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Knowledge of proper clinical management of drug overdose and chemical and biological toxin exposure is important for the neurocritical care specialist. Many of the common offenders principally affect the central nervous system (CNS). Even those that do not will lead to a severely incapacitated state when overdosed such that the afflicted patient will require critical care in an intensive care unit (ICU).
Discrete unstable modes of hypersonic laminar boundary layers, obtained from an eigenvalue analysis, provide insight into key transition scenarios. The character of such modes near the leading edge is often identified with the corresponding asymptotic free-stream behaviour of acoustic, vortical or entropic (thermal) content, which we designate fluid-thermodynamic (FT) components. In downstream regions, however, this direct one-to-one correspondence between discrete modes and FT components does not hold, since FT components interact in well-defined ways with the basic state and with each other (even under linear scenarios). In the present work, we perform an FT decomposition of discrete modes using momentum potential theory, to yield a physics-based analysis that complements linear stability theory in the linear regime, and seamlessly extends to the nonlinear domain where direct numerical simulations are appropriate. Linear and nonlinear saturated disturbance effects, different forcing types and wall thermal conditions are considered, with emphasis on phenomena occurring near stability-mode synchronization locations. The results show that, in the linear regime, each discrete mode contains all FT components, whose relative amplitudes vary with streamwise distance. Vortical components are always the largest, followed by thermal and acoustic components. These latter two show distinct fore and aft signatures near mode synchronization. The vortical component displays a series of rope-shaped recirculation-cell patterns across the generalized inflection point. However, both acoustic and thermal components display ‘trapped’ structures. The former contains an alternating monopole array between the wall and the critical layer, while the latter is confined to an undulating region between the wall and a wavy locus straddling the generalized inflection point. Nonlinear saturation in the region of Mack-mode growth further strengthens the rope-shaped structures in the vortical component and higher harmonics appear, whose form and location depend on the specific component. Wall cooling modifies the eigenfunctions such that the acoustic component accounts for more of its composition, consistent with its destabilization. Analysis of energy interactions among the FT components indicates that, even though the vorticity component is the largest, the thermal component induces the most significant source term for the growth of acoustic perturbations, possibly due to the trapped nature of both.
Background: The KCNT1 gene encodes subunits of the Na+-activated K+ channel, widely expressed in the CNS. Mutations of this gene have been implicated in Malignant Migrating Partial Seizures of Infancy (MMPSI). This early-onset epileptic encephalopathy represents a challenge due to pharmacoresistance. The channel-specific mutation represents the potential for targeted pharmacotherapy. Quinidine is a partial antagonist of the KCNT1 encoded channel; patients with MMPSI have been reported to have responded to doses ranging 34.4/kg/d - 60mg/kg/d. We present a case of MMPSI with a KCNTI mutation (c.G1283A:p.R428Q) trialled on quinidine. Methods: Following ineffective trials of 6 anti-seizure medications, this patient was trialled on oral quinidine. This patient was titrated up to a dose of 52mg/kg/d. Twenty-four hour EEG monitoring prior to quinidine therapy, and at target dose were compared. Results: Prior to initiation of quinidine, this patient experienced 22 electrographic seizures over 24 hours. At target dose, this patient experienced greater than 70 seizures over 24 hours. Conclusions: Quinidine has previously been reported to be effective in patients with MMPSI with the same and different mutations. We report the second case of a patient with MMPSI and KCNT1 mutation R428Q with poor clinical response to quinidine.
Background: Hemimegalencephaly (HME) is a hamartomatous malformation of one cerebral hemisphere, resulting in refractory epilepsy, intellectual disability, and autistic features. Hemispherectomy is the definitive treatment, but there is risk of high morbidity and mortality, especially when done in early infancy. Various preclinical studies have shown that dysregulation of the mTOR pathway has an integral role in the development of various epilepsy syndromes, including tuberous sclerosis complex (TSC), focal cortical dysplasia and HME. Recently, mTOR inhibitors were proven to be effective in treating seizures in TSC. Methods: We present a case of a 6 day old female with refractory epilepsy despite the trial of 9 anti-seizure medications and the ketogenic diet. As the patient was awaiting epilepsy surgery, an mTOR inhibitor, rapamycin was initiated. Results: After 1 week of the initiation, she had over a 50% reduction in seizures. At two weeks, the parents felt that for the first time, she was making developmental gains. She also appeared brighter and more interactive. Due to her response to treatment, her hemispherectomy was deferred to when she is older, so there will be a decreased risk of complications from the surgery. Conclusions: This case exemplifies how mTOR inhibitors should be considered as a treatment option for patients with HME and refractory epilepsy.
Background: Perampanel (PER) is a new anti-seizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is available in Canada for children since 2014. It is important for physicians to be aware of the efficacy and tolerability of drugs in the post-marketing phase. Methods: We did a retrospective review of our experience with PER at BC Children’s Hospital. Patients on PER were identified. Clinical data, including demographics, efficacy, tolerability, adverse effects (AE) and retention rates were obtained by review of clinical records. Results: Of 24 patients pediatric patients prescribed PER, 21 (87%) had focal and three had symptomatic generalized epilepsy. Ten (42%) had greater than 50% reduction in seizures. In fifteen patients, (63%) PER was discontinued due to AE or poor response. Twelve (50%) had behavioral AE and eight (33%) had non-behavioral AE. PER was effective, at lower doses than required for adults. One third experienced serious AE. One patient experienced oculogyric crisis, not previously reported with PER. AE were not associated with high doses and were reversible. Possible risk factors for behavioral AE include behavioral problems with other medications and pre-existing behavioral co-morbidities. Conclusions: It is important for clinicians to be aware of and counsel patients about serious AE, particularly behavioral, when prescribing PER.
Large-eddy simulation data for a Mach 1.3 round jet are decomposed into acoustic, hydrodynamic and thermal components using Doak’s momentum potential theory. The decomposed fields are then analysed to examine the properties of each mode and their dynamics based on the transport equation for the total fluctuating enthalpy. The solenoidal fluctuations highlight hydrodynamic components of the jet and capture the shear layer growth and breakdown process. The acoustic mode exhibits a jittering coherent wavepacket structure in the turbulent region and consequent highly directional downstream radiation. The expected radial decay rates,
for hydrodynamic and
for acoustic, are recovered and closely follow the universal radiation spectra in the sideline and downstream directions. The scalogram of the acoustic mode in the near-acoustic-field region is consistent with that of the pressure perturbation signal in the acoustic-frequency range, but effectively removes the hydrodynamic and thermal content. The time-resolved and mean behaviour of terms in the total fluctuating enthalpy equation is analysed in detail. A large-scale intermittent event in the near-acoustic field is shown to be associated with an intrusion of vortices from the shear layer into the core of the jet. Acoustic sources are created when the resulting negative fluctuations in the solenoidal component interact with positive fluctuations in the Coriolis acceleration term. The latter are associated with regions of high vorticity on the inner side of the shear layer. In contrast, sinks result from the interaction of solenoidal momentum fluctuations with positive entropy gradients along entrainment streaks.
Background: Epileptic encephalopathy (EE) is a severe condition in which epileptic activity itself may contribute to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone. Next generation sequencing technologies such as whole exome sequencing (WES) can detect underlying genetic causes of in EE. Methods: This report describes genotype-phenotype correlation of 29 subjects with unexplained epileptic encephalopathy, in whom WES, targeting a list of 557 epilepsy-associated genes was performed. Epilepsy phenotyping was done according to current ILAE recommendations. Results: Median age at seizure onset was 14 months (range 1-48). Electroclinical syndromes were applicable for 16/29, 8/16 had a definite/likely diagnosis. 6/8 subjects with West syndrome had variants in ALG13, STXBP1, PAFAH1B1, SLC35A2, CDKL5 and ADSL. 2 patients with Dravet syndrome had variants in SCN1A and PCDH19 respectively. 4/29 had unspecified EE and definite/likely diagnosis due to STXBP1, POLG, and KCNQ2 (2) variants. 4/29 had a possible diagnosis involving GABRB3, ARHGEF9, PCDH19 and SCN3A variants. Conclusions: The high diagnostic yield (definite/likely diagnosis in 11/29 = 38%), involving a broad variety of epilepsy-associated genes in different electroclinical syndromes justifies the diagnostic approach of early onset EE by next generation sequencing.
To assess the time-dependent exposure of California healthcare facilities to patients harboring methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae, and Clostridium difficile infection (CDI) upon discharge from 1 hospital.
Retrospective multiple-cohort study of adults discharged from 1 hospital in 2005–2009, counting hospitals, nursing homes, cities, and counties in which carriers were readmitted, and comparing the number and length of stay of readmissions and the number of distinct readmission facilities among carriers versus noncarriers.
We evaluated 45,772 inpatients including those with MRSA (N=1,198), VRE (N=547), ESBL (N=121), and CDI (N=300). Within 1 year of discharge, MRSA, VRE, and ESBL carriers exposed 137, 117, and 45 hospitals and 103, 83, and 37 nursing homes, generating 58,804, 33,486, and 15,508 total exposure-days, respectively. Within 90 days of discharge, CDI patients exposed 36 hospitals and 35 nursing homes, generating 7,318 total exposure-days. Compared with noncarriers, carriers had more readmissions to hospitals (MRSA:1.8 vs 0.9/patient; VRE: 2.6 vs 0.9; ESBL: 2.3 vs 0.9; CDI: 0.8 vs 0.4; all P<.001) and nursing homes (MRSA: 0.4 vs 0.1/patient; VRE: 0.7 vs 0.1; ESBL: 0.7 vs 0.1; CDI: 0.3 vs 0.1; all P<.001) and longer hospital readmissions (MRSA: 8.9 vs 7.3 days; VRE: 8.9 vs 7.4; ESBL: 9.6 vs 7.5; CDI: 12.3 vs 8.2; all P<.01).
Patients harboring antibiotic-resistant pathogens rapidly expose numerous facilities during readmissions; regional containment strategies are needed.
Infect. Control Hosp. Epidemiol. 2015;36(11):1275–1282
Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.
Background: For adolescents with epilepsy, there is often a poor system in place to meet their individualized transition needs. Our objectives were 1) to develop epilepsy-specific transition care management plans (TCMPs) to ensure access, and attachment to adult healthcare providers, and 2) to identify strategies for providing support during the transition period, including through the development of physician and patient (or caregiver) navigated web-based tools, resources and recommendations for health system improvements. Methods: Physicians and nurses with expertise in areas including adult and pediatric epilepsy, family medicine, psychiatry, and varied allied health professionals were engaged to generate epilepsy-related TCMPs. Results: Through an iterative process spanning the course of over a year, TCMPs were developed to cover areas including: treatment responsive and resistant epilepsy, ketogenic diet, epilepsy surgery, women’s issues, mental health, and psychosocial aspects of epilepsy. The TCMPs referenced established guidelines and best practices in the literature wherever possible. Caregiver roles and responsibilities were outlined, remaining cognoscent of available provincial resources. Conclusions: Epilepsy specific TCMPs can be developed through a collaborative approach between pediatric and adult healthcare providers, easing the patient experience, creating educated accountability, and providing a forum to identify and address gaps of care in adolescents with epilepsy.
The study characterizes a collection of 67 neonatal septicaemic Escherichia coli isolates on the basis of phylogroup, serotype, virulence, antibiotic resistance and also the association of CTX-M-producing E. coli and the ST131 clone in a developing country. Phylogroups B2 and D were predominant (33% and 19%, respectively). The most prevalent virulence factors (VFs) were traT (69%) and iucC (68%) and most VFs were concentrated in the B2 isolates. High levels of resistance (⩾70%) to cefotaxime, ciprofloxacin and trimethoprim/sulfamethoxazole was recorded but meropenem remained the most active antimicrobial. Six (9%) of the study isolates belonged to the ST131 clone, five of which were from the same hospital, and were either indistinguishable or closely related by pulsed-field gel electrophoresis. Although the prevalence of CTX-M-15-producing isolates was high (81%), the ST131 clone was relatively infrequent (11%) in extended spectrum β-lactamase (ESBL)-producers. The ST131 clone was characterized by the presence of blaCTX-M-15, qnrS, aac(6′)-Ib-cr, IncF plasmids and virulence determinants such as iucC, papC, traT, usp, hlyA, iroNE.coli, cnf, and sat. We conclude that clonal spread of ST131 did not contribute directly to the high prevalence of CTX-M-15 in our settings.
Across 366 California hospitals, we identified hospital-level characteristics predicting increased hospital-associated Clostridium difficile infection (HA-CDI) rates including more licensed beds, teaching and long-term acute care (LTAC) hospitals, and polymerase chain reaction testing. Adjustment for these characteristics impacted rankings in 24% of teaching hospitals, 13% of community hospitals, and 11% of LTAC hospitals.
Insulin-like growth factor binding protein-5 (IGFBP-5) is a key molecule in
mammary gland development, which facilitates the removal of mammary epithelial
cells (MECs) by apoptosis that takes place during remodeling of the mammary
gland during involution. IGFBP-5 binds with IGFs for their bioavailability.
IGFBP-5 has been reported to perform pleiotropic roles such as cellular
apoptosis, proliferation and differentiation. To understand the role of IGFBP-5
during lactation and clinical mastitis, expression profiling of IGFBP-5 at the
protein level was performed in both indigenous cows (Bos
indicus) and buffaloes (Bubalus bubalis) belonging to
two different breeds – Sahiwal cows and Murrah buffaloes.
Reverse-transcriptase PCR (RT-PCR) of IGFBP-5 mRNA confirmed its expression in
milk somatic cells and MECs of Sahiwal cows. ELISA was performed for
quantitative measurement of IGFBP-5 concentrations in milk during different days
(0, 50, 100, 150, 200, 250 and 300) of lactation, during the involution period
and in animals exhibiting short lactation and clinical mastitis. The highest
concentration of IGFBP-5 in milk was observed during the involution period
followed by colostrum, late and early lactation, respectively, in both cattle
and buffaloes. No significant difference in the concentration of IGFBP-5 was
observed during the first 150 days of lactation between cows and buffaloes.
However, higher concentration of IGFBP-5 was observed in cows during late
lactation (200 to 300 days) in comparison with buffaloes. To validate the ELISA
data, quantitative real-time PCR was performed in MECs of Sahiwal cows. The
relative mRNA abundance of IGFBP-5 was found to be significantly
(P<0.05) higher on day 15 than between 50 and 150
days of lactation in case of Sahiwal cows. Highest mRNA expression of IGFBP-5
was observed around 300 days of lactation followed by 200 and 250 days
(P<0.05), respectively. Murrah buffaloes showed
low levels of IGFBP-5 protein in milk as compared with Sahiwal cows during
lactation in ELISA. Animals having history of short lactation length (short
lactating animals) showed higher levels of IGFBP-5 expression (at protein level)
in comparison with normal lactating animals. We propose that higher level
IGFBP-5 expression may have functional significance in lactation persistency. As
a pro-apoptotic molecule, higher expression of IGFBP-5 was observed to be
inversely related to lactation length and milk production.
States have established public reporting of hospital-associated (HA) infections—including those of methicillin-resistant Staphylococcus aureus (MRSA)—but do not account for hospital case mix or postdischarge events
Identify facility-level characteristics associated with HA-MRSA infection admissions and create adjusted hospital rankings.
A retrospective cohort study of 2009–2010 California acute care hospitals. We defined HA-MRSA admissions as involving MRSA pneumonia or septicemia events arising during hospitalization or within 30 days after discharge. We used mandatory hospitalization and US Census data sets to generate hospital population characteristics by summarizing across admissions. Facility-level factors associated with hospitals’ proportions of HA-MRSA infection admissions were identified using generalized linear models. Using state methodology, hospitals were categorized into 3 tiers of HA-MRSA infection prevention performance, using raw and adjusted values.
Among 323 hospitals, a median of 16 HA-MRSA infections (range, 0–102) per 10,000 admissions was found. Hospitals serving a greater proportion of patients who had serious comorbidities, were from low-education zip codes, and were discharged to locations other than home were associated with higher HA-MRSA infection risk. Total concordance between all raw and adjusted hospital rankings was 0.45 (95% confidence interval, 0.40–0.51). Among 53 community hospitals in the poor-performance category, more than 20% moved into the average-performance category after adjustment. Similarly, among 71 hospitals in the superior-performance category, half moved into the average-performance category after adjustment.
When adjusting for nonmodifiable facility characteristics and case mix, hospital rankings based on HA-MRSA infections substantially changed. Quality indicators for hospitals require adequate adjustment for patient population characteristics for valid interhospital performance comparisons.
Infect Control Hosp Epidemiol 2014;35(10):1263–1270
To evaluate whether an ecologic inverse association exists between methicillin-susceptible Staphylococcus aureus (MSSA) prevalence and methicillin-resistant S. aureus (MRSA) prevalence in nursing homes.
We conducted a secondary analysis of a prospective cross-sectional study of S. aureus prevalence in 26 nursing homes across Orange County, California, from 2008–2011. Admission prevalence was assessed using bilateral nares swabs collected from all new residents within 3 days of admission until 100 swabs were obtained. Point prevalence was assessed from a representative sample of 100 residents. Swab samples were plated on 5% sheep blood agar and Spectra MRSA chromogenic agar. If MRSA was detected, no further tests were performed. If MRSA was not detected, blood agar was evaluated for MSSA growth. We evaluated the association between MRSA and MSSA admission and point prevalence using correlation and linear regression testing.
We collected 3,806 total swabs. MRSA and MSSA admission prevalence were not correlated (r = −0.40, P = .09). However, MRSA and MSSA point prevalence were negatively correlated regardless of whether MSSA prevalence was measured among all residents sampled (r = −0.67, P = .0002) or among those who did not harbor MRSA (r = −0.41, P = .04). This effect persisted in regression models adjusted for the percentage of residents with diabetes (β = −0.73, P = .04), skin lesions (β = −1.17, P = .002), or invasive devices (β = −1.4, P = .0006).
The inverse association between MRSA and MSSA point prevalence and minimal association on admission prevalence suggest MSSA carriage may protect against MRSA acquisition in nursing homes. The minimal association on admission prevalence further suggests competition may occur during nursing home stays.
Infect Control Hosp Epidemiol 2014;35(10):1257–1262
Central line-associated bloodstream infection (CLABSI) is a national target for mandatory reporting and a Centers for Medicare and Medicaid Services target for value-based purchasing. Differences in chart review versus claims-based metrics used by national agencies and groups raise concerns about the validity of these measures.
Evaluate consistency and reasons for discordance among chart review and claims-based CLABSI events.
We conducted 2 multicenter retrospective cohort studies within 6 academic institutions. A total of 150 consecutive patients were identified with CLABSI on the basis of National Healthcare Safety Network (NHSN) criteria (NHSN cohort), and an additional 150 consecutive patients were identified with CLABSI on the basis of claims codes (claims cohort). Ail events had full-text medical record reviews and were identified as concordant or discordant with the other metric.
In the NHSN cohort, there were 152 CLABSIs among 150 patients, and 73.0% of these cases were discordant with claims data. Common reasons for the lack of associated claims codes included coding omission and lack of physician documentation of bacteremia cause. In the claims cohort, there were 150 CLABSIs among 150 patients, and 65.3% of these cases were discordant with NHSN criteria. Common reasons for the lack of NHSN reporting were identification of non-CLABSI with bacteremia meeting Centers for Disease Control and Prevention (CDC) criteria for an alternative infection source.
Substantial discordance between NHSN and claims-based CLABSI indicators persists. Compared with standardized CDC chart review criteria, claims data often had both coding omissions and misclassification of non-CLABSI infections as CLABSI. Additionally, claims did not identify any additional CLABSIs for CDC reporting. NHSN criteria are a more consistent interhospital standard for CLABSI reporting.
Asymmetric (10L) XRD peaks have been employed as a measure of epitaxial quality for aluminum nitride (AlN) nucleation layers (NL) deposited on sapphire substrate. Epitaxial AlN films have been deposited on 2-6” sapphire substrate by reactive sputtering. FWHM of AlN (103) and (105) were found to be an excellent indicator of quality of AlN films for GaN growth. AlN films produced nucleation layers with highly reproducible microstructure and GaN film growth. NLs had in-plane and out-of-plane texture as evident by the pole-figure results and selected area diffraction pattern. Based on electron microscopy results, AlN film thickness for complete atomic ordering was estimated to be 6-7 nm and most of the edge dislocations were seen in the first 20 nm of the film. Excellent thickness and texture uniformity were seen on planar and patterned sapphire substrates. A compressive stress of 2.9±0.2 GPa was seen in our BKM films. The maximum screw and edge dislocation densities of films were found to be ∼3 x 108 cm−2 and ∼9 x 109 cm−2 respectively. The root mean square roughnesses of A-polar films were found to be < 0.3 nm.
We calculated hospital-onset methicillin-resistant Staphylococcus aureus (HO-MRSA) rates for Orange County, California, hospitals using survey and state data. Numerators were variably defined as HO-MRSA occurring more than 48 hours (37%), more than 2 days (30%), and more than 3 days (33%) postadmission. Survey-reported denominators differed from state-reported patient-days. Numerator and denominator choices substantially impacted HO-MRSA rates.
A buffalo oocyte-specific subtracted cDNA library was constructed to identify exclusively or preferentially oocyte-expressed genes. The library represented an enriched population of transcripts obtained from oocytes of diverse ovarian follicular origin and at different stages of in vitro maturation. A total of 1173 high-quality sequences of oocyte-specific genes were clustered into 645 unique sequences, out of which 65.76% were represented as singlets and 34.26% as contig expressed sequence tags (ESTs; clusters). Analysis of sequences revealed that 498 of these sequences were identified as a known sequence in mammalian species including buffalo, 103 as uncharacterized ESTs and 44 unknown sequences including 1 novel EST, so far not reported in any species. Gene ontology annotation classified these sequences into functional categories of cellular events and biological processes associated with oocyte competence. Expression status of the isolated unknown ESTs confirmed that many of these are expressed in oocytes exclusively and in others preferentially, some in excess of 80-fold greater in comparison with a variety of somatic tissues. The isolated novel EST was detected to be expressed exclusively in oocytes and testicular cells only. To our knowledge, this is the first report giving a detailed transcriptome account of oocyte-expressed genes in buffalo. This study will provide important information on the physiological control of oocyte development, as well as many questions yet to be addressed on the reproductive process of buffalo.
A nonlinear optical crystal of L-valine was grown from an aqueous solution containing a small amount of phosphoric acid by the slow evaporation method. The grown crystal was characterized by a single crystal X-ray diffraction to determine the unit cell parameters. The powder X-ray diffraction analysis also confirmed the lattice parameters to be a = 9.6687(7) Å, b = 5.2709(4) Å, c = 12.0371(10) Å and β = 90.805(4)°. The results of the Inductively Coupled Plasma Optical Emission Spectrometry (ICPOES) indicate the presence of a small amount of phosphorus in the grown crystal. The Vickers micro hardness test was performed to study the mechanical strength of the crystals. Chemical etching studies were carried out to analyze the dislocation structure. The laser damaged threshold of the grown crystal was measured to be 11.11 GW/cm2 for 10 ns pulse at 1064 nm, which is higher than that of the standard nonlinear optical crystals like KDP. Second harmonic generation of the grown crystals was also 1.44 times that of KDP.