versus inter-plant root competition. We consider three responses for how a plant may select habitats based on intra-versus inter-plant root competition: inter-plant avoidance, resource matching, or intra-plant avoidance. The first assumes that plants prefer to have their own space and preferentially proliferate roots away from neighboring plants. The second response, based on the ideal free distribution, assumes that plants invest so as to equalize average returns from roots, regardless of the identity of the neighboring roots. The third, based on game theory, assumes that the plant proliferates roots so as to maximize whole-plant fitness, in which case it is better to proliferate plants among a neighbor's roots than to continue proliferating amongst one's own roots. To test among these models we grew beans (Phaseolus varigaris, var, Kenya) in a greenhouse under two planting scenarios. Both scenario were tested under 0.5 and 0.1 strength of nutrient solution. Under scenario A (fence-sitters), two split-root plants each shared two patches by virtue of having roots in each. Under scenario B (owners) two plants each had their own patch. The results supported the game theory model of intra-plant avoidance (whole plant habitat selection). Fence-sitters produced 150% more root mass per individual than owners. Owners produced 90% more yield (dry mass of pods) than fence-sitters. Furthermore, owners had significantly higher shoot-root ratios than fence-sitters. These effects did not vary with high or low nutrient levels. The over-proliferation of roots under inter-plant competition (fence-sitters) was manifest by the tenth day after planting. In short, the fence-sitters engaged in a tragedy of the commons in which they competed with each other through root proliferation. At the ESS, the fitness maximizing strategy of the individual is to sacrifice collective yield in a quest to 'steal' nutrients from its neighbor. The research has three implications. First, plants may be able to assess and respond to local opportunities in a manner that maximizes the good of the whole plant. Second, nutrient foraging as a game may provide a fresh perceptive for viewing root competition either intra-specifically or inter-specifically. Third, it may be possible to increase the yield of certain crop species by breeding more 'docile' cultivars that do not overproduce roots in response to inter-plant competition.
Decisions to limit life-sustaining therapy (DLLST) in the ICU are used to uphold patients' autonomy, protect them from non-beneficial treatment and fairly distribute resources. The institution of ...these decisions is complex, with a variety of qualitative and quantitative data published. This review aims to summarize the main issues and review the contemporary research findings on this subject.
DLLST are used in a variety of clinical and non-clinical situations, before and after ICU admission, and are not always part of end-of-life management. There are many dilemmas and barriers that beset their institution. Many ICU physicians feel inadequately trained to carry them out and they are frequently a source of conflict. A variety of strategies have been examined to improve their institution, including advanced directives, intensive communication strategies and family information leaflets, many of which have improved patient and family-centred outcomes.
There are a number of uncertainties that beset the institution of DLLST in the ICU; however, a variety of research has improved our ability to understand and implement them. This review frames some of the dilemmas and discusses some of the procedural strategies that have been used to improve outcomes.
PURPOSE:The purpose of this study is to evaluate the use of micropulse transscleral cyclophotocoagulation (MP-TSCPC), a new and increasingly popular treatment, in patients with uncontrolled glaucoma.
...METHODS:A retrospective chart review was performed for all patients who underwent a MP-TSCPC at the Glaucoma Associates of Texas.
RESULTS:A total of 84 eyes were treated with MP-TSCPC in this study with a mean follow-up time of 4.3 months. The mean age of treated patients was 74 years and 48 (57%) were female. Preoperatively, mean intraocular pressure (IOP) was 27.7 mm Hg and mean number of ocular antihypertensive medications used was 3.3. Mean postoperative IOP at months 1, 3, 6, and 12 were lowered to 16.3 mm Hg (41.2% reduction), 14.6, 13.0, and 11.1 mm Hg, respectively. Postoperative ocular antihypertensive medication use was also lowered to 1.9, 2.0, 2.0, and 2.3 medications at months 1, 3, 6, and 12, respectively. Five patients required further laser or surgical intervention for adequate IOP control. Complications included hypotony, IOP spike, hyphema, serous choroidal detachment, persistent inflammation, and vision loss. At 3 months, inflammation was still present in 46% of eyes and vision loss of at least 1 line was present in 41% of eyes.
CONCLUSIONS:MP-TSCPC is effective at lowering IOP and decreasing the need for ocular antihypertensive medications. Eyes with limited visual potential or at high risk for incisional glaucoma surgery can successfully be treated with MP-TSCPC as a reasonable and effective alternative to traditional CPC. These results present short-term data and both longer follow-up and further studies are necessary.
PURPOSE:To report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with prior incisional glaucoma surgery.
PATIENTS AND METHODS:A retrospective review was performed for ...all patients who underwent a GATT procedure with a history of prior incisional glaucoma surgery.
RESULTS:Thirty-five eyes of 35 patients were treated. The mean age was 67.7 years. Nineteen eyes had a prior trabeculectomy, 13 eyes had a prior glaucoma drainage device, 4 eyes had a prior trabectome, and 5 eyes had prior endocyclophotocoagulation. Mean follow-up time was 22.7 months. For all eyes, the mean preoperative intraocular pressure (IOP) (SD) was 25.7 (6.5) mm Hg on 3.2 (1.0) glaucoma medications and at 24 months, the mean IOP (SD) was 15.4 (4.9) mm Hg on 2.0 (1.4) glaucoma medications (P<0.001). The prior trabeculectomy group had a preoperative IOP (SD) of 24.6 (6.4) mm Hg on 3.2 (1.0) medications and at month 24, the mean IOP (SD) was 16.7 (5.6) mm Hg on 2.1 (1.4) glaucoma medications. In the prior glaucoma drainage device group, the mean preoperative IOP (SD) was 27.0 (7.1) mm Hg on 3.4 (1.1) glaucoma medications and at 24 months, the mean IOP (SD) was 12.9 (2.6) mm Hg on 2.1 (1.2) glaucoma medications. At 24 months, the cumulative proportion of failure was 0.4 and the cumulative proportion of reoperation was 0.29.
CONCLUSIONS:GATT appears to be safe and successful in treating 60% to 70% of open-angle patients with prior incisional glaucoma surgery. When considering all eyes, there was a significant decrease in IOP and required glaucoma medications at 24 months. This surgery should be considered in certain patients with open angles who have failed a primary traditional glaucoma surgery.
There is a need for tests that are derived from the ordinary least squares (OLS) estimators of regression coefficients and are useful in the presence of unspecified forms of heteroskedasticity and ...autocorrelation. A method that uses the moving block bootstrap and quasi‐estimators in order to derive a consistent estimator of the asymptotic covariance matrix for the OLS estimators and robust significance tests is proposed. The method is shown to be asymptotically valid and Monte Carlo evidence indicates that it is capable of providing good control of significance levels in finite samples and good power compared with two other bootstrap tests.
This article ascertains the underlying causes of the persistence of unsustainable settlement patterns and trends in post-apartheid South Africa. Despite positive development planning policy ...intentions in the post-apartheid South Africa, glaring deprivation and spatial inequality has persisted. The article is grounded in a chronological analysis of demographic, functional and regional economic dynamics at the different epochs of South Africa's history as well as the settlement policy and planning intentions. Its main finding is that the persistence of unsustainable settlement patterns and trends in post-apartheid South Africa is largely a result of misplaced settlement policies and strategies. They give knee-jerk responses to global, regional, national and local dynamics shaping settlement patterns and trends. The recommendation is that development planning initiatives should be informed by the dialectics of settlement facets at local, regional, national and global levels for them to deal decisively with the historical problem of unsustainable patterns and trends.
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