Improvements to the analytical performance of ion trap mass spectrometry

Mass spectrometry is a powerful analytical technique that is capable of a wide range of chemical and biological analyses. The quadrupole ion trap mass spectrometer (QITMS) is known for its ruggedness, sensitivity, and high efficiency for tandem mass spectrometry (MS/MS) experiments. Non-idealities in electrode geometry result in small contributions of higher order fields (HOFs) to the primary quadrupolar electric field of the ion trap. These HOFs have been useful in enhancing the resolution, MS/MS efficiency, and sensitivity in the QITMS. A portion of the work presented in this dissertation is intended to serve as a basis for improved ion trap performance through the judicious use of HOFs. Development of rf circuitry and characterization of a compensated cylindrical ion trap (CCIT) mass spectrometer, designed for studying the effects of HOFs, are also described herein. An additional set of grounded electrodes was introduced into the CCIT instrument to remove detrimental effects of capacitive coupling and HOFs were successfully introduced. Mass spectra acquired after the introduction of HOFs showed improvements to the injection efficiency over a broad range of rf voltages. The optimal conditions for resonance ejection in the CCIT occurred at an octapole HOF non-linear resonance, which gave improvements both to mass resolution and sensitivity (i.e., the number of ions detected). Resonance ejection performed at an octapole non-linear resonance was successful in improving the sensitivity of the CCIT for the analysis of volatile organic compounds in the presence of a heavy buffer gas. A novel higher order field ion trap, possessing predominantly octapole fields, was developed. This octapole ion trap exhibited higher trapping capacity than a quadrupole ion trap of similar geometry. However, mass analysis in the octapole ion trap was not achievable because ions were resonantly ejected over a broad frequency range. A second generation octapole ion trap, with improved resonance ejection characteristics, also was developed. Resonance ejection experiments in this geometry were in agreement with ion trajectory simulations, but mass analysis using resonance ejection was again not possible due to broad band ejection. A non-destructive Fourier transform detection method was simulated and found to be viable

An Interesting Case of Recurrent Small Bowel Obstruction

Sclerosing mesenteritis is associated with a spectrum of diseases which include mesenteric lipodystrophy and mesenteric panniculitis. This inflammatory and fibrosing disorder can affect the small and large bowel wall and mesenteric vessels by exerting a mass effect. The following case highlights the difficulties with diagnosing and managing this unusual disease. A 64-year-old man presented with acute central abdominal pain, radiating to his back, and profuse vomiting. He was diagnosed clinically with small bowel obstruction. He had had an episode of small bowel obstruction 6 years earlier. At this time, he underwent an exploratory laparotomy, and a mass was identified in the small bowel mesentery. The features were thought to be in keeping with sclerosing mesenteritis. He had a dramatically favourable response to the initiation of prednisolone. He continued to be well and asymptomatic for a further 5 years on long-term maintenance low-dose steroids and 6-mercaptopurine. He re-presented in 2009 (six years after initial presentation) with very severe acute abdominal pain and vomiting. He had no recent change in weight or appetite, and had not had time off work. He underwent a second laparotomy and the tissue diagnosis was of metastatic carcinoid tumour involving the small bowel mesentery. This is the first case to our knowledge where sclerosing mesenteritis has been confirmed histologically on biopsy and then subsequently diagnosed with histologically proven carcinoid tumour. For this particular reason it must be always remembered that sclerosing mesenteritis is a ‘pathological’ and not a radiological diagnosis and that a large proportion of cases are associated with neoplasia

Resource availability and barriers to delivering quality care for newborns in hospitals in the southern region of Malawi: A multisite observational study

Facility-based births have increased in low and middle-income countries, but babies still die due to poor care. Improving care leads to better newborn outcomes. However, data are lacking on how well facilities are prepared to support. We assessed the availability of human and material resources and barriers to delivering quality care for newborns and barriers to delivering quality care for newborns. We adapted the WHO Service Availability and Readiness Assessment tool to evaluate the resources for delivery and newborn care and barriers to delivering care, in a survey of seven hospitals in southern Malawi between January and February 2020. Data entered into a Microsoft Access database was exported to IBM SPSS 26 and Microsoft Excel for analysis. All hospitals had nursery wards with at least one staff available 24 hours, a clinical officer trained in paediatrics, at least one ambulance, intravenous cannulae, foetal scopes, weighing scales, aminophylline tablets and some basic laboratory tests. However, resources lacking some or all of the time included anticonvulsants, antibiotics, vitamin K, 50% dextrose, oxytocin, basic supplies such as cord clamps and nasal gastric tubes, laboratory tests such as bilirubin and blood culture and newborn clinical management guidelines. Staff reported that the main barriers to providing high-quality care were erratic supplies of power and water, inadequacies in the number of beds/cots, ambulances, drugs and supplies, essential laboratory tests, absence of newborn clinical protocols, and inadequate staff, including paediatric specialists, in-service training, and support from the management team. In hospitals in Malawi, quality care for deliveries and newborns was compromised by inadequacies in many human and material resources. Addressing these deficiencies would be expected to lead to better newborn outcomes

Quality of stillbirth and neonatal death audit in Malawi: A descriptive observational study

WHO developed a guideline for implementing stillbirth and neonatal death audits at healthcare facilities in 2016. Like many other poor resource countries, stillbirths and neonatal deaths rates remain high in Malawi despite implementation of audit. This paper assesses the quality of facility-based stillbirth and neonatal death audit implementation in Malawian hospitals and provides recommendations for improvement. In accordance with the WHO audit guidelines, we applied mixed methods to determine the quality of audit implementation in seven hospitals in Malawi. We reviewed hospital surveillance data; audit document forms and action plans. We sought staff perceptions and opinions through a questionnaire and interviews and observed audit meetings. Quantitative data was analysed using IBM SPSS 26.0 and presented using frequencies and proportions. Qualitative data were analysed using predefined themes in a survey guide. The frequency of audits and number of stillbirth and neonatal deaths audited varied significantly between hospitals. No hospital had national audit guidelines. Deficiencies included limited information on neonatal death audit data collection and reporting tools, incomplete documentation, lack of senior staff commitment and a blame or shame atmosphere. Audit meetings often did not start with review of ward statistics, previous minutes and follow-up as to whether previous recommendations had been implemented. Challenges in analysing audit information and recommending solutions resulted in lowquality action plans. No objective evidence was found that audit recommendations were implemented. Assessed according to WHO guidelines, audits were of low quality resulting in challenges in identifying and addressing factors contributing to mortality. We recommend regular audit implementation, with completion of audit cycles for audit to contribute to mortality reduction

Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst.

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is "vigilant" and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst

Factors impacting—stillbirth and neonatal death audit in Malawi: a qualitative study

Background: Over one million babies are stillborn or die within the first 28 days of life each year due to preventable causes and poor-quality care in resource-constrained countries. Death audit may be a valuable tool for improving quality of care and decreasing mortality. However, challenges in implementing audit and their subsequent action plans have been reported, with few successfully implemented and sustained. This study aimed to identify factors that affect stillbirth and neonatal death audit at the facility level in the southern region of Malawi. Methods: Thirty-eight semi-structured interviews and seven focus group discussions with death audit committee members were conducted. Thematic analysis was guided by a conceptual framework applied deductively, combined with inductive line-by-line coding to identify additional emerging themes. Results: The factors that affected audit at individual, facility and national level were related to training, staff motivation, power dynamics and autonomy, audit organisation and data support. We found that factors were linked because they informed each other. Inadequate staff training was caused by a lack of financial allocation at the facility level and donor-driven approaches to training at the national level, with training taking place only with support from funders. Staff motivation was affected by the institutional norms of reliance on monetary incentives during meetings, gazetted at the national level so that audits happened only if such incentives were available. This overshadowed other benefits and non-monetary incentives which were not promoted at the facility level. Inadequate resources to support audit were informed by limited facility-level autonomy and decision-making powers which remained controlled at the national level despite decentralisation. Action plan implementation challenges after audit meetings resulted from inadequate support at the facility level and inadequate audit policy and guidelines at the national level. Poor documentation affected audit processes informed by inadequate supervision and promotion of data usage at both facility and national levels. Conclusions: Given that the factors that facilitate or inhibit audits are interconnected, implementers, policymakers and managers need to be aware that addressing barriers is likely to require a whole health systems approach targeting all system levels. This will require behavioural and complex intervention approaches

Validation of a stochastic digital packing algorithm for porosity prediction in fluvial gravel deposits

Porosity as one of the key properties of sediment mixtures is poorly understood. Most of the existing porosity predictors based upon grain size characteristics have been unable to produce satisfying results for fluvial sediment porosity, due to the lack of consideration of other porosity-controlling factors like grain shape and depositional condition. Considering this, a stochastic digital packing algorithm was applied in this work, which provides an innovative way to pack particles of arbitrary shapes and sizes based on digitization of both particles and packing space. The purpose was to test the applicability of this packing algorithm in predicting fluvial sediment porosity by comparing its predictions with outcomes obtained from laboratory measurements. Laboratory samples examined were two natural fluvial sediments from the Rhine River and Kall River (Germany), and commercial glass beads (spheres). All samples were artificially combined into seven grain size distributions: four unimodal distributions and three bimodal distributions. Our study demonstrates that apart from grain size, grain shape also has a clear impact on porosity. The stochastic digital packing algorithm successfully reproduced the measured variations in porosity for the three different particle sources. However, the packing algorithm systematically overpredicted the porosity measured in random dense packing conditions, mainly because the random motion of particles during settling introduced unwanted kinematic sorting and shape effects. The results suggest that the packing algorithm produces loose packing structures, and is useful for trend analysis of packing porosity

Frequency and Clinical Determinants of Dementia after Ischemic Stroke

Objective: To investigate the frequency and clinical determinants of dementia after ischemic stroke. Methods: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 ± 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Results: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). Conclusions: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors’ cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke

An Equity-focused Assessment of the City of Richmond’s RVAgreen 2050 Planning Process

Local climate action and sustainability initiatives are often critiqued for their inattention to issues of equity and justice. In response, an increasing number of cities are now attempting to respond to this critique by making equity a more explicit goal of their climate action plans: Richmond Virginia is among those cities. The City of Richmond\u27s Office of Sustainability committed to prioritizing equity in the RVAGreen 2050 plan by recognizing how Richmond’s history of racism and structural inequalities have exacerbated climate concerns for largely Black and Latinx communities and centering historically marginalized communities of color in the engagement process. Students in URSP 637 Sustainable Community Development were asked to provide an external evaluation of the RVAGreen 2050 planning process. This report summarizes the findings of this evaluation and highlights recommendations for how to improve equity-centered engagement processed moving forward