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The denitrification process, namely the reduction of nitrate (NO3-) to nitrogen gas (N2), often cannot be simply modelled as a single step process. For a more complete and comprehensive model the intermediates, particularly nitrite (NO23) and nitrous oxide (N2O), need to be investigated. This paper demonstrates the integration of titrimetric measurements and off-gas analysis with on-line nitrite plus nitrate (NOx-) biosensors, highlighting the necessity of measuring process intermediates with high time-scale resolution to study and understand the kinetics of denitrification. Investigation of activated sludge from a full-scale treatment plant showed a significant accumulation of NO2-, which appeared to impact on the overall denitrification rate measured as NOx- reduction or N2 production. A different sludge obtained from a lab-scale bioreactor produced N2O instead of N2 as the end product of denitrification. The two examples both illustrate the complexity of denitrification and stress the need for the more versatile and detailed measurement procedures, as presented in this paper. [ABSTRACT FROM AUTHOR]

The denitrification process, namely the reduction of nitrate (NO3-) to nitrogen gas (N2), often cannot be simply modelled as a single step process. For a more complete and comprehensive model the intermediates, particularly nitrite (NO2-) and nitrous oxide (N2O), need to be investigated. This paper demonstrates the integration of titrimetric measurements and off-gas analysis with on-line nitrite plus nitrate (NOx-) biosensors, highlighting the necessity of measuring process intermediates with high time-scale resolution to study and understand the kinetics of denitrification. Investigation of activated sludge from a full-scale treatment plant showed a significant accumulation of NO2-, which appeared to impact on the overall denitrification rate measured as NOx- reduction or N2 production. A different sludge obtained from a lab-scale bioreactor produced N2O instead of N2 as the end product of denitrification. The two examples both illustrate the complexity of denitrification and stress the need for the more versatile and detailed measurement procedures, as presented in this paper. [ABSTRACT FROM AUTHOR]

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010. [ABSTRACT FROM PUBLISHER]

Construction activities may affect adjacent water systems by introducing increased levels of suspended solids into the water body and may subsequently affect the survival and growth of freshwater mussels. We tested three sediment types from sites in Missouri, including Spring River sediment (SRS), Osage River bank clay soil (ORC), and quarried limestone from Columbia (LMT). We prepared series of suspensions of each sediment with total suspended solids concentrations ranging from 0 to 5000 mg/L. Juveniles from three mussel species, Fatmucket (Lampsilis siliquoidea), Arkansas Brokenray (Lampsilis reeveiana), and Washboard (Megalonaias nervosa) were exposed to these suspensions in both acute (96-h) and chronic (28-d) tests. No clear impact on survival was observed from the acute or chronic exposures, but chronic test showed that juvenile mussels' growth was strongly affected. Interestingly, growth was enhanced at lower levels of SRS and ORC (≤500 mg/L, p < 0.05), and the juvenile mussels exposed to 500 mg/L SRS exhibited approximately 60 % more dry weight than those reared in the control. LMT did not enhance growth. Growth was slowed by high concentrations (>1000 mg/L) of all three sediments, implying that high suspended solids levels could reduce survival in the long term. Our findings may help to inform regulations and guidelines for construction activities to minimize adverse effects on juvenile mussels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The US Geological Survey. Published by Elsevier B.V. All rights reserved.)

Background: The blood pressure (BP) regulatory impact of the arterial baroreflex has been well established in health and disease. Under normotensive conditions, we have previously demonstrated functional differences in the central processing of the left versus right aortic baroreceptor afferent input. However, it is unknown if lateralization in aortic baroreflex function remains evident during hypertension., Method: We therefore, investigated the effects of laterality on the expression of baroreflex-driven cardiovascular reflexes in a genetic model of essential hypertension, the spontaneously hypertensive rat (SHR). Anesthetized male SHRs (total n  = 9) were instrumented for left, right, and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, and 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR), and femoral vascular resistance (FVR)., Results: Left right, and bilateral ADN stimulation evoked frequency-dependent decreases in MAP, HR, MVR, and FVR. Left and bilateral ADN stimulation evoked greater reflex reductions in MAP, HR, MVR, and FVR compared with right-sided stimulation. Reflex bradycardia to bilateral stimulation was larger relative to both left-sided and right-sided stimulation. Reflex depressor and vascular resistance responses to bilateral stimulation mimicked those of the left-sided stimulation. These data indicate a left-side dominance in the central integration of aortic baroreceptor afferent input. Furthermore, reflex summation due to bilateral stimulation is only evident on the reflex bradycardic response, and does not drive further reductions in BP, suggesting that reflex depressor responses in the SHRs are primarily driven by changes in vascular resistance., Conclusion: Together, these results indicate that lateralization in aortic baroreflex function is not only evident under normotensive conditions but also extends to hypertensive conditions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Software Defect Prediction (SDP) is an integral aspect of the Software Development Life-Cycle (SDLC). As the prevalence of software systems increases and becomes more integrated into our daily lives, so the complexity of these systems increases the risks of widespread defects. With reliance on these systems increasing, the ability to accurately identify a defective model using Machine Learning (ML) has been overlooked and less addressed. Thus, this article contributes an investigation of various ML techniques for SDP. An investigation, comparative analysis and recommendation of appropriate Feature Extraction (FE) techniques, Principal Component Analysis (PCA), Partial Least Squares Regression (PLS), Feature Selection (FS) techniques, Fisher score, Recursive Feature Elimination (RFE), and Elastic Net are presented. Validation of the following techniques, both separately and in combination with ML algorithms, is performed: Support Vector Machine (SVM), Logistic Regression (LR), Naïve Bayes (NB), K-Nearest Neighbour (KNN), Multilayer Perceptron (MLP), Decision Tree (DT), and ensemble learning methods Bootstrap Aggregation (Bagging), Adaptive Boosting (AdaBoost), Extreme Gradient Boosting (XGBoost), Random Forest(RF), and Generalized Stacking (Stacking). Extensive experimental setup was built and the results of the experiments revealed that FE and FS can both positively and negatively affect performance over the base model or Baseline. PLS, both separately and in combination with FS techniques, provides impressive, and the most consistent, improvements, while PCA, in combination with Elastic-Net, shows acceptable improvement.

Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for potential translation into the clinic. Published studies have used supramaximal stimulations, which are unphysiological and energy inefficient. The objective of the present study was to identify optimal low-charge nerve stimulation parameters that would provide a clinically-relevant (20-30 mmHg) decrease in mean arterial pressure (MAP) in anesthetized spontaneously hypertensive rats. Stimulations of 20 s were delivered to the left aortic depressor nerve (ADN) of these rats using low ranges of pulse amplitudes (≤ 0.6 mA), widths (≤ 0.5 ms) and frequencies (≤ 5 Hz). We also assessed the effects of continuous (20 s) versus intermittent (5 s ON/3 s OFF and 5 s ON/3 s OFF for 20 s) stimulation on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance using low (5 Hz) and high (15 Hz) frequencies. Lower pulse amplitudes (0.2 mA) produced 9 ± 2 to 18 ± 2 mmHg decreases in MAP. Higher pulse amplitudes (0.4 mA) produced a median MAP reduction of 28 ± 4 mmHg at 0.2 ms and 5 Hz, with no added benefit seen above 0.4 mA. Continuous and intermittent low frequency stimulation at 0.4 mA and 0.2 ms produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation at 0.4 mA and 0.2 ms produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. We conclude from these findings that "low intensity intermittent" electrical stimulation is an effective alternate way for neuromodulation of the aortic baroreceptor afferents and to evoke a required restoration of MAP levels in spontaneously hypertensive rats. This approach enables low energy consumption and markedly lowers the excessive decreases in MAP and hemodynamic disturbances elicited by continuous high-charge injection protocols., (© 2022. The Author(s).)

Abstract: Nav1.7 is a promising drug target for the treatment of pain. However, there is a mismatch between the analgesia produced by Nav1.7 loss-of-function and the peripherally restricted Nav1.7 inhibitors, which may reflect a lack of understanding of the function of Nav1.7 in the transmission of nociceptive information. In the periphery, the role of Nav1.7 in transduction at nociceptive peripheral terminals has been comprehensively examined, but its role in axonal propagation in these neurons is less clearly defined. In this study, we examined the contribution of Nav1.7 to axonal propagation in nociceptors using sodium channel blockers in in vivo electrophysiological and calcium imaging recordings in mice. Using the sodium channel blocker tetrodotoxin (TTX) (1-10 µM) to inhibit Nav1.7 and other tetrodotoxin-sensitive sodium channels along the sciatic nerve, we first showed that around two-thirds of nociceptive L4 dorsal root ganglion neurons innervating the skin, but a lower proportion innervating the muscle (45%), are blocked by TTX. By contrast, nearly all large-sized cutaneous afferents (95%-100%) were blocked by axonal TTX. Many cutaneous nociceptors resistant to TTX were polymodal (57%) and capsaicin sensitive (57%). Next, we applied PF-05198007 (300 nM-1 µM) to the sciatic nerve between stimulating and recording sites to selectively block axonal Nav1.7 channels. One hundred to three hundred nanomolar PF-05198007 blocked propagation in 63% of C-fiber sensory neurons, whereas similar concentrations produced minimal block (5%) in rapidly conducting A-fiber neurons. We conclude that Nav1.7 is essential for axonal propagation in around two-thirds of nociceptive cutaneous C-fiber neurons and a lower proportion (≤45%) of nociceptive neurons innervating muscle., (Copyright © 2021 International Association for the Study of Pain.)

Background: Local recurrence rates (LRRs) after Mohs micrographic surgery (MMS) for male genital cancers have been reported in only a few small case series, and patient-reported outcomes (PROs) have not been studied., Objective: To determine the LRR and PROs after MMS for male genital skin cancers., Methods: Retrospective review of all male genital skin cancers removed with MMS between 2008 and 2019 at an academic center. LRR was determined by chart review and phone calls. PROs were assessed by survey., Results: A total of 119 skin cancers in 108 patients were removed with MMS. Tumors were located on the penis (90/119) and scrotum (29/119). Diagnoses included squamous cell carcinoma in situ (n = 71), invasive squamous cell carcinoma (n = 32), extramammary Paget disease (n = 13), melanoma (n = 2), and basal cell carcinoma (n = 1). The LRR was 0.84% (1/119), with a mean follow-up time of 3.25 years (median, 2.36 years). The majority of survey respondents reported no changes in urinary (66%) or sexual functioning (57.5%) after surgery., Limitations: Retrospective single-center experience; short follow-up time; low survey response rate; no baseline functional data., Conclusion: MMS for male genital skin cancer has a low LRR and high patient-reported satisfaction with urinary and sexual function., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020. Published by Elsevier Inc.)

Importance: While several studies have demonstrated the benefit of enrollment in chronic condition special needs plans (C-SNPs) for other chronic diseases (eg, diabetes), there is no evaluation of the association of C-SNPs with outcomes among patients with end-stage kidney disease (ESKD)., Objective: To examine whether and to what degree C-SNP enrollment was associated with improved clinical outcomes and quality of life in patients with ESKD., Design, Setting, and Participants: This multicenter cohort study included 2718 patients who were newly enrolled in an ESKD C-SNP between January 1, 2013, and September 30, 2017, and receiving dialysis from DaVita Kidney Care. Patients were followed up until death, loss to follow-up, or end of study (ie, December 31, 2018). Enrollees in C-SNP were matched via multiple clinical and demographic characteristics with 2 different control populations, as follows: (1) those in the same facilities (n = 2545) or (2) those in similar counties (n = 1986). Patients enrolled in CareMore C-SNPs (n = 206) were excluded from the study. Data analysis was conducted June to December 2019., Exposures: Standard ESKD care with dialysis plus access to an integrated care team who worked with the patient and the dialysis team, comprehensive health assessments done by the integrated care team, and access to select benefits (such as vision and dental care) as a C-SNP enrollee., Main Outcomes and Measures: Hospitalizations, mortality, laboratory values indicative of metabolic control, and Kidney Disease Quality of Life 36-item (KDQOL-36) survey scores., Results: The 2545 C-SNP enrollees in the facility-matched analysis had a mean (SD) age of 57.2 (12.9) years, and included 968 (38.0%) women, 1328 (52.2%) Hispanic individuals, and 553 (21.7%) African American individuals. The 1986 C-SNP enrollees in the county-matched analysis had a mean (SD) age of 57.8 (12.2) years, with 705 (35.5%) women, 1085 (54.6%) Hispanic individuals, and 472 (23.8%) African American individuals. Compared with patients not enrolled in C-SNP, enrollees had lower hospitalization rates, with incidence rate ratios of 0.90 (95% CI, 0.84-0.97; P = .006) in the facility-matched analysis and 0.76 (95% CI, 0.70-0.83; P < .001) in the county-matched analysis. Compared with patients not enrolled in C-SNP, enrollees had decreased mortality risk in the same facilities (hazard ratio, 0.77; 95% CI, 0.68-0.88; P < .001) and in the same counties (hazard ratio, 0.77; 95% CI, 0.66-0.88; P < .001). No significant differences were observed between C-SNP enrollees and matched patients in metabolic laboratory values or KDQOL-36 survey scores., Conclusions and Relevance: This cohort study found a positive association of C-SNP enrollment with lower rates of hospitalization and mortality. The findings suggest that the additional services and benefits C-SNPs provide may improve outcomes compared with standard of care for patients with ESKD.

This paper considers samples of independent writing highlighting the integral role of phonology, orthography and morphology in spelling development for children from 5-6 years to 7-8 years (3 years of formal schooling). It also introduces an approach to monitoring spelling development by considering the sources of knowledge that are evident in children's attempts to spell when writing independently. Synthetic phonics can be a powerful and effective strategy for both reading and spelling; however when the development of a synthetic phonics strategy fails to take account of the importance of compatibility with orthographic and morphemic knowledge its predominant use can lead to long term spelling difficulties for children who cannot acquire this knowledge from implicit learning when reading. Furthermore, this paper proposes that there may be an optimum period for ensuring the interaction between phonemic, orthographic and morphemic knowledge (5-6 years to 7-8 years; 3 years of formal schooling) during which time significant gains can be made for all children. This optimum period is particularly important for children who are at risk of long-term spelling difficulties because they spell by sounds alone as a result of insensitivity to orthographic and ortho-morphemic patterns., (© 2020 John Wiley & Sons Ltd.)

We explored the effects of baroreceptor afferents laterality and sexual dimorphism on the expression of cardiovascular reflex responses to baroreflex activation in Sprague Dawley (SD) rats. Under urethane anesthesia, rats of either sex (total n = 18) were instrumented for left, right and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR) and mesenteric (MVR) and femoral (FVR) vascular resistance. Female rats were matched for the diestrus phase of the estrus cycle. Left, right and bilateral ADN stimulation evoked frequency-dependent drops in MAP, HR, and MVR, and increases in FVR. Irrespective of sex, left and bilateral ADN stimulation as compared to right-sided stimulation mediated greater reflex reductions in MAP, HR, and MVR but not in FVR. In males, reflex bradycardic responses were greater in response to bilateral stimulation relative to both left- and right-sided stimulation. In females, left ADN stimulation evoked the largest increase in FVR. Left and bilateral ADN stimulations evoked greater reductions in MAP and MVR while left-sided stimulation produced larger increases in FVR in females compared with males. All other reflex responses to ADN stimulation were relatively comparable between males and females. These results show a differential baroreflex processing of afferent neurotransmission promoted by left versus right baroreceptor afferent inputs and sexual dimorphism in the expression of baroreflex responses in rats of either sex. Collectively, these data add to our understanding of physiological mechanisms pertaining to baroreflex control in both males and females., (Copyright © 2020 Salman, Ameer, McMurray, Giarola, Sridhar, Lewis and Hsieh.)

The role of brain-derived neurotrophic factor (BDNF) signaling in chronic pain has been well documented. Given the important central role of BDNF in long term plasticity and memory, we sought to engineer a high affinity, peripherally-restricted monoclonal antibody against BDNF to modulate pain. BDNF shares 100% sequence homology across human and rodents; thus, we selected chickens as an alternative immune host for initial antibody generation. Here, we describe the affinity optimization of complementarity-determining region-grafted, chicken-derived R3bH01, an anti-BDNF antibody specifically blocking the TrkB receptor interaction. Antibody optimization led to the identification of B30, which has a > 300-fold improvement in affinity based on BIAcore, an 800-fold improvement in potency in a cell-based pERK assay and demonstrates exquisite selectivity over related neurotrophins. Affinity improvements measured in vitro translated to in vivo pharmacological activity, with B30 demonstrating a 30-fold improvement in potency over parental R3bH01 in a peripheral nerve injury model. We further demonstrate that peripheral BDNF plays a role in maintaining the plasticity of sensory neurons following nerve damage, with B30 reversing neuron hyperexcitability associated with heat and mechanical stimuli in a dose-dependent fashion. In summary, our data demonstrate that effective sequestration of BDNF via a high affinity neutralizing antibody has potential utility in modulating the pathophysiological mechanisms that drive chronic pain states.

Objectives: Patients with end-stage renal disease (ESRD) are clinically complex, requiring intensive and costly care. Coordinated care may improve outcomes and reduce costs. The objective of this study was to determine the impact of a payer-provider care partnership on key clinical and economic outcomes in enrolled patients with ESRD., Study Design: Retrospective observational study., Methods: Data on patient demographics and clinical outcomes were abstracted from the electronic health records of the dialysis provider. Data on healthcare costs were collected from payer claims. Data were collected for a baseline period prior to initiation of the partnership (July 2011-June 2012) and for two 12-month periods following initiation (April 2013-March 2014 and April 2014-March 2015)., Results: Among both Medicare Advantage and commercial insurance program members, the rate of central venous catheter use for vascular access was lower following initiation of the partnership compared with the baseline period. Likewise, hospital admission rates, emergency department visit rates, and readmission rates were lower following partnership initiation. Rates of influenza and pneumococcal vaccination were higher than 95% throughout all 3 time periods. Total medical costs were lower for both cohorts of members in the second 12-month period following partnership initiation compared with the baseline period., Conclusions: Promising trends were observed among members participating in this payer-provider care partnership with respect to both clinical and economic outcomes. This suggests that collaborations with shared incentives may be a valuable approach for patients with ESRD.

This paper considers two major concerns centring on the Joint Council for Qualifications (JCQ) regulations for access arrangement and reasonable adjustments and qualifications for teachers who take on the role of Level 7 access arrangements assessor. Thus, the paper is divided into two parts. First, the JCQ 2017-2018 regulations are critically evaluated highlighting the areas of need for which greater clarity and more extensive detail is required in these regulations. The second part of the paper discusses the findings of research on teacher competence in test administration, scoring, and reporting. Drawing on evidence from the first stage of this research, McMurray, O'Callaghan, and McVeigh highlight the extensive formative process required to build a high-level skill set required for competent assessment involving the use of high level tests and also the specialist knowledge required to analyse and accurately report assessment findings to make recommendations for students with specific literacy difficulties. Recommendations are provided both at policy and practice levels regarding the content of courses and the assessment involving the use of high level tests and also the specialist knowledge required to analyse and accurately report assessment findings to make recommendations for students with specific literacy difficulties. The authors provide recommendations for test publishers, course providers, and assessors., (Copyright © 2018 John Wiley & Sons, Ltd.)

Women suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. In this study we used a mouse model of neuropathic pain to dissociate these factors. We performed RNA-seq on purified peripheral afferent neurons, but found no striking differences in gene expression between male and female mice, neither before nor after nerve injury. Similarly, spinal cord immune responses between the sexes appeared to be indistinguishable when studied by flow cytometry or qRT-PCR. Differences emerged only upon studying peripheral immune cell infiltration into the dorsal root ganglion, suggesting that adaptive immune responses in neuropathic pain could be sexually dimorphic.