The Perfect Storm: Strategies for Weathering Change in Technical Services

This paper describes the approach to three simultaneous problems faced by technical services at the College of Charleston Libraries: the retirement of the department head, the outbreak of the COVID-19 pandemic, and the migration to a new library management system

A state of poverty: Critical realism of socio-economic problems in the works of Charles Dickens

Oppgaven tar for seg de sosiale problemene på tiden der Oliver Twist ble skrevet, og hvordan disse problemene fortsatt er relevant for dagens samfunn.This paper deals with the socio-economic problems of the time in which Oliver Twist was written, and it also looks at how these issues still are relevant in today's society

Amiodarone-induced bone marrow granulomas: an unusual cause of reversible pancytopenia

Bone marrow infiltration by granulomas rarely presents with cytopenias and is usually a result of atypical infections, lymphomas, or sarcoidosis. Drugs are also an important but often overlooked causal agent of bone marrow granulomas. Although rare, amiodarone has been associated with bone marrow granuloma formation. This case report describes a 73-year-old male who presented with pancytopenia during a preoperative evaluation. Amiodarone therapy was suspected to be the causal agent after diagnostic evaluation and exclusion of other causes. After cessation of amiodarone, the patient's pancytopenia gradually resolved over a period of several months. Our report illustrates an often overlooked yet important cause of reversible pancytopenia owing to suspected amiodarone-induced bone marrow granuloma formation, and guides clinicians in an expected timeline for blood count improvement after cessation of this drug

Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2%) study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4%) control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%). Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

Symptom Burden in Long-Term Survivors of Head and Neck Cancer: Patient-Reported Versus Clinical Data

Introduction: The symptom burden faced by long-term head and neck cancer survivors is not well understood. In addition, the accuracy of clinical data sources for symptom ascertainment is not clear. Objective: To 1) describe the prevalence of symptoms in 5-year survivors of head and neck cancer, and 2) to evaluate agreement between symptoms obtained via self-report and symptoms obtained from clinical data sources. Methods: We recruited 5-year survivors of head and neck cancer enrolled at Kaiser Permanente Washington (n = 54). Symptoms were assessed using the MD Anderson Symptom Inventory head and neck cancer module. For each symptom, we assessed the agreement of the patient\u27s survey response ( gold standard ) with the 1) medical chart and 2) administrative health care claims data. We computed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value, along with their 95 percent confidence intervals, for each clinical data source. Results: Eighty percent of patients responded. Nearly all participants (95 percent) reported experiencing at least one symptom from the MDASI-HN, and 93 percent reported two or more symptoms. Among patients reporting a given symptom, there was generally no evidence of the symptom from either clinical data source (i.e., sensitivity was generally no greater than 40 percent). The specificity and PPV of the clinical data sources were generally higher than the sensitivity. Conclusion: Relying only on medical chart review and/or administrative health data would substantially underestimate symptom burden in long-term head and neck cancer survivors

Quantifying ecological variation across jurisdictional boundaries in a management mosaic landscape

Context Large landscapes exhibit natural heterogeneity. Land management can impose additional variation, altering ecosystem patterns. Habitat characteristics may reflect these management factors, potentially resulting in habitat differences that manifest along jurisdictional boundaries. Objectives We characterized the patchwork of habitats across a case study landscape, the Grand Canyon Protected Area-Centered Ecosystem. We asked: how do ecological conditions vary across different types of jurisdictional boundaries on public lands? We hypothesized that differences in fire and grazing, because they respond to differences in management over time, contribute to ecological differences by jurisdiction. Methods We collected plot-scale vegetation and soils data along boundaries between public lands units surrounding the Grand Canyon. We compared locations across boundaries of units managed differently, accounting for vegetation type and elevation differences that pre-date management unit designations. We used generalized mixed effects models to evaluate differences in disturbance and ecology across boundaries. Results Jurisdictions varied in evidence of grazing and fire. After accounting for these differences, some measured vegetation and soil properties also differed among jurisdictions. The greatest differences were between US Forest Service wilderness and Bureau of Land Management units. For most measured variables, US Forest Service non-wilderness units and National Park Service units were intermediate. Conclusions In this study, several ecological properties tracked jurisdictional boundaries, forming a predictable patchwork of habitats. These patterns likely reflect site differences that pre-date jurisdictions as well as those resulting from different management histories. Understanding how ecosystem differences manifest at jurisdictional boundaries can inform resource management, conservation, and cross-boundary collaborations

Multisite verification of the accuracy of a multi-gene next generation sequencing panel for detection of mutations and copy number alterations in solid tumours

Molecular variants including single nucleotide variants (SNVs), copy number variants (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection using little genomic input material. They are gaining in popularity in clinical laboratories, where sample volumes are limited, and low variant allele fractions may be present. However, data on reproducibility between laboratories is limited. Using a ring study, we evaluated the performance of 7 Ontario laboratories using targeted sequencing panels. All laboratories analysed a series of control and clinical samples for SNVs/CNVs and gene fusions. High concordance was observed across laboratories for measured CNVs and SNVs. Over 97% of SNV calls in clinical samples were detected by all laboratories. Whilst only a single CNV was detected in the clinical samples tested, all laboratories were able to reproducibly report both the variant and copy number. Concordance for information derived from RNA was lower than observed for DNA, due largely to decreased quality metrics associated with the RNA components of the assay, suggesting that the RNA portions of comprehensive NGS assays may be more vulnerable to variations in approach and workflow. Overall the results of this study support the use of the OFA for targeted sequencing for testing of clinical samples and suggest specific internal quality metrics that can be reliable indicators of assay failure. While we believe this evidence can be interpreted to support deep targeted sequencing in general, additional studies should be performed to confirm this

Multisite verification of the accuracy of a multi-gene next generation sequencing panel for detection of mutations and copy number alterations in solid tumours

Molecular variants including single nucleotide variants (SNVs), copy number variants (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection using little genomic input material. They are gaining in popularity in clinical laboratories, where sample volumes are limited, and low variant allele fractions may be present. However, data on reproducibility between laboratories is limited. Using a ring study, we evaluated the performance of 7 Ontario laboratories using targeted sequencing panels. All laboratories analysed a series of control and clinical samples for SNVs/CNVs and gene fusions. High concordance was observed across laboratories for measured CNVs and SNVs. Over 97% of SNV calls in clinical samples were detected by all laboratories. Whilst only a single CNV was detected in the clinical samples tested, all laboratories were able to reproducibly report both the variant and copy number. Concordance for information derived from RNA was lower than observed for DNA, due largely to decreased quality metrics associated with the RNA components of the assay, suggesting that the RNA portions of comprehensive NGS assays may be more vulnerable to variations in approach and workflow. Overall the results of this study support the use of the OFA for targeted sequencing for testing of clinical samples and suggest specific internal quality metrics that can be reliable indicators of assay failure. While we believe this evidence can be interpreted to support deep targeted sequencing in general, additional studies should be performed to confirm this

Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level