Language and developmental plasticity after perinatal stroke.

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

One right can make a left: sentence processing in the right hemisphere after perinatal stroke.

When brain regions that are critical for a cognitive function in adulthood are irreversibly damaged at birth, what patterns of plasticity support the successful development of that function in an alternative location? Here we investigate the consistency of language organization in the right hemisphere (RH) after a left hemisphere (LH) perinatal stroke. We analyzed fMRI data collected during an auditory sentence comprehension task on 14 people with large cortical LH perinatal arterial ischemic strokes (left hemisphere perinatal stroke (LHPS) participants) and 11 healthy sibling controls using a "top voxel" approach that allowed us to compare the same number of active voxels across each participant and in each hemisphere for controls. We found (1) LHPS participants consistently recruited the same RH areas that were a mirror-image of typical LH areas, and (2) the RH areas recruited in LHPS participants aligned better with the strongly activated LH areas of the typically developed brains of control participants (when flipped images were compared) than the weakly activated RH areas. Our findings suggest that the successful development of language processing in the RH after a LH perinatal stroke may in part depend on recruiting an arrangement of frontotemporal areas reflective of the typical dominant LH.

Reproducibility and Relative Validity of a Dietary Screener Adapted for Use among Pregnant Women in Dhulikhel, Nepal.

OBJECTIVES: Here we examined the reproducibility and validity of a dietary screener which was translated and adapted to assess diet quality among pregnant Nepalese women. METHODS: A pilot cohort of singleton pregnant women (N = 101; age 25.9 ± 4.1 years) was recruited from a tertiary, periurban hospital in Nepal. An adapted Nepali version of the PrimeScreen questionnaire, a brief 21-item dietary screener that assesses weekly consumption of 12 healthy and 9 unhealthy food groups, was administered twice, and a month apart, in both the 2nd and 3rd trimesters. Up to four inconsecutive 24-h dietary recalls (24-HDRs) were completed each trimester and utilized as the reference method for validation. For each trimester, data from multiple 24-HDRs were averaged across days, and items were grouped to match the classification and three weekly consumption categories (0-1, 2-3, or 4 + servings/week) of the 21 food groups represented on the PrimeScreen. RESULTS: Gwet's agreement coefficients (AC1) were used to evaluate the reproducibility and validity of the adapted PrimeScreen against the 24-HDRs in both the 2nd and 3rd trimester. AC1 indicated good to excellent (≥ 0.6) reproducibility for the majority (85%) of food groups across trimesters. There was moderate to excellent validity (AC1 ≥ 0.4) for all food groups except for fruits and vegetables in the 2nd trimester, and green leafy vegetables and eggs in both the 2nd and 3rd trimesters. CONCLUSIONS: The modified PrimeScreen questionnaire appears to be a reasonably valid and reliable instrument for assessing the dietary intake of most food groups among pregnant women in Nepal.

Cadherin 11 Promotes Immunosuppression and Extracellular Matrix Deposition to Support Growth of Pancreatic Tumors and Resistance to Gemcitabine in Mice.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDACs) are characterized by fibrosis and an abundance of cancer-associated fibroblasts (CAFs). We investigated strategies to disrupt interactions among CAFs, the immune system, and cancer cells, focusing on adhesion molecule CDH11, which has been associated with other fibrotic disorders and is expressed by activated fibroblasts. METHODS: We compared levels of CDH11 messenger RNA in human pancreatitis and pancreatic cancer tissues and cells with normal pancreas, and measured levels of CDH11 protein in human and mouse pancreatic lesions and normal tissues. We crossed p48-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ (KPC) mice with CDH11-knockout mice and measured survival times of offspring. Pancreata were collected and analyzed by histology, immunohistochemistry, and (single-cell) RNA sequencing; RNA and proteins were identified by imaging mass cytometry. Some mice were given injections of PD1 antibody or gemcitabine and survival was monitored. Pancreatic cancer cells from KPC mice were subcutaneously injected into Cdh11+/+ and Cdh11-/- mice and tumor growth was monitored. Pancreatic cancer cells (mT3) from KPC mice (C57BL/6), were subcutaneously injected into Cdh11+/+ (C57BL/6J) mice and mice were given injections of antibody against CDH11, gemcitabine, or small molecule inhibitor of CDH11 (SD133) and tumor growth was monitored. RESULTS: Levels of CDH11 messenger RNA and protein were significantly higher in CAFs than in pancreatic cancer epithelial cells, human or mouse pancreatic cancer cell lines, or immune cells. KPC/Cdh11+/- and KPC/Cdh11-/- mice survived significantly longer than KPC/Cdh11+/+ mice. Markers of stromal activation entirely surrounded pancreatic intraepithelial neoplasias in KPC/Cdh11+/+ mice and incompletely in KPC/Cdh11+/- and KPC/Cdh11-/- mice, whose lesions also contained fewer FOXP3+ cells in the tumor center. Compared with pancreatic tumors in KPC/Cdh11+/+ mice, tumors of KPC/Cdh11+/- mice had increased markers of antigen processing and presentation; more lymphocytes and associated cytokines; decreased extracellular matrix components; and reductions in markers and cytokines associated with immunosuppression. Administration of the PD1 antibody did not prolong survival of KPC mice with 0, 1, or 2 alleles of Cdh11. Gemcitabine extended survival of KPC/Cdh11+/- and KPC/Cdh11-/- mice only or reduced subcutaneous tumor growth in mT3 engrafted Cdh11+/+ mice when given in combination with the CDH11 antibody. A small molecule inhibitor of CDH11 reduced growth of pre-established mT3 subcutaneous tumors only if T and B cells were present in mice. CONCLUSIONS: Knockout or inhibition of CDH11, which is expressed by CAFs in the pancreatic tumor stroma, reduces growth of pancreatic tumors, increases their response to gemcitabine, and significantly extends survival of mice. CDH11 promotes immunosuppression and extracellular matrix deposition, and might be developed as a therapeutic target for pancreatic cancer.

Digital technologies: tensions in privacy and data.

Driven by data proliferation, digital technologies have transformed the marketing landscape. In parallel, significant privacy concerns have shaken consumer-firm relationships, prompting changes in both regulatory interventions and people's own privacy-protective behaviors. With a comprehensive analysis of digital technologies and data strategy informed by structuration theory and privacy literature, the authors consider privacy tensions as the product of firm-consumer interactions, facilitated by digital technologies. This perspective in turn implies distinct consumer, regulatory, and firm responses related to data protection. By consolidating various perspectives, the authors propose three tenets and seven propositions, supported by interview insights from senior managers and consumer informants, that create a foundation for understanding the digital technology implications for firm performance in contexts marked by growing privacy worries and legal ramifications. On the basis of this conceptual framework, they also propose a data strategy typology across two main strategic functions of digital technologies: data monetization and data sharing. The result is four distinct types of firms, which engage in disparate behaviors in the broader ecosystem pertaining to privacy issues. This article also provides directions for research, according to a synthesis of findings from both academic and practical perspectives.

Ventilator-Weaning Pathway Associated With Decreased Ventilator Days in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: There is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors. DESIGN: Secondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days. SETTING: Large academic tertiary-care PICU. PATIENTS: Children with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation. INTERVENTIONS: Implementation of a ventilator-weaning pathway on May 2016. MEASUREMENTS AND MAIN RESULTS: Of 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders. CONCLUSIONS: Ventilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas.

PURPOSE: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. METHODS: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. RESULTS: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. CONCLUSIONS: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

Mobile Remote Monitoring of Intimate Partner Violence Among Pregnant Patients During the COVID-19 Shelter-In-Place Order: Quality Improvement Pilot Study.

BACKGROUND: Intimate partner violence (IPV) is one of the leading causes of pregnancy-related death. Prenatal health care providers can offer critical screening and support to pregnant people who experience IPV. During the COVID-19 shelter-in-place order, mobile apps may offer such people the opportunity to continue receiving screening and support services. OBJECTIVE: We aimed to examine cases of IPV that were reported on a prenatal care app before and during the implementation of COVID-19 shelter-in-place mandates. METHODS: The number of patients who underwent voluntary IPV screening and the incidence rate of IPV were determined by using a prenatal care app that was disseminated to patients from a single, large health care system. We compared the IPV screening frequencies and IPV incidence rates of patients who started using the app before the COVID-19 shelter-in-place order, to those of patients who started using the app during the shelter-in-place order. RESULTS: We found 552 patients who started using the app within 60 days prior to the enforcement of the shelter-in-place order, and 407 patients who used the app at the start of shelter-in-place enforcement until the order was lifted. The incidence rates of voluntary IPV screening for new app users during the two time periods were similar (before sheltering in place: 252/552, 46%; during sheltering in place: 163/407, 40%). The overall use of the IPV screening tool increased during the shelter-in-place order. A slight, nonsignificant increase in the incidence of physical, sexual, and psychological violence during the shelter-in-place order was found across all app users (P=.56). Notably, none of the patients who screened positively for IPV had mentions of IPV in their medical charts. CONCLUSIONS: App-based screening for IPV is feasible during times when in-person access to health care providers is limited. Our results suggest that the incidence of IPV slightly increased during the shelter-in-place order. App-based screening may also address the needs of those who are unwilling or unable to share their IPV experiences with their health care provider.

Factors associated with biomedical research participation within community-based samples across 3 National Cancer Institute-designated cancer centers.

BACKGROUND: Engaging diverse populations in biomedical research, including biospecimen donation, remains a national challenge. This study examined factors associated with an invitation to participate in biomedical research, intent to participate in biomedical research in the future, and participation in biomedical research and biospecimen donation among a diverse, multilingual, community-based sample across 3 distinct geographic areas. METHODS: Three National Cancer Institute-designated cancer centers engaged in community partnerships to develop and implement population health assessments, reaching a convenience sample of 4343 participants spanning their respective catchment areas. Data harmonization, multiple imputation, and multivariable logistic modeling were used. RESULTS: African Americans, Hispanic/Latinos, and other racial minority groups were more likely to be offered opportunities to participate in biomedical research compared to whites. Access to care, history of cancer, educational level, survey language, nativity, and rural residence also influenced opportunity, intent, and actual participation in biomedical research. CONCLUSIONS: Traditionally underserved racial and ethnic groups reported heightened opportunity and interest in participating in biomedical research. Well-established community partnerships and long-standing community engagement around biomedical research led to a diverse sample being reached at each site and may in part explain the current study findings. However, this study illustrates an ongoing need to establish trust and diversify biomedical research participation through innovative and tailored approaches. National Cancer Institute-designated cancer centers have the potential to increase opportunities for diverse participation in biomedical research through community partnerships and engagement. Additional work remains to identify and address system-level and individual-level barriers to participation in both clinical trials and biospecimen donation for research.

Walking Gait Mechanics and Gaze Fixation in Individuals With Chronic Ankle Instability.

CONTEXT: Many individuals who suffer a lateral ankle sprain will develop chronic ankle instability (CAI). Individuals with CAI demonstrate kinematic differences in walking gait, as well as somatosensory alterations compared with healthy individuals. However, the role of vision during walking gait in this population remains unclear. OBJECTIVE: To evaluate ankle kinematics, gaze deviations, and gaze velocity between participants with CAI and healthy controls while walking on a treadmill during 3 separate visual conditions (no target, fixed target, and moving target). DESIGN: Case-control study. SETTING: Laboratory. Patients (or Other Participants): Ten CAI participants and 10 healthy matched controls participated. MAIN OUTCOME MEASURES: Ankle sagittal and frontal plane kinematics were analyzed for the entire gait cycle. Average and standard deviation (SD) for gaze deviation and gaze velocity were calculated in the horizontal (X) and vertical (Y) planes. RESULTS: No significant differences were found between groups for either ankle kinematics or gaze variables; however, large effect sizes were found in the no target condition for average deviation of X (healthy 0.05 [0.02], CAI 0.12 [0.11]). Moderate effect sizes were identified in the no target condition for SD of Y (healthy 0.04 [0.03], CAI 0.11 [0.15]) and the moving target condition for average velocity of X (healthy 1.56 [0.73], CAI 2.27 [1.15]) and Y (healthy 1.07 [0.51], CAI 1.47 [0.52]). CONCLUSIONS: Although no significant differences were found between groups, it is possible that the role of vision in individuals with CAI may be altered with a more difficult task.

Satisfaction With Work-Family Balance Mediates the Relationship Between Workplace Social Support and Depression Among Hospice Nurses.

PURPOSE: The purpose of this study was to investigate the relationship between social support (from personal and workplace sources) and psychological distress (depression, anxiety, and stress symptoms), as well as to examine the mediating role of satisfaction with work-family balance among hospice nurses. DESIGN AND METHOD: A cross-sectional study design was utilized with a sample of 90 hospice nurses from the southern United States. Participants completed online surveys, including (a) the Depression, Anxiety, and Stress Scale (DASS-21), (b) loosely adapted items from the Affectivity, Burnout, and Absenteeism Scales, and (c) Satisfaction with Work-Family Balance Scale. FINDINGS: Workplace social support, not personal social support, was associated with lower psychological distress, and satisfaction with work-family balance mediated the relationship between workplace social support and depression symptoms, a component of psychological distress. CONCLUSIONS: Hospice nurses' social support in the workplace and their satisfaction with the balance between their work and family lives play a role in supporting their mental health. CLINICAL RELEVANCE: Hospice nurses may benefit from programs fostering the creation of workplace-based interpersonal relationships.

Femininity, masculinity, and body image in a community-based sample of lesbian and bisexual women.

This study expands the literature on body image among lesbian and bisexual women by examining the relationship between self-perceived gendered personality traits and expressions (i.e., sense of self in relation to cultural constructions of femininity and masculinity) and body satisfaction, a key body image construct. We used data from Wave 3 (2010-2012) of the Chicago Health and Life Experiences of Women (CHLEW) study. The CHLEW includes a novel measure of gender expression, with masculinity and femininity as distinct but overlapping constructs. In the large analytic sample (N = 553), we found both similarities and differences in the association between femininity/masculinity and body image in lesbian and bisexual women. Bisexual women reported significantly lower body satisfaction than lesbian women. Higher masculinity was associated with greater body satisfaction in the full sample, but the association was stronger for bisexual than lesbian women. Femininity was positively associated with body satisfaction only for bisexual women. These findings suggest that masculinity and femininity play different roles in body satisfaction for lesbian and bisexual women and highlight the importance of disaggregating sexual identity in studies of sexual minority women's health. Clinicians should routinely ask about sexual identity and gender expression, especially when presenting concerns involve body image or disordered eating.

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy.

Billing and Volunteers Substantially Reduced School-Located Influenza Vaccination Costs, 2 Oregon Counties, 2010-2011.

BACKGROUND AND OBJECTIVES: After the 2009 pandemic influenza seasons, the financial sustainability of school-located vaccination (SLV) clinics drew much attention. This study estimated and compared the labor costs of SLV clinics and reimbursements for influenza vaccinations for students attending 5 schools in 2 Oregon counties during 2010-2011. DESIGN/SETTING: Using a biweekly, Web-based survey, staff and volunteers prospectively tracked the time they spent on SLV clinic planning, implementation, and billing. They also tracked claims submitted and reimbursements by payment source. MAIN OUTCOME MEASURE: We report labor hours and associated costs for implementing school-based vaccination clinics; number of claims submitted and the reimbursement rate; and total and net costs. RESULTS: In county A, 260 doses were administered at a total cost of $5009 and received $3620 in payment. For county B, 165 doses were administered at a cost of $5598 and received $3807 in payments. With billing, the net cost per dose decreased from $19.74 to $8.57 and $38.08 to $16.17, for county A and county B, respectively. CONCLUSIONS: Reimbursements reduced cost per dose by 48% across SLV clinics across both Oregon counties. Local health departments can bill local health insurers to offset costs for implementing school-based vaccination clinics. Efforts to set up billing processes require dedicated billing staff who can effectively manage claims submission processes with multiple health insurers.

Brain white matter changes in CPAP-treated obstructive sleep apnea patients with residual sleepiness.

PURPOSE: To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence. MATERIALS AND METHODS: Twenty-nine male patients (30-55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of the magnetic resonance imaging (MRI) scan. Based on the PVT results, the patients were divided into a nonsleepy group (lapses ≤5) and a sleepy group (lapses >5). DTI was performed at 3T, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1 ), and radial diffusivity (λ23 ) between the two groups. RESULTS: A higher MD (P < 0.05) was observed in the sleepy group than the nonsleepy group in the whole-brain TBSS analysis in the WM. The increased MD (17.8% of the fiber tracts; P < 0.05) was caused primarily by an elevated λ23 . Axial diffusivity (λ1 ) exhibited no significant difference (P > 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, P < 0.05). CONCLUSION: Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes. Evidence level: 1 J. MAGN. RESON. IMAGING 2017;45:1371-1378.

VALIDATION OF ULTRASOUND AS A NONINVASIVE TOOL TO MEASURE SUBCUTANEOUS FAT DEPTH IN LEATHERBACK SEA TURTLES (DERMOCHELYS CORIACEA).

Leatherback turtles (Dermochelys coriacea) undergo substantial cyclical changes in body condition between foraging and nesting. Ultrasonography has been used to measure subcutaneous fat as an indicator of body condition in many species but has not been applied in sea turtles. To validate this technique in leatherback turtles, ultrasound images were obtained from 36 live-captured and dead-stranded immature and adult turtles from foraging and nesting areas in the Pacific and Atlantic oceans. Ultrasound measurements were compared with direct measurements from surgical biopsy or necropsy. Tissue architecture was confirmed histologically in a subset of turtles. The dorsal shoulder region provided the best site for differentiation of tissues. Maximum fat depth values with the front flipper in a neutral (45-90°) position demonstrated good correlation with direct measurements. Ultrasound-derived fat measurements may be used in the future for quantitative assessment of body condition as an index of health in this critically endangered species.

Assessing microbial competition in a hydrogen-based membrane biofilm reactor (MBfR) using multidimensional modeling.

The membrane biofilm reactor (MBfR) is a novel technology that safely delivers hydrogen to the base of a denitrifying biofilm via gas-supplying membranes. While hydrogen is an effective electron donor for denitrifying bacteria (DNB), it also supports sulfate-reducing bacteria (SRB) and methanogens (MET), which consume hydrogen and create undesirable by-products. SRB and MET are only competitive for hydrogen when local nitrate concentrations are low, therefore SRB and MET primarily grow near the base of the biofilm. In an MBfR, hydrogen concentrations are greatest at the base of the biofilm, making SRB and MET more likely to proliferate in an MBfR system than a conventional biofilm reactor. Modeling results showed that because of this, control of the hydrogen concentration via the intramembrane pressure was a key tool for limiting SRB and MET development. Another means is biofilm management, which supported both sloughing and erosive detachment. For the conditions simulated, maintaining thinner biofilms promoted higher denitrification fluxes and limited the presence of SRB and MET. The 2-d modeling showed that periodic biofilm sloughing helped control slow-growing SRB and MET. Moreover, the rough (non-flat) membrane assembly in the 2-d model provided a special niche for SRB and MET that was not represented in the 1-d model. This study compared 1-d and 2-d biofilm model applicability for simulating competition in counter-diffusional biofilms. Although more computationally expensive, the 2-d model captured important mechanisms unseen in the 1-d model.

Evaluation of a New Vancomycin Dosing Protocol in Morbidly Obese Patients.

BACKGROUND: Optimal dosing of vancomycin in morbidly obese patients (>100 kg and at least 140% of their ideal body weight) has not been determined. Conventional dosing strategies have led to the observation of supratherapeutic trough concentrations (>20 mcg/mL). OBJECTIVE: To evaluate the effectiveness of a new vancomycin dosing protocol in morbidly obese patients in achieving therapeutic trough concentrations between 10 and 20 mcg/mL and to determine patient-specific factors influencing the trough concentration attained. METHODOLOGY: A single-center, retrospective chart review included morbidly obese adult patients with a pharmacy-to-dose vancomycin consult and at least 1 trough concentration obtained at steady state. Patients were excluded if they had a creatinine clearance (CrCl) less than 35 mL/min or unstable renal function, were not dosed according to the revised protocol, or received vancomycin prior to initiation of the protocol. RESULTS: Of the 48 patients included, 17 (35.4%) achieved a therapeutic vancomycin trough concentration. Subtherapeutic concentrations (<10 mcg/mL) were observed in 27 patients (56.3%) and supratherapeutic concentrations were observed in 4 (8.3%) patients. Age less than 45 years and CrCl greater than 100 mL/min were associated with subtherapeutic trough concentrations. CONCLUSION: This study demonstrates that the revised vancomycin dosing protocol led to the attainment of therapeutic trough concentrations in 35.4% of patients. The majority had subtherapeutic concentrations, which increases the risk of treatment failures and resistance. Further study is needed to determine the optimal dosing strategy in this patient population.