Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read ...mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.
This meeting covered the range of cosmic explosions from solar flares to
gamma-ray bursts. A common theme is the role of rotation and magnetic fields. A
rigorous examination is underway to ...characterize systematic effects that might
alter the Type Ia supernova results suggesting an accelerating Universe. The
discovery of the central point of X-ray emission in Cas A by CXO should give
new insight into the core collapse problem in general and the nature of the
still undetected compact remnant in SN 1987A in particular. Jets were described
from protostars to microquasars to blazars to gamma-ray bursts. Polarization
studies of core-collapse supernovae lead to the conclusion that core collapse
is not merely asymmetric, but strongly bi-polar. To account for normal
core-collapse supernovae, the explosion must be jet-like in routine
circumstances, that is, in the formation of neutron stars, not only for black
holes. Given the observed asymmetries, estimates of explosion energies based on
spherically-symmetric models must be regarded with caution. The strong
possibility that at least some gamma-ray bursts arise from massive stars means
that it is no longer possible to decouple models of the gamma-ray burst and
afterglow from considerations of the "machine." The implied correlation of
gamma-ray bursts with star formation and massive stars and evidence for jets
does not distinguish a black hole collapsar model from models based on the
birth of a magnetar. Calorimetry of at least one afterglow suggests that
gamma-ray bursts cannot involve highly inefficient internal shock models.
Essentally all gamma-ray burst models involve the "Blandford Anxiety," the
origin of nearly equipartition magnetic fields in the associated relativistic
shocks.
The allowed range of progenitor structures for SN 1987A is shown to be a narrow corridor in the parameter space of envelope mass M(env), and helium enrichment Y. The principle constraints adopted ...from evolutionary studies are that the hydrogen burning shell be extinct and that the helium burning shell be active. Assuming hydrostatic and thermal equilibrium in the structure beyond the helium burning shell, the progenitor structure of SN 1987A is constrained by determining the parameters which are consistent with the observed properties of SK -69, 202 deg. Self-consistency requires that the radius of the helium core or the location of the helium burning shell or both vary with envelope mass and composition even at fixed luminosity, core mass, and stellar radius. 13 refs.
This is the text of a summary of the workshop on asymmetric explosions held in Austin in June, 2003. A brief review is given of the author's own interests in dynamo theory as it may apply in the core ...collapse ambience. Of particular interest are saturation fields for the cases with central neutron stars and black holes and the possibility of driving MHD jets with the resulting fields. Interesting physics that may arise with large fields such as effects on the equation of state to produce anisotropic pressure and effects on neutrino cross sections and transport are briefly outlined. A brief summary of the contributions to the workshop is then given with special credit to Scratchy Serapkin. Of special note were the summaries of the advances due to spectropolarimetry in revealing the asymmetric nature of supernovae. Major progress in understanding the binary progenitors and explosion physics of Type Ia was presented. Other talks entwined the nature of asymmetric core collapse, gamma-ray bursts and "hypernovae." My final charge to the attendees was "Go thee forth and think about rotation and magnetic fields!"
This is the text of an introduction to a workshop on asymmetric explosions held in Austin in June, 2003. The great progress in supernova research over thirty-odd years is briefly reviewed. The ...context in which the meeting was called is then summarized. The theoretical success of the intrinsically multidimensional delayed detonation paradigm in explaining the nature of Type Ia supernovae coupled with new techniques of observations in the near IR and with spectropolarimetry promise great advances in understanding binary progenitors, the explosion physics, and the ever more accurate application to cosmology. Spectropolarimetry has also revealed the strongly asymmetric nature of core collapse and given valuable perspectives on the supernova - gamma-ray burst connection. The capability of the magneto-rotational instability to rapidly create strong toroidal magnetic fields in the core collapse ambiance is outlined. This physics may be the precursor to driving MHD jets that play a role in asymmetric supernovae. Welcome to the brave new world of three-dimensional explosions!
Purpose
Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for ...out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA
1c
has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group.
Methods
A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7–25 years with T1D, a current HbA
1c
≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA
1c
between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes.
Conclusion
This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden.
Trial registration
This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).
The energy consumption of modern belt conveying systems has reduced considerably over the past few decades. Although extensive research has been conducted into the production of energy-efficient belt ...conveyors, significant scope remains to further reduce the energy consumption, especially when heavily loaded or long overland belt conveyors are considered. A new rail-based conveyor system has been developed to reduce the energy consumption of heavily loaded and long overland conveyors. The new technology is aptly named the Rail Conveyor due to its combination of two well-established transportation technologies. The Rail Conveyor merges the benefits of both belt conveyor technology and rail transport to produce an energy-efficient and cost-effective bulk material transportation system. This paper presents a comparison between the energy consumption and motion resistances of the Rail Conveyor system and conventional belt conveyors. The Rail Conveyor is a continuous bulk material transportation system that, due to track wheels running on steel rails, shares a rolling resistance similar in magnitude to railway systems. Due to the effective elimination of the indentation rolling resistance and belt and bulk material flexure resistance within the Rail Conveyor system, an approximate reduction of 50% in energy consumption can be achieved when compared to conventional belt conveyors.
There are hints that nearby Type Ia supernovae may be a little different than
those at large redshift. Confidence in the conclusion that there is a
cosmological constant and an accelerating Universe ...thus still requires the hard
work of sorting out potential systematic effects. Polarization data show that
core-collapse supernovae (Type II and Ib/c) probably depart strongly from
spherical symmetry. Evidence for exceedingly energetic supernovae must be
considered self-consistently with evidence that they are asymmetric, a
condition that affects energy estimates. Jets arising near the compact object
can produce such asymmetries. There is growing conviction that gamma-ray bursts
intrinsically involve collimated or jet-like flow and hence that they are also
strongly asymmetric. SN 1998bw is a potential rosetta stone that will help to
sort out the physics of explosive events. Are events like SN 1998bw more
closely related to "ordinary" supernovae or "hypernovae?" Do they leave behind
neutron stars as "ordinary" pulsars or "magnetars" or is the remnant a black
hole? Are any of these events associated with classic cosmic gamma-ray bursts
as suggested by the supernova-like modulation of the afterglows of GRB 970228,
GRB 980326 and GRB 990712?
Background:
Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group.
Methods:
...Patients were randomly assigned in a 2 × 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo.
Results:
Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level ≥ 1.7 mg/dL ≥150 μmol/L, 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients 2% versus placebo, 6 of 223 patients 3%;
P = not significant NS), although there was a 3-fold excess of minor bleeds (34 of 225 15% versus 12 of 223 patients 5%;
P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 4% versus 6 of 188 patients 3%;
P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients 34% versus 56 of 188 patients 30%;
P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL 4.22 mmol/L versus placebo, 196 mg/dL 5.08 mmol/L;
P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL 2.31 mmol/L versus 114 mg/dL 2.96 mmol/L;
P < 0.0001), and triglyceride levels by 13% (166 mg/dL 1.87 mmol/L versus 186 mg/dL 2.10 mmol/L;
P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase;
P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels.
Conclusion:
During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.
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