D.I.Y. Clean Hood

The DIY Clean Hood is a low-cost, sterile, and accessible scientific workspace intended for installation in the BioElectroFluidics Lab of California Polytechnic State University’s (San Luis Obispo) Biomedical Engineering Department (BMED), under the sponsorship of Dr. Benjamin Hawkins, PhD. As normal Clean Hood, Biosafety Cabinets, and the like are generally too expensive for a university, a competitive solution to an expensive problem can assist research students and professors alike continue their own work with an inexpensive yet effective environment. Specific design elements that the customer requirements entailed for the project include a low-particle-count air filtration system, positive pressure air flow inside the vessel, and compatibility with common cleaning agents. These critical details for the DIY Clean Hood are to ensure that the cell cultures being cultivated and studied are free from any foreign contaminants or agents that could compromise the product. Unlike the original, mislabeled identification of the project as a “DIY Biosafety Cabinet”, it is not the responsibility of the Clean Hood to protect either the environment or the user of the DIY Clean Hood. Despite the non-hazardous conditions of the cells being manipulated, proper design components and features ensure sterility and effectiveness. Other notable design elements of the DIY Clean Hood include a 15 degree angled, swinging sash opening, an air filtration system utilizing a HEPA (High-Efficiency Particulate Air) filter, an installed UV light for an additional sterilization option, and a wide opening for comfortable mobility while using the Clean Hood. The project was a recipient of the Biomedical Engineering Department’s Hannah-Forbes Grant, which allows the DIY Clean Hood project an additional $500 towards any necessary purchases and bringing the total budget to$700. Due to the onset of the COVID-19 pandemic, the project required its focus to shift from a manufacturing and qualification testing standpoint to a more design and technically-centered frame, as several factors prevented the project from proceeding originally as planned. These included, but were not limited to, the closure of manufacturing and assembly facilities on the Cal Poly campus, anticipated delays in material acquisition due to non-essential items, social distancing of team members, and limited alternative build options. This decision was agreed upon in correspondence with project sponsor Dr. Hawkins, Engineering Design overseer Dr. Michael Whitt, and the members of the DIY Clean Hood Team. As a result, the DIY Clean Hood prepared a final, detailed design for the product to ensure all customer requirements were met in approaches the team thought would provide the best performance and usability; the BioElectroFluidics lab will find a team of their own in late 2020 to build the device using the enclosed detailed designs, and qualify the product with the DIY Clean Hood’s testing protocols

Ineffectiveness in Teacher Bargaining: The Anatomy of a First Strike

Dans l'étude et la pratique de la négociation collective, on se heurte toujours à la possibilité d'une grève qui peut être potentiellement néfaste. Lorsque, de plus, les parties sont des novices dans l'art de négocier et qu'elles font face à un état de grève pour la première fois, il est probable qu'elles auront un comportement qui laisse à désirer et qui peut conduire à des résultats désastreux.Cette étude traite spécifiquement d'une « première grève » et propose une série de faits qui caractérisent de pareilles situations. Ces facteurs sont ensuite utilisés dans l'analyse des événements qui entourent une grève dans le secteur de l'enseignement où les deux parties, le syndicat et la commission scolaire, en étaient à leur première expérience.Lorsqu'il s'agit d'une première grève, on peut s'attendre à ce que, comparés à des négociateurs plus expérimentés, les responsables de la négociation soient (1) moins bien informés et plus hésitants, ce qui conduit à une perception moins nette des événements et à un comportement irrationnel; (2) qu'ils se montrent méfiants à l'endroit des autres parties; (3) qu'ils s'appuient sur des raisons émotives; (4) qu'ils adoptent une attitude défensive et agressive; (5) qu'ils optent pour des modes de communication inadéquats; (6) qu'ils aient recours à des aides professionnels moins compétents, ce qui a pour effet d'accroître les autres difficultés.L'examen de ce qui s'est passé au cours de cette grève d'enseignants a révélé que, d'une façon générale, le syndicat a subi des préjudices graves et inutiles comme résultat de sa décision de faire la grève, en obtenant qu'un petit peu plus que ce que lui avait offert la commission scolaire immédiatement avant la grève. Des communications réticentes et sélectives, alors que l'une et l'autre parties jouaient à cache-cache, le manque de conseils à la section locale de la part du siège social du syndicat, la négligence des dirigeants syndicaux à renseigner les membres sur des faits importants qui se rapportaient directement au conflit comme les offres salariales, des erreurs dans la stratégie de négociation qui ont placé le syndicat dans une situation désavantageuse, des attitudes de plus en plus émotives et agressives entre les parties au fur et à mesure que les négociations se poursuivaient, autant de faits qui ont caractérisé ces négociations. Le syndicat laissa passer la période la plus propice à la grève au commencement de l'automne au moment de l'ouverture des classes alors que la commission scolaire était moins prête à affronter la grève.La grève elle-même fut assez violente; elle a laissé de profonds ressentiments et une méfiance prolongée entre les parties. Les dirigeants syndicaux ont été emprisonnés une semaine pendant la grève. Les cours furent perturbés et les policiers furent forcés de maîtriser les grévistes. Les membres en général furent surpris par la dureté de la grève et par la fermeté de la commission scolaire à maintenir sa position. Le président de la commission scolaire remet peu après sa démission à cause d'animosité et de pressions sous forme d'appels téléphoniques outranciers, de lettres haineuses et d'altercation publique avec les membres du syndicat.Les événements et les expériences qui ont marqué cette grève diffèrent de la plupart des grèves d'enseignants qui ont été analysées jusqu'ici, ce qui indique que les premières grèves méritent une étude spéciale en tant que forme originale de conflits qui possèdent leurs caractéristiques et leurs dynamisme propres.On peut donc conclure que les parties à une première grève devraient se rendre compte de la probabilité plus forte des dangers dont il vient d'être question et qu'elles devraient mieux se préparer aux réalités de la négociation collective, se doter d'une aide professionnelle compétente, être prêtes à faire des compromis et être conscientes des effets prolongés de comportements néfastes pour les négociations futures.The objective of this paper is to identify characteristics which distinguish first strike situations from other strike actions. It is based on both collective bargaining and conflict resolution literature as well as the detailed analysis of a recent walkout by a public school teachers' union

Denying renal transplantation to an adolescent medical cannabis user: An ethical case study

Medical cannabis is now legal in over half of the United States. As more patients adopt this unconventional therapy, it is inevitable that potential transplant recipients will disclose their cannabis use during transplant evaluation. Transplant teams are tasked with the decision to utilize a pressure resource, often with little guidance from international and national professional organizations. Many healthcare providers remain uniformed or misinformed about the risks of cannabis use and organ transplantation. In order to illustrate the multifaceted and complex evaluation of transplant patients using medical cannabis, this article presents the case of a 20‐year‐old woman recommended for renal transplant who was originally denied active listing due to her medical cannabis use. A review of the literature explores the perceived and actual risks of cannabis use in the immunocompromised patient. Furthermore, a discussion of the ethics of medical cannabis use and organ transplantation is included with recommendations for multidisciplinary transplant teams.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150568/1/petr13467.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150568/2/petr13467_am.pd

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell

Ceruloplasmin Plays a Neuroprotective Role in Cerebral Ischemia

Ceruloplasmin (Cp) is a ferroxidase that also plays a role in iron efflux from cells. It can thus help to regulate cellular iron homeostasis. In the CNS, Cp is expressed as a membrane-anchored form by astrocytes. Here, we assessed the role of Cp in permanent middle cerebral artery occlusion (pMCAO) comparing wildtype and Cp null mice. Our studies show that the lesion size is larger and functional recovery impaired in Cp null mice compared to wildtype mice. Expression of Cp increased ninefold at 72 h after pMCAO and remained elevated about twofold at day 14. We also assessed changes in mRNA and protein expression of molecules involved in iron homeostasis. As expected there was a reduction in ferroportin in Cp null mice at 72 h. There was also a remarkable increase in DMT1 protein in both genotypes at 72 h, being much higher in wildtype mice (19.5-fold), that then remained elevated about twofold at 14 days. No difference was seen in transferrin receptor 1 (TfR1) expression, except a small reduction in wildtype mice at 72 h, suggesting that the increase in DMT1 may underlie iron uptake independent of TfR1-endosomal uptake. There was also an increase of ferritin light chain in both genotypes. Iron histochemistry showed increased iron accumulation after pMCAO, initially along the lesion border and later throughout the lesion. Immunofluorescence labeling for ferritin (a surrogate marker for iron) and GFAP or CD11b showed increased ferritin in GFAP+ astrocytes along the lesion border in Cp null mice, while CD11b+ macrophages expressed ferritin equally in both genotypes. Increased lipid peroxidation assessed by 4HNE staining was increased threefold in Cp null mice at 72 h after pMCAO; and 3-nitrotyrosine labeling showed a similar trend. Three key pro-inflammatory cytokines (IL-1β, TNFα, and IL-6) were markedly increased at 24 h after pMCAO equally in both genotypes, and remained elevated at lower levels later, indicating that the lack of Cp does not alter key inflammatory cytokine expression after pMCAO. These data indicate that Cp expression is rapidly upregulated after pMCAO, and loss of Cp results in dysregulation of iron homeostasis, increased oxidative damage, greater lesion size and impaired recovery of function

Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance.

BACKGROUND: Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert® MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens. OBJECTIVES: To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction. SELECTION CRITERIA: We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results. MAIN RESULTS: We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB. AUTHORS' CONCLUSIONS: In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative

Session availability as a result of prior injury impacts the risk of subsequent injury in elite male Australian footballers

Prior injury is a commonly identified risk factor for subsequent injury. However, a binary approach to classifying prior injury (i.e., yes/no) is commonly implemented and may constrain scientific findings, as it is possible that variations in the amount of time lost due to an injury will impact subsequent injury risk to differing degrees. Accordingly, this study investigated whether session availability, a surrogate marker of prior injury, influenced the risk of subsequent non-contact lower limb injury in Australian footballers. Data were collected from 62 male elite Australian footballers throughout the 2015, 2016, and 2017 Australian Football League seasons. Each athlete’s participation status (i.e., full or missed/modified) and any injuries that occurred during training sessions/matches were recorded. As the focus of the current study was prior injury, any training sessions/matches that were missed due to reasons other than an injury (e.g., load management, illness and personal reasons) were removed from the data prior to all analyses. For every Monday during the in-season periods, session availability (%) in the prior 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84 days was determined as the number of training sessions/matches fully completed (injury free) relative to the number of training sessions/matches possible in each window. Each variable was modeled using logistic regression to determine its impact on subsequent injury risk. Throughout the study period, 173 non-contact lower limb injuries that resulted in at least one missed/modified training session or match during the in-season periods occurred. Greater availability in the prior 7 days increased injury probabilities by up to 4.4%. The impact of session availability on subsequent injury risk diminished with expanding windows (i.e., availability in the prior 14 days through to the prior 84 days). Lesser availability in the prior 84 days increased injury probabilities by up to 14.1%, only when coupled with greater availability in the prior 7 days. Session availability may provide an informative marker of the impact of prior injury on subsequent injury risk and can be used by coaches and clinicians to guide the progression of training, particularly for athletes that are returning from long periods of injury

Circulating microRNA responses to acute whole-body vibration and resistance exercise in postmenopausal women

Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) (3 sets 10 reps 70% 1 repetition maximum (1RM), 5 exercises) and a bout of whole-body vibration (WBV) (5 sets 1 min bouts 20Hz 3.38mm peak to peak displacement, Vibraflex vibration platform). DXA was used to measure body composition and areal bone mineral density (aBMD) of the total body, AP lumbar spine, and dual proximal femur. pQCT was used to measure tibia bone characteristics (4%, 38%, 66% sites). Blood samples were collected before exercise (Pre), immediately-post (IP), 60 minutes post (60P), 24 hours (24H), and 48 hours (48H) after exercise to measure serum miR-21-5p, -23a-3p, -133a-3p, -148a-3p (qPCR) and TRAP5b (ELISA). There was a significant modality × time interaction for c-miR-21-5p expression (p=0.019), which decreased from 60P to 24H after WBV only. TRAP5b serum concentrations significantly increased IP then decreased below Pre at 24H for both WBV and RE (p\u3c0.01). Absolute changes in TRAP5b were negatively correlated with c-miR-21-5p fold changes (r= -0.642 to -0.724, p\u3c0.05) for both exercise modalities. There were significant negative correlations between baseline c-miRNAs and bone status variables (r= -0.639 to -0.877, p\u3c0.05). Our findings suggest that whole-body vibration is a sufficient mechanical stimulus for altering c-miR-21-5p expression, whereas a high intensity resistance exercise protocol did not elicit any c-miRNA responses in postmenopausal women. Increases in the bone resorption marker, TRAP5b, were associated with greater downregulation of c-miR-21-5p expression

Chern-Simons functional and the no-boundary proposal in Bianchi IX quantum cosmology

The Chern-Simons functional $S_{\rm CS}$ is an exact solution to the Ashtekar-Hamilton-Jacobi equation of general relativity with a nonzero cosmological constant. In this paper we consider $S_{\rm CS}$ in Bianchi type IX cosmology with $S^3$ spatial surfaces. We show that among the classical solutions generated by~$S_{\rm CS}$, there is a two-parameter family of Euclidean spacetimes that have a regular NUT-type closing. When two of the three scale factors are equal, these spacetimes reduce to a one-parameter family within the Euclidean Taub-NUT-de~Sitter metrics. For a nonzero cosmological constant, $\exp(iS_{\rm CS})$ therefore provides a semiclassical estimate to the Bianchi~IX no-boundary wave function in Ashtekar's variables.Comment: 9 pages, REVTeX v3.0. (One reference added.