Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a ...multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse.
A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further.
Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively.
Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.
A PowerPC system-on-a-chip processor which makes use of dynamic voltage scaling and on-the-fly frequency scaling to adapt to the dynamically changing performance demands and power consumption ...constraints of high-content, battery powered applications is described. The PowerPC core and caches achieve frequencies as high as 380 MHz at a supply of 1.8 V and active power consumption as low as 53 mW at a supply of 1.0 V. The system executes up to 500 MIPS and can achieve standby power as low as 54 /spl mu/W. Logic supply changes as fast as 10 mV//spl mu/s are supported. A low-voltage PLL supplied by an on-chip regulator, which isolates the clock generator from the variable logic supply, allows the SOC to operate continuously while the logic supply voltage is modified. Hardware accelerators for speech recognition, instruction-stream decompression and cryptography are included in the SOC. The SOC occupies 36 mm/sup 2/ in a 0.18 /spl mu/m, 1.8 V nominal supply, bulk CMOS process.
A 10nm logic platform technology is presented for low power and high performance application with the tightest contacted poly pitch (CPP) of 64nm and metallization pitch of 48nm ever reported in the ...FinFET technology on both bulk and SOI substrate. A 0.053um 2 SRAM bit-cell is reported with a corresponding Static Noise Margin (SNM) of 140mV at 0.75V. Intensive multi-patterning technology and various self-aligned processes have been developed with 193i lithography to overcome optical patterning limit. Multi-workfunction (WF) gate stack has been enabled to provide Vt tunability without the variability degradation induced by channel dopants.
We demonstrate, for the first time, Vertical-Transport Nanosheet (VTFET) CMOS logic transistors at sub-45nm gate pitch on bulk silicon wafers. We show that VTFETs present an opportunity to break the ...Contacted Gate Pitch (CGP) barrier faced by Lateral-Transport FETs. VTFETs offer scaling relief for electrostatics and parasitics by decoupling key device features from CGP-scaling roadblocks. First, nMOS/pMOS VTFET electrostatics are reported at sub-45nm gate pitch with \text{SS} = 69/68\ \text{mV}/\text{dec} and sub-30mV DIBL. Well-behaved short channel characteristics with Si/SiGe source and drain are demonstrated in hardware. Symmetric device characteristics for SS and DIBL are achieved (with process optimization). Vertical nanosheets are utilized rather than vertical nanowires 1, 2 for improved performance and area scaling. Functional ring oscillators demonstrate the excellent effective capacitance (Ceff) scaling advantages of VTFET nanosheets. Logic area scaling is furthered by use of Zero Diffusion Break (ZDB) isolation to eliminate dummy gates. Innovative I/O FET device design and hardware characteristics are shared.
Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying neurons do not pass the G1/S-phase checkpoint to resume ...DNA synthesis. The specific factors that trigger abortive DNA synthesis are not characterized. Here we show that the combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia, the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2 activity and phosphorylation of the retinoblastoma protein. This contrasts to kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL-positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle transition. These findings suggest that hypoxia-ischemia triggers neurons to reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain. Our data also suggest that the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers. Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis.
Background and purpose: The manipulation of tumour blood supply and thus oxygenation is a potentially important strategy for improving the treatment of solid tumours by radiation. Increased knowledge ...about the characteristics that distinguish the tumour vasculature from its normal counterparts may enable tumour blood flow to be more selectively modified. Nicotinamide (NA) causes relaxation of preconstricted normal and tumour-supply arteries in rats. It has also been shown to affect microregional blood flow in human tumours. Direct effects of NA on human tumour supply arteries have not previously been reported. This paper describes our evaluation of the effects of NA on two parameters: ‘spontaneous’, oscillatory contractile activity and agonist (phenylephrine)-induced constriction in the arteries supplying human renal cell carcinomas.
Materials and methods: Isolated renal cell carcinoma feeder vessels were perfused in an organ bath with the α
1-adrenoceptor agonist phenylephrine (PE). When the arteries had reached a plateau of constriction, nicotinamide (8.2 mM) was added to the perfusate and changes in perfusion pressure were measured.
Results: PE (10 μM) induced a sustained constriction in the majority of the renal cell carcinoma feeder vessels examined, demonstrating that they retain contractile characteristics, at least in response to this α
1-adrenoceptor agonist. In combination with NA (8.2 mM) the constriction was significantly attenuated in half of the preparations. In addition, seven arteries exhibited spontaneous contractile activity which was significantly attenuated by NA in six of them.
Conclusions: NA can significantly attenuate both ‘spontaneous’ and agonist-induced constrictions in tumour-recruited human arteries, though not all arteries are sensitive.
An experimental and analytical investigation is conducted regarding the behavior of Ontario-type reinforced concrete bridge decks. A full-scale bridge deck (both cast-in-place and precast), detailed ...in accordance with the Texas State Department of Highways provisions for Ontario-type decks, and having about 60% of the reinforcement required by the current AASHTO code, performs well under current AASHTO design load levels. Under service and overload conditions (about three times the current AASHTO design wheel load), the behavior of the deck slab is essentially linear. Membrane forces do not noticeably affect the performance of the bridge prior to deck cracking. After cracking, significant compressive membrane forces are present in the deck, and could significantly increase its flexural capacity. Detailed finite element models of the specimen are developed for both the cast-in-place and precast panel deck cases. Cracking of the deck is followed using sequential linear analyses with a smeared cracking model. Analytical predictions agree well with experimental results.
Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel ...through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel.
Holmes Tremor (HT) is an irregular, slow-frequency (<4.5 Hz) tremor characterized by a combination of resting, postural, and action tremors mostly of the upper extremities. Symptoms of HT typically ...emerge 4 weeks to 2 years after a brain injury caused by a spectrum of etiologies. HT pathophysiology is thought to result from aberrant collateral axonal sprouting and synaptic dysfunction following neuronal damage. To date, the dopaminergic nigrostriatal system, cerebello-thalamo-cortical pathway, and dentate-rubro-olivary pathway have all been implicated in the clinical manifestations of HT. The diversity of HT etiologies usually requires a personalized treatment plan. Current treatment options include carbidopa-levodopa, levetiracetam, and trihexyphenidyl, and surgical management such as deep brain stimulation in selected medication-refractory patients. In this review we discuss the pathophysiology, etiology, neuroimaging, and the latest clinical guidelines for care and management of HT.
A procedure has been developed for measuring 147Pm in bioassay samples, based on the separation and preconcentration of 147Pm from the urine matrix by adsorption onto a conventional cation-exchange ...column with final separation and purification by HPLC using dynamic ion-exchange chromatography. The concentration of 147Pm is determined by collecting the appropriate HPLC fraction and measuring the 147Pm by liquid scintillation counting. The limit of detection is 0.1 Bq (3 fg) 147Pm based on a 500-mL sample of urine and a counting time of 30 min with a background of 100 cpm. Ten samples can be processed in 1.5-2 days.
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