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We establish the strong law of large numbers for Betti numbers of random \v{C}ech complexes built on $\mathbb R^N$-valued binomial point processes and related Poisson point processes in the thermodynamic regime. Here we consider both the case where the underlying distribution of the point processes is absolutely continuous with respect to the Lebesgue measure on $\mathbb R^N$ and the case where it is supported on a $C^1$ compact manifold of dimension strictly less than $N$. The strong law is proved under very mild assumption which only requires that the common probability density function belongs to $L^p$ spaces, for all $1\leq p < \infty$., Comment: 30 pages, 2 figures; to be appear in Journal of Statistical Physics

It is established that the immunogenicity of polysaccharides is enhanced by coupling them to carrier proteins. Cross reacting material (CRM

Cross-reacting material 197 (CRM

Coronary artery disease (CAD) and aortic valve stenosis (AS) are frequently coexistent in elderly patients. Our study aimed to compare the inpatient outcomes of transcatheter aortic valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) in hospitalized patients with AS and concomitant

669 Background: Palliative care provides support and improves the quality of life of patients who has terminal illness such as cancer. Studies have shown that integrating palliative care into cancer care soon after the diagnosis of metastatic cancer can improve the quality of life and also prolong survival. The objective of the study was to analyze the acceptance of palliative care and to determine the factors affecting the utilization of palliative care in patients with genitourinary (GU) cancers. Methods: The National Inpatient Sample Database for the year 2016 was queried for the data. Patients who were admitted with a principal diagnosis of Malignant Neoplasm of Prostate (MNP), Renal Cell Carcinoma (RCC), Malignant Neoplasm of Ureter (MNU) were identified using ICD-10 codes and those who had Encounter for Palliative Care (PC) was also identified. Results: A total of 58765 hospitalizations were identified with MNP (n=39853), RCC (n=17786), MNU (n= 1126) during the study period. The total PC utilization for the above patients were 6.4% (n= 3785). Among those, 6.7% (n=1186), 6.3% (n=2531), 6.03% (n=68) from the groups RCC, MNP, MNU respectively received PC. The mean age for the PC utilization was 73 years (MNP= 72 yrs, RCA= 63 yrs, UCC= 73 yrs). Females received more PC when compared to males (6.7% vs 6.4%). Among those who had PC 27.4% (n=1029) died in the hospital. Interestingly, patients who had Medicare and Medicaid had more PC encounters when compared to those with private insurance (OR= 1.21, P= 0.001). Patients admitted on the weekend received more PC when compared to those who admitted during weekdays (OR= 1.12, P= 0.001). Patients admitted to hospitals in the West received more PC than other regions (OR= 1.42, P=0.03). Impact of race, teaching vs non-teaching hospital admissions were not found to be statistically significant in the utilization of PC in the above GU cancers. Conclusions: Medicare and Medicaid patients, weekend admissions, admissions to hospitals in the West received more palliative care. Further studies are needed to reveal the role of socioeconomic status and insurance in the utilization of palliative care in GU malignancies.

69 Background: Prostate cancer is one of the most common cancers in men and one of the leading causes of death among men of all races worldwide. Prostate cancer prevalence and mortality vary substantially by race, ethnicity and geography. The reason behind the disparity is unclear, however, access to screening and treatment, variation in exposure to risk factors, genetic susceptibility, lifestyle practices are the suggested factors that affect the disparity. Methods: We conducted a retrospective analysis of the National Inpatient Sample Database for the year 2016. Patients who were admitted with a principal diagnosis of Malignant Neoplasm of Prostate (MNP) were identified using ICD-10 codes. The epidemiology, racial disparities and regional variations in the mortality of prostate cancer, trend in the cost and length of stay were studied. Results: A total of 39,853 hospitalizations were identified with a principal diagnosis of MNP. The prevalence of MNP was found to be 0.56% with mean age of diagnosis 71.36 ± 0.55. The prevalence of prostate cancer was found to be highest in African Americans (0.65%), followed by Caucasians (0.60%). The disease-specific mortality rate for MNP was 3.45% (n=1,375). African Americans (AA) had 32% more risk of dying with prostate cancer when compared to all the other groups (OR= 1.322, P= 0.001, 95% CI= 1.14-1.52). Caucasians had 25% less chance of dying and Hispanic had 28% less chance of dying with prostate cancer when compared to AA (OR= 0.755, P= 0.001, CI= 0.65-0.87 vs OR= 0.72, P= 0.016, CI= 0.56- 0.94). Those who admitted to West were 22% more likely to die and those admitted to Northeast were 18% more likely to die when compared to Midwest and south regions (OR= 1.22, P= 0.037, CI= 1.01- 1.47 vs OR= 1.18, P= 0.062, CI= 0.91-1.4). The length of stay and also cost of stay were found to be highest for African American population. Conclusions: The prevalence, mortality of prostate cancer, cost and length of inpatient stay were highest among African Americans. There was a statistically significant difference in the mortality rate of prostate cancer based on the hospital regions in the United States. More studies are needed to better understand the reasons behind the regional difference.

This editorial refers to ‘Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial’, by Smithline et al ., BMC Complementary and Alternative Medicine 2019;19:96.

Introduction Disseminated Intravascular Coagulation (DIC) is a systemic coagulopathy which leads to widespread thrombosis and hemorrhage and ultimately results in multiorgan dysfunction. DIC usually occurs as a complication of illnesses like severe sepsis, malignancies, trauma, acute pancreatitis, burns, and obstetrical complications. The prognosis and mortality of DIC depend on the etiology, however, the mortality of DIC is known to be on the higher side. The aim of the study is to analyze if gender, race, regional differences have any association with the mortality of hospitalized patients with DIC. Method The National Inpatient Sample database from the Healthcare Cost and Utilization Project (HCUP) for the year 2016 was queried for data. We identified hospital admissions for DIC with the International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code D65. The data was analyzed with STATA 16.0 version and univariate and multivariate analysis were performed. We studied the characteristics of all such hospitalizations for the year 2016 and the factors associated with the in-hospital mortality rate (MR) of DIC. We used length of stay, cost of stay as an outcome to determine if gender, race, and location play a role in the mortality. Results A total of 8704 admissions were identified with a diagnosis of DIC during the year 2016. The mean age for admission was found to be 56.48± 0.22. The percentage of admissions in females and males did not have a notable difference (50.57% vs 49.43%). The disease specific MR for DIC was 47.7%. Admission during weekend vs weekdays did not carry a statistically significant difference in terms of MR. Females with DIC were less likely to die in the hospital when compared to males with DIC (OR= 0.906, CI 0.82 - 0.99, p= 0.031). Interestingly, African Americans (AA) with DIC admissions were found to have 24% more risk of dying when compared to Caucasians admitted with DIC (OR= 1.24, CI 1.10 - 1.39, P= 0.00), Native Americans (NA) has 67% more risk of dying when compared to Caucasians (OR= 1.67, CI 1.03 - 2.69, p= 0.035). The mortality rate of NA, AA, Caucasians with DIC was found to be 57%, 52%, 47% respectively. The MR was found to be highest in hospitals of the northeast region (52%), then hospitals in the south (47%), followed by west and mid-west (46%), p= 0.000. Patients admitted to west and mid-west were 24% less likely to die when compared to patients admitted to northeast region hospitals (OR= 0.76, p= 0.001). The average length of stay and cost of stay were also less in west and mid-west regions when compared to north east. The difference in outcomes persisted after adjusting for age, gender, race, hospital division, co-morbid conditions. Conclusion Our study demonstrated that African Americans and Native Americans with DIC have high risk of dying in the hospital. Also, there exists a difference between the mortality rate, length and cost of stay among different regions in the United States. More research is needed to elucidate the factors that might be impacting the location-based variation in mortality. Disclosures No relevant conflicts of interest to declare.

Introduction The overall impact of morbidity related to sickle cell disease (SCD) is enormous due to decreased quality of life, high health care utilization and immense financial strain on the patients and health care system. Patients with SCD have also been found have high hospital readmission rates compared to other medical conditions, further leading to increased health care burden. The objective of this study was to explore the common reasons, healthcare utilization and identify modifiable factors associated with 30-day readmission in patients with SCD using the most recently available national data in the United States. Methods Cohort selection. 2016 Nationwide Readmission Database (NRD) from the Healthcare Cost and Utilization Project (HCUP) by the Agency for Healthcare Research and Quality (AHRQ) was queried for analysis. NRD captures discharge data from 22 states, representing about 50% of all hospitalizations in the United States. National estimates can be produced by using sampling weights provided by the NRD. Patients with SCD were identified by using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code D57. Patients younger than 18 years were excluded. Readmission was defined as any admission within 30 days of index hospitalization discharge. Statistical Analysis. Sampling weights were used throughout all calculations, facilitating appropriate national projections. Percentages in all figures reflect national estimates. Chi-square test and Student's t-test were used for univariate analysis. Multivariable logistic regression analysis was done to determine independent predictors of 30-day readmission in patients with SCD. Data analyses was performed using SAS v9.4 (SAS Institute, Cary, NC). Results In a total of 83,692 hospitalizations for SCD in 2016, 15,880 (18.9%) had at least one 30-day readmission and 40% of the readmissions occurred within the first two weeks of discharge. The most common reason for 30-day readmission was due to complications of SCD (29.8%) with sickle-cell pain crisis (18.4%) being the most frequent one. The other common causes for readmission were sepsis (10.3%), cardiac related (9.7%), respiratory failure (6.2%), renal failure (4.3%) and mood related (4.04%). Female sex (P Conclusion This study showed that the 30-day readmission rate in patients with SCD in 2016 has decreased to less than 20% compared to previously published rates (31.9%, Elixhauser A, 2013). While this decrease in readmission rate is encouraging, further studies are needed to investigate the reasons for this trend. Several modifiable risk factors were identified in this study such as alcohol, tobacco, opioid, substance abuse and depression which can be addressed to potentially bring down the readmission rate further and improve patient care. Disclosures No relevant conflicts of interest to declare.

Introduction Sickle cell disease (SCD) associated pain is a significant health care issue in the United States which prompts physicians to prescribe opioids to help treat and prevent the recurrent acute painful episodes. Despite nationwide efforts to reduce narcotic pain medication usage, opioids still remain as the mainstay of pain management in SCD. Many SCD patients are using marijuana to help with their pain, anxiety, appetite, mood and sleep as per recent studies. Cannabinoids in marijuana interact with the body's endocannabinoid system which has receptors in almost every major bodily system. The effect of cannabinoids on these receptors reduces the signaling of inflammatory responses and also reduce cytokine production. Very few states have approved SCD as a qualifying condition for medical marijuana. But we are still unsure about the medical benefits of marijuana in SCD patients as there are very limited studies done so far. In our study, we sought to examine the characteristics and complications of marijuana usage in sickle cell patients. Methods The National Inpatient Sample database for the year 2016 was used to identify admissions with a primary diagnosis of SCD and we grouped patients into those who have a diagnosis of cannabis related disorders (CRD) and those who do not have the diagnosis. ICD- 10 codes are used for identifying the SCD patients and also for CRD. Statistical analysis was performed using STATA and univariate and multivariate analysis were performed. The outcomes that are studied included mortality, length and cost of stay, hospital regions and the association of marijuana use with anxiety, mood disorders. We also studied the association of marijuana with the complications of SCD such as sickle cell pain crisis, vaso occlusive crisis, acute chest syndrome, splenic sequestration, avascular necrosis. Results A total of 37,307 admissions with a principal diagnosis of SCD were identified, out of which 4.09% (N= 1526) had cannabis use disorders. The median age of patients with CRD was found to be 31.21 ± 0.3 when compared to 30.67 ± 0.09 in patients without CRD. Even though SCD admissions were more commonly seen in females when compared to males (61.78% vs 38.22%), cannabis use was seen more associated with males (57.97% vs 42.03%). The in-hospital mortality of SCD was less (0.56%) as compared to the mortality rates of other hematological malignancies. The association of cannabis use with in-hospital mortality was found to be not statistically significant. Also, the median length of stay was less in patients with CRD when compared to patients without CRD (4.88 ± 0.2 vs 5.11 ± 0.03) and also likewise cost of stay. Based on the hospital regions in the US, Cannabis use in SCD was seen more prevalent in South region (44%), then Midwest or north-central (26%), northeast (19%), west (10%) and the result was statistically significant (p= 0.003). The association of cannabis use was not found to be statistically significant with acute chest syndrome and splenic sequestration. Cannabis use was, however, found to be associated with the vaso occlusive crisis and avascular necrosis (OR=1.02, p=0.003 and OR= 1.14, 0.022 respectively) even though we cannot say that cannabis use could be a risk factor as there are other confounding factors like coagulopathy, chronic debilitating conditions. Interestingly, SCD patients with CRD have more risk of developing anxiety (OR= 2.32, p=0.000) and also mood disorders (OR= 2.5, p= 0.001) when compared to SCD patients without CRD. The difference persisted after adjusting for age, gender, race, co-morbidities. Conclusion Marijuana use is more seen in the southern and north-central regions in patients with SCD. Marijuana use was not found to be associated with in-hospital mortality in sickle cell patients. SCD patients are using marijuana mainly for alleviating their pain and sometimes for its euphoria effect. Our study showed that it can cause anxiety and mood disorders. The main limitation of our study was the moderate sample size for SCD patients with CRD. The impact and interaction between CRD and SCD complications need to be evaluated separately in a larger study to get accurate values. Large randomized control trials have to be done to assess if SCD qualifies for prescription of medical marijuana as it possesses benefits as well as risks. Disclosures No relevant conflicts of interest to declare.

Purpose To assess if fully automated localization of the aorta can be achieved using phase contrast (PC) MR images. Materials and Methods PC cardiac-gated MR images were obtained as part of a large population-based study. A fully automated process using the Hough transform was developed to localize the ascending aorta (AAo) and descending aorta (DAo). The study was designed to validate this technique by determining: (i) its performance in localizing the AAo and DAo; (ii) its accuracy in generating AAo flow volume and DAo flow volume; and (iii) its robustness on studies with pathological abnormalities or imaging artifacts. Results The algorithm was applied successfully on 1884 participants. In the randomly selected 50-study validation set, linear regression shows an excellent correlation between the automated (A) and manual (M) methods for AAo flow (r = 0.99) and DAo flow (r = 0.99). Bland-Altman difference analysis demonstrates strong agreement with minimal bias for: AAo flow (mean difference [A-M] = 0.47 ± 2.53 mL), and DAo flow (mean difference [A-M] = 1.74 ± 2.47 mL). Conclusion A robust fully automated tool to localize the aorta and provide flow volume measurements on phase contrast MRI was validated on a large population-based study. J. Magn. Reson. Imaging 2014;40:221–228. © 2013 Wiley Periodicals, Inc.

Femoral shaft fractures are typically the result of a high-energy mechanism such as a motor vehicle accident but can also be associated with falls in the elderly. Femur fractures are often associated with other fractures or head trauma; thus, a thorough physical exam should be performed to assess for these injuries. ATLS protocol should be initiated upon initial evaluation with particular attention paid to circulatory status as large volumes of blood can collect in the thigh after these fractures. Fractures are classified based on location and the degree of comminution using the Winquist and Hansen classification. Operative treatment often consists of intramedullary nail insertion and is typically performed unless comorbidities contraindicate it.

Background: The incidence of Tuberculosis (TB) of elbow is 2-5% of all skeletal locations. Most reports of TB elbow have focused attention on the diagnosis. The management options and classification has been missing. We present a retrospective clinicoradiological analysis of 38 cases (40 elbows) of TB of elbow joint. Materials and Methods: The patients presented with pain, swelling and loss of motion. Two cases had bilateral involvement. The average delay between onset of symptoms and presentation was 8 months. The elbows were classified according to modified Martini's radiological classification, which distinguishes between osseous lesions close to joint line (e.g. coronoid, condyles) and lesions away from the joint line (e.g. epicondyles, olecranon). We modified the classification to subdivide into para-articular bony lesions that had invaded the joint and those that were threatening to invade joint. All patients received antitubercular chemotherapy and immobilization in above-elbow plaster slab for 4-8 weeks. Twenty patients underwent surgical interventions (synovectomy, intraarticular debridement). Results: The average followup period was 5.3 years (range 1.5-14.2 years). The range of movement at final followup averaged 107° for stage 2, 90° for stage 3A, 47° for stage 3B and 32° for stage 4. Range of supination and pronation was less satisfactory as compared to flexion and extension and all elbows with bony involvement had less than 90° arc of supination and pronation. Conclusion: Surgical intervention could appreciably alter the outcome especially in patients with extra-articular involvement close to the joint. We have classified this subgroup separately.

Quiescent (G0) cells are transient cell-cycle-arrested subpopulations in cancers that include dormant cancer stem cells. While leukemic stem cells/minimal-residual-disease were studied transcriptionally, their translation profile and post-transcriptional mechanisms that control their proteome—and thereby, survival—are unknown. We find G0 leukemic cells are chemoresistant, with altered canonical translation and similar proteome and translatome—rather than transcriptome—to cells isolated post-chemotherapy, implicating post-transcriptional regulation in chemoresistance. Mechanistically, we find DNA-damage-responsive-ATM and stress-activated-p38-MAPK/MK2 alter post-transcriptional mechanisms, regulating mRNA-decay-factor, TTP, to increase AU-rich-element-bearing mRNAs. This permits translation of AU-rich-element-bearing pro-inflammatory-cytokine TNFα, and immune modulators (CD47) that promote survival. Co-inhibiting p38-MAPK/MK2 and TNFα—prior to/alongwith chemotherapy—decreases chemoresistance in vivo and in patient samples. Disrupting TTP regulation reduces TNFα and chemoresistance, revealing TTP as a regulator of inflammation-mediated chemoresistance. These studies uncover a pro-inflammatory subpopulation in cancer that enables chemoresistance via DNA-damage- and stress-regulated post-transcriptional mechanisms, and develop a new combination therapy against chemo-survival. Statement of Significance These studies reveal the significance of post-transcriptional regulation of inflammatory/immune response in chemoresistance, mediated by AU-rich-elements, mRNA-decay-regulator TTP, and non-canonical translation. These results reveal DNA-damage/stress-induced TTP as a key regulator of inflammation-mediated chemoresistance and developed a new combination therapy to reduce resistance in cell lines, patient samples and in vivo.

Case reports have documented arrhythmias from marijuana (cannabis) use. However, the overall prevalence of arrhythmias in marijuana users and their impact on healthcare have not been described previously. The National Inpatient Sample database was queried for the year 2016. Marijuana use and

Fish and commercially available fish oil preparations are rich sources of long-chain omega-3 polyunsaturated fatty acids. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most important fatty acids in fish oil. Following dietary intake, these fatty acids get incorporated into the cell membrane phospholipids throughout the body, especially in the heart and brain. They play an important role in early brain development during infancy, and have also been shown to be of benefit in dementia, depression, and other neuropsychiatric disorders. Early epidemiologic studies show an inverse relationship between fish consumption and the risk of coronary heart disease. This led to the identification of the cardioprotective role of these marine-derived fatty acids. Many experimental studies and some clinical trials have documented the benefits of fish oil supplementation in decreasing the incidence and progression of atherosclerosis, myocardial infarction, heart failure, arrhythmias, and stroke. Possible mechanisms include reduction in triglycerides, alteration in membrane fluidity, modulation of cardiac ion channels, and anti-inflammatory, anti-thrombotic, and anti-arrhythmic effects. Fish oil supplements are generally safe, and the risk of toxicity with methylmercury, an environmental toxin found in fish, is minimal. Current guidelines recommend the consumption of either one to two servings of oily fish per week or daily fish oil supplements (around 1 g of omega-3 polyunsaturated fatty acids per day) in adults. However, recent large-scale studies have failed to demonstrate any benefit of fish oil supplements on cardiovascular outcomes and mortality. Here, we review the different trials that evaluated the role of fish oil in cardiovascular diseases.

This study aims to compare ethnic difference in proximal aortic pulse wave velocity (PWV) and characteristic impedance (Zc).Increased aortic stiffness is an independent predictor of target organ damage, incident hypertension, and all-cause mortality. However, previous studies have not directly assessed proximal aortic function in Blacks, the ethnic population with disproportionately high risk for incident hypertension and target organ complications.We evaluated the multiethnic, population-based DHS (Dallas Heart Study) participants (N = 2,544, 54.2% women, 49.7% Black) who underwent cardiac magnetic resonance at 1.5-T. Aortic stiffness and Zc were determined from aortic arch PWV and lumen area measurements. Linear regression was used to evaluate ethnic differences in proximal aortic wall stiffness using aortic arch PWV and Zc as dependent variables with and without adjustment for traditional cardiovascular risk factors. Because cardiac output was significantly higher in Blacks compared to Whites and Hispanics, additional comparisons of PWV and Zc were performed after adjustment for cardiac output and peripheral vascular resistance.Compared with Whites, both Blacks and Hispanics had higher levels of aortic arch PWV (4.25, 95% confidence interval [CI]: 4.15 to 4.35 m/s, vs. 4.72, 95% CI: 4.64 to 4.81 m/s, vs. 4.48, 95% CI: 4.33 to 4.63 m/s, respectively, both p 0.05 vs. White), and Zc (64.9, 95% CI: 63.3 to 66.6 dyne·s/cmIn a multiethnic population-based-sample, Blacks and Hispanics had higher proximal aortic stiffness compared with Whites independent of blood pressure and relevant risk factors.

A communication satellite payload consists of receiving and transmitting antennas and all the electronic equipment which supports the transmission of the carriers. The overall satellite payload bandwidth is split into several sub-bands. The amplifying chain associated with each sub-band is called a satellite channel, or transponder. A typical satellite communication transponder comprises of wide band receivers followed by an analog channelization assembly, power amplifier and an output combiner. In order to characterize the performance of the transponder given only the measured results such as magnitude and phase response, the transponder subsystems can be modelled in a suitable software or hardware. A satellite emalator consists of many sub-systems but the paper would focus on filters imelemented in a setellite payload. These include Preselect Filter (PSF), Input Multiplexer (IMUX) and Output Multiplexer (OMUX) and Harmonic Reject Filter (HRF). This paper illustrates the emulation of characteristics of diffprent band pass filters implemented in the communication payload using digital filters. A generic fixed pole FIR filter was designed which was further tested for PSF, IMUX, OMUX and HRF filter response.

Background Cardiovascular magnetic resonance (CMR) has been validated for the noninvasive assessment of total arterial compliance and aortic stiffness, but their associations with cardiovascular outcomes is unknown. The purpose of this study was to evaluate associations of CMR measures of total arterial compliance and two CMR measures of aortic stiffness with respect to future cardiovascular events. Methods The study consisted of 2122 Dallas Heart Study participants without cardiovascular disease who underwent CMR at 1.5 Tesla. Aortic stiffness was measured by CMR-derived ascending aortic distensibility and aortic arch pulse wave velocity. Total arterial compliance was calculated by dividing left ventricular stroke volume by pulse pressure. Participants were monitored for cardiovascular death, non-fatal cardiac events, and non-fatal extra-cardiac vascular events over 7.8 ± 1.5 years. Cox proportional hazards regression was used to assess for associations between CMR measures and cardiovascular events. Results Age, systolic blood pressure, and resting heart rate were independently associated with changes in ascending aortic distensibility, arch pulse wave velocity, and total arterial compliance (all p

In this study, it is found that, for Bacillus subtilis, citrate–glucose cometabolism leads to zero acid production over a wide range of growth rates and nearly theoretical carbon yield. Experimental results are presented that point to pyruvate kinase (PYK) as a site of citrate-mediated glycolytic flux attenuation. First, the measured fluxes show that, compared with cultures grown on glucose, the PYK flux drops by more than tenfold when citrate is added. Second, relative to cultures metabolizing glucose, the phosphoenolpyruvate (PEP) pool elevates substantially, whereas the pyruvate pool drops, when citrate is present. Finally, our modeling results indicate that maximizing carbon yield corresponds to nearly eliminating pyruvate kinase (PYK) flux and that the pyruvate supplied by the PEP-consuming glucose transport system can supply the biosynthetic requirements. A literature review suggests some mechanisms for how PYK attenuation by citrate addition can occur. At this juncture, we hypothesize that direct PYK inhibition occurs which, in turn, also leads to phosphofructokinase inhibition via the elevated PEP pool. These two inhibition events combine to throttle glycolytic flux; minimize acid formation; and substantially increase cellular, product, and energetic yields. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 129–134, 1999.

Our prior work revealed that compared to the case for glucose metabolism, increased carbon yield and nil acid formation result when Bacillus subtilis grows on glucose medium containing citrate. To scrutinize further how citrate addition may alter metabolic flux regulation and the degree that the observed carbon yield corresponds to the maximal value, experimental (by least-squares analysis) and optimal (by linear programming) fluxes and yields were contrasted. Networks with differing reaction routes, directionality constraints, and transhydrogenase activities were examined. To attain an elevated carbon yield, citrate-glucose utilization need not alleviate any stoichiometric constraints that can sometimes interfere with the attainment of network objectives. Rather, the high carbon yield and nil acid formation attained may be linked to restriction of glycolytic capacity, particularly at the level of pyruvate kinase, which is consistent with a hypothesized effect of coupled metal-citrate uptake. Allowing for malic enzyme activity, hexose monophosphate pathway cycling, and transhydrogenase activity may also lead to the flux distributions underlying the high carbon yield observed. Finally, the observed carbon yield corresponded well to the maximum yield provided by all the network alternatives examined. Collectively, these results suggest that (i) the observed carbon yield is essentially equal to the maximal values associated with plausible networks and (ii), as suggested by others, nonoptimal flux regulation may contribute significantly to apparent cellular maintenance requirements.

This work describes a novel technique of designing a low noise high gain CMOS instrumentation amplifier for biomedical applications. A three op-amp instrumentation amplifier have been designed by employing two simple op-amps at the two inputs and a folded cascode op-amp at the output. Both input and output stage op-amps are 2-stage. Most of the earlier designed op-amp in literature uses same type of op-amp at the input and output stages of instrumentation amplifier. By using folded cascode two stage op-amp at the output, we have achieved significant improvement in gain and CMRR. Transistors sizing plays a vital role in achieving high gain and CMRR. To achieve a desirable gain, common mode rejection ratio and other performance metrics, selection of most appropriate op-amp circuit topologies & optimum transistor sizing was the main criteria for design of instrumentation amplifier for biomedical applications. The instrumentation amplifier is simulated using Cadence Spectre tool and layout is designed in Cadence Layout editor at 0.18µm CMOS technology. Each of the input op-amp provides a gain and CMRR of 45dB and 72dB respectively. The output stage folded cascode amplifier provides a gain of 82dB and a CMRR of 92dB. The design achieves an overall gain and CMRR of 67dB and 92db respectively. The designed instrumentation amplifier consumes only 263µW of power suitable for biomedical signal processing applications. DOI: http://dx.doi.org/10.11591/ijece.v3i4.3170

Purpose.To evaluate the tibial articular cartilage and histology of the posterior cruciate ligament (PCL) in osteoarthritic knees so as to determine predictors of PCL degeneration.Methods.23 advanced osteoarthritic knees (mean patient age, 61 years) treated with total knee arthroplasty (TKA) were prospectively studied. The Knee Society Score was assessed. Osteoarthritic changes on radiographs were graded as mild, moderate, or severe. Tibial articular cartilage erosion was assessed. The appearance of both cruciate ligaments was classified as normal, abnormal (thinner and sclerotic), or ruptured. Both ligaments were examined histologically for degenerative changes. Each degenerative change of the PCL was graded by 2 histopathologists twice separately. Higher scores indicated more severe degeneration.Results.Of the 23 knees, the gross appearance of the anterior cruciate ligaments (ACLs) was normal in 6, abnormal in 11, and ruptured in 6. Histologically, the PCLs were normal in 4, minimally degenerated in 2, mildly in 8, moderately in 5, and severely in 4. The predominant degenerative change was the presence of loose fibrous tissue. ACL appearance correlated positively with PCL degeneration ( r=0.883, p=0.001). The mean Knee Society Score was 24 (range, 0–43), and the mean function score was 30 (range, 5–55). PCL degeneration correlated positively with the Knee Society Score ( r=0.565, p=0.02) but not with the function score ( r=0.061, p=0.447). Anteroposterior instability correlated positively with PCL degeneration ( r=0.691, p=0.01). Erosion in the lateral tibiofemoral compartment and ACL insufficiency were indicators of PCL degeneration (despite a normal appearance). Inter-observer reliability and intra-observer reproducibility were 0.82 and 0.87, respectively.Conclusion.The Knee Society Score, anteroposterior instability, ACL appearance, and erosion in the lateral tibiofemoral compartment are predictors of PCL degeneration and can help decide on the optimal type of TKA implant (PCL-retaining vs. PCL-sacrificing design).

This study compares the immunogenicity and safety of a single dose of a new meningococcal A conjugate vaccine (PsA-TT, MenAfriVac™, Serum Institute of India Ltd., Pune) against the meningococcal group A component of a licensed quadrivalent meningococcal polysaccharide vaccine (PsACWY, Mencevax ACWY(®), GSK, Belgium) 28 days after vaccination in Indian children. This double-blind, randomized, controlled study included 340 Indian children aged 2-10 years enrolled from August to October 2007; 169 children received a dose of PsA-TT while 171 children received a dose of PsACWY. Intention-to-treat analysis showed that 95.2% of children in PsA-TT group had a ≥4-fold response in serum bactericidal titers (rSBA) 28 days post vaccination as compared to 78.2% in the PsACWY group. A significantly higher rSBA GMT (11,209, 95%CI 9708-12,942) was noted in the PsA-TT group when compared to PsACWY group (2838, 95%CI 2368-3401). Almost all children in both vaccine groups had a ≥4-fold response in group A-specific IgG concentration but the IgG GMC was significantly greater in the PsA-TT group (89.1 μg/ml, 95%CI 75.5-105.0) when compared to the PsACWY group (15.3 μg/ml, 95%CI 12.3-19.2). Local and systemic reactions during the 4 days after immunization were similar for both vaccine groups except for tenderness (30.2% in PsA-TT group vs 12.3% in PsACWY group). None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children.

It is well recognized that metabolic fluxes are the key variables that must be determined in order to understand metabolic regulation and patterns. However, owing to difficulties in measuring the flux values, evaluation of metabolic fluxes has not been an integral part of the most metabolic studies. Flux values for metabolites of glycolysis, tricarboxylic acid (TCA) cycle, and hexose monophosphate (HMP) pathway were obtained for batch and glucose-limited continuous cultures of Bacillus subtilis by combining the information from the stoichiometry of key biosynthetic reactions with the experimental data on concentrations of glucose and metabolic by-products, CO(2) evolution, and oxygen uptake rates. The results indicate that (1) the metabolic fluxes and energetic yield as well as the extent of flux mismatch in metabolic activity of glycolysis and the TCA cycle reactions can be accurately quantified; (2) the flux through the TCA cycle in continuous culture is much in excess of cell energetic and biosynthetic demands for precursors; (3) for the range of growth rates examined the TCA cycle flux increases almost in proportion to growth rate and is significantly repressed only at very high growth rates of batch cultures; and (4) for continuous cultures the isocitrate dehydrogenase catalyzed reaction of the TCA cycle is the major source of the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) used in biosynthesis.

Thermostable vaccines promise to simplify the logistics of vaccine distribution and expand the immunization coverage. In this study, a pilot-scale spray drying process was developed and used to produce glassy state formulations of a recombinant hepatitis B (HepB) vaccine containing aluminum adjuvant and Neisseria meningitidis A (MenA) protein-polysaccharide conjugate vaccine, representing two common types of subunit vaccines in use today: the spray-dried HepB vaccine formulations were stable for at least 24 months at 37 degrees C while several MenA vaccine formulations exhibited complete stability at temperatures up to 60 degrees C. This study demonstrates the feasibility of producing thermostable vaccines with advanced processing and formulation technologies.

Crush injuries of the foot are one of the most difficult and challenging tasks for a trauma surgeon to manage in terms of limb salvage and provision of a painless functional foot. Injuries to the foot, especially the hindfoot, account for almost 24.6% of all the warfare injuries in Afghanistan, of which more than 70% end in amputation for various reasons. We devised a method using the principles of Ilizarov’s distraction osteosynthesis to salvage limbs with bony defects in the hindfoot which otherwise were candidates for amputation. The procedure is done in two stages. Initially, the ring fixator is applied for the soft tissue reconstruction and infection control, and the next stage consists of percutaneous “inverted L”-shaped osteotomy in the posterior half of the lower tibia. The study included 32 patients with hindfoot crush injuries involving talus, calcaneum, a combination of both, or even involving the adjacent tarsal bones. All these crush injuries were classified using the Gustilo and Anderson classification. The postoperative functional assessment of the feet was done using the Maryland Foot Score system with a minimum follow-up of four years. We had good results in 53%, fair in 34% and failure in 13% of our cases. The complications of this procedure were the same as with the use of the ring fixator elsewhere in the body. This method provides a technique to salvage the foot and produce a painless, stable, fused foot in one of the most difficult settings of a hindfoot crush injury.

The ability of plants to metabolize the xenobiotic nitrate ester, glycerol trinitrate (GTN, nitroglycerin), was examined using cultured plant cells and plant cell extracts. Intact cells rapidly degrade GTN with the initial formation of glycerol dinitrate (GDN) and the later formation of glycerol mononitrate (GMN). A material balance analysis of these intermediates indicates little, if any, formation of reduced, conjugated or cell-bound carbonaceous metabolites. Cell extracts were shown to be capable of degrading GTN with the simultaneous formation of GDN in stoichiometric amounts. The intermediates observed, and the timing of their appearance, are consistent with a sequential denitration pathway that has been reported for the microbial degradation of nitrate esters. The degradative activities of plant cells are only tenfold less than those reported for bacterial GTN degradation. These results suggests that plants may serve a direct degradative function for the phytoremediation of sites contaminated by organic nitrate esters.

The feasibility of continuous production of proteins in chemostat cultures of Bacillus subtilis was investigated. An expression system consisting of the bacterium B. subtilis BR151 carrying plasmid p602/19 was used. The plasmid contains the cat (chioramphenicol acetyltrans-ferase) gene downstream of a strong vegetative T5 promoter. It was found that, at a dilution rate of 0.2 h(-1) production of relatively high levels of CAT protein (about 4% ofcellular protein) can be sustained. But, experiments at a higher dilution rate of 0.4 h(-1) were unproductive because of high acidformation and washout. Combination of low cell yield, which results from excessive acid formation, and low dilution rate led to a low volumetric CAT productivity. Our recent work with the nonrecombinant cells, has demonstrated that uptake of small amounts of citrate significantly reduces or entirelyeliminates the acid formation. This superior performance in the presence ofcitrate was hypothesized, based on strong experimental evidence, to be the result of a reduction in glycolysis flux through a sequence of events leading to a reduction in pyruvate kinase and phosphof- ructokinase activities, the regulatory enzymes of glycol-ysis. In this study, it is demonstrated that cofeeding of glucose and citrate substantially reduces theorganic acid formation and significantly increases the recombinant culture productivity. The combination of high specific CAT activity and cell density resulted in a total of six- to tenfold higher culture productivitywhen citrate and glucose were cometabolized than when glucose was the only carbon source. (c) 1995 John Wiley & Sons Inc.

The results from the experiments performed with a mutant deficient in citrate synthase activity can be summarized as follows. (1) Totally blocking entry into the TCA cycle did not appreciably alter the cellular ATP yield. The unchanged yield suggests that for growth on abundant glucose, the sensitivity of ATP yield to TCA cycle flux is low. ATP production in the mutant is altered, in part, by modulating the relative amounts of formate and acetate produced. (2) The in vivo operation of pyruvate-formate lyase and malic enzyme corresponds to proposals developed from in vitro studies. Namely, pyruvate activates the former, and acetyl CoA inhibits the latter. Overall, the diversion of pyruvate to formate under aerobic conditions constitutes an adaptation of the mutant to the enzymatic lesion. The low alpha-ketoglutarate dehydrogenase flux estimated for the mutant indicates that the enzyme is highly repressed in cells growing rapidly on glucose, which is in accord with prior induction-repression studies. Moreover, the lack of a change in uptake flux during the bulk of batch growth is consistent with prior induction-repression studies. (3) The mutant exhibits a heightened sensitivity to CO2 as compared to wild-type counterparts. Growth rate is increased, and the production of formate, malate, glycerate, and pyruvate is reduced. This sensitivity illustrates that citrate synthase is more than an expendable component in an amphibolic pathway. Its presence in wild-type cells "immunizes" against the effect of CO2 fluctuations. (4) The effects of CO2 can be tentatively explained by assuming that the PEP carboxylase-catalyzed reaction is stimulated.