Comparison of Outcomes in Level I vs Level II Trauma Centers in Patients Undergoing Craniotomy or Craniectomy for Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) carries a devastatingly high rate of morbidity and mortality. OBJECTIVE: To assess whether patients undergoing craniotomy/craniectomy for severe TBI fare better at level I than level II trauma centers in a mature trauma system. METHODS: The data were extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients \u3e 18 yr with severe TBI (Glasgow Coma Scale [GCS] score less than 9) undergoing craniotomy or craniectomy in the state of Pennsylvania from January 1, 2002 through September 30, 2017. RESULTS: Of 3980 patients, 2568 (64.5%) were treated at level I trauma centers and 1412 (35.5%) at level II centers. Baseline characteristics were similar between the 2 groups except for significantly worse GCS scores at admission in level I centers (P = .002). The rate of in-hospital mortality was 37.6% in level I centers vs 40.4% in level II centers (P = .08). Mean Functional Independence Measure (FIM) scores at discharge were significantly higher in level I (10.9 ± 5.5) than level II centers (9.8 ± 5.3; P \u3c .005). In multivariate analysis, treatment at level II trauma centers was significantly associated with in-hospital mortality (odds ratio, 1.2; 95% confidence interval, 1.03-1.37; P = .01) and worse FIM scores (odds ratio, 1.4; 95% confidence interval, 1.1-1.7; P = .001). Mean hospital and ICU length of stay were significantly longer in level I centers (P \u3c .005). CONCLUSION: This study showed superior functional outcomes and lower mortality rates in patients undergoing a neurosurgical procedure for severe TBI in level I trauma centers

Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association with increasing amyloid-β and tau pathology

BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer’s disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1–7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity. METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. RESULTS: ACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = −0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating  conversion of Ang II to Ang (1–7)) is reduced in AD. CONCLUSIONS: Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0217-7) contains supplementary material, which is available to authorized users

Modelling dependency networks to inform data structures in BIM and smart cities

The pervasive deployment of "smart city" and "smart building" projects in cities world-wide is driving innovation on many fronts including; technology, telematics, engineering and entrepreneurship. This paper focuses on the technical and engineering perspectives of BIM and smart cities, by extending building and urban morphology studies as to respond to the challenges posed by Big Data, and smart infrastructure. The proposed framework incorporates theoretical and modelling descriptions to verify how network-based models can act as the backbone skeletal representation of both building and urban complexity, and yet relate to environmental performance and smart infrastructure. The paper provides some empirical basis to support data information models through building dependency networks as to represent the relationships between different existing and smart infrastructure components. These dependency networks are thought to inform decisions on how to represent building and urban data sets in response to different social and environmental performance requirements, feeding that into void and solid descriptions of data maturity models. It is concluded that network-based models are fundamental to comprehend and represent the complexity of cities and inform urban design and public policy practices, in the design and operation phases of infrastructure projects

Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468). RESULTS: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease. CONCLUSIONS: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML

Silicon-Organic Hybrid (SOH) and Plasmonic-Organic Hybrid (POH) integration

Silicon photonics offers tremendous potential for inexpensive high-yield photonic-electronic integration. Besides conventional dielectric waveguides, plasmonic structures can also be efficiently realized on the silicon photonic platform, reducing device footprint by more than an order of magnitude. However, nei-ther silicon nor metals exhibit appreciable second-order optical nonlinearities, thereby making efficient electro-optic modulators challenging to realize. These deficiencies can be overcome by the concepts of silicon-organic hybrid (SOH) and plasmonic-organic hybrid integration, which combine SOI waveguides and plasmonic nanostructures with organic electro-optic cladding materials

Oxalate and Phytate of Soy Foods

The consumption of foods made from soybeans is increasing because of their desirable nutritional value. However, some soy foods contain high concentrations of oxalate and/or phytate. Oxalate is a component of calcium oxalate kidney stones, whereas phytate is an inhibitor of calcium kidney stone formation. Thirty tested commercial soy foods exhibited ranges of 0.02−2.06 mg oxalate/g and 0.80−18.79 mg phytate/g. Commercial soy foods contained 2−58 mg of total oxalate per serving and 76−528 mg phytate per serving. Eighteen of 19 tofu brands and two soymilk brands contained less than 10 mg oxalate per serving, defined as a low oxalate food. Soy flour, textured vegetable soy protein, vegetable soybeans, soy nuts, tempeh, and soynut butter exhibited greater than 10 mg per serving. The correlation between oxalate and phytate in the soy foods was significant (r = 0.71, P \u3c 0.001) indicating that oxalate-rich soy foods also contain higher concentrations of phytate. There also was a significant correlation, based on molar basis, between the divalent ion binding potential of oxalate plus phytate and calcium plus magnesium (r = 0.90, P \u3c 0.001) in soy foods. Soy foods containing small concentrations of oxalate and moderate concentrations of phytate may be advantageous for kidney stone patients or persons with a high risk of kidney stones

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Silicon-Organic Hybrid (SOH) and Plasmonic-Organic Hybrid (POH) integration

Silicon-organic hybrid (SOH) and plasmonic-organic hybrid (POH) integration combines organic clectro-optic materials with silicon photonic and plasmonic waveguides, The concept enables fast and power-efficient modulators that support advanced modulation formats such as QPSK and 16QAM

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio