Cyberbiosecurity in high-containment laboratories.

High-containment laboratories (HCLs) conduct critical research on infectious diseases, provide diagnostic services, and produce vaccines for the world's most dangerous pathogens, often called high-consequence pathogens (HCPs). The modernization of HCLs has led to an increasingly cyber-connected laboratory infrastructure. The unique cyberphysical elements of these laboratories and the critical data they generate pose cybersecurity concerns specific to these laboratories. Cyberbiosecurity, the discipline devoted to the study of cybersecurity risks in conjunction with biological risks, is a relatively new field for which few approaches have been developed to identify, assess, and mitigate cyber risks in biological research and diagnostic environments. This study provides a novel approach for cybersecurity risk assessment and identification of risk mitigation measures by applying an asset-impact analysis to the unique environment of HCLs. First, we identified the common cyber and cyberphysical systems in HCLs, summarizing the typical cyber-workflow. We then analyzed the potential adverse outcomes arising from a compromise of these cyber and cyberphysical systems, broadly categorizing potential consequences as relevant to scientific advancement, public health, worker safety, security, and the financial wellbeing of these laboratories. Finally, we discussed potential risk mitigation strategies, leaning heavily on the cybersecurity materials produced by the Center for Internet Security (CIS), including the CIS Controls®, that can serve as a guide for HCL operators to begin the process of implementing risk mitigation measures to reduce their cyberbiorisk and considering the integration of cyber risk management into existing biorisk management practices. This paper provides a discussion to raise awareness among laboratory decision-makers of these critical risks to safety and security within HCLs. Furthermore, this paper can serve as a guide for evaluating cyberbiorisks specific to a laboratory by identifying cyber-connected assets and the impacts associated with a compromise of those assets.

Using a rapid ethnographic assessment to explore vaccine hesitancy on a public university campus in the Upper Midwest.

Objective: This exploratory study examined campus attitudes toward vaccines to guide subsequent development of context-relevant interventions for increasing vaccine acceptance and uptake. Participants: We gathered ethnographic data on a convenience sample of campus community members (students, faculty, staff) at a public university over six weeks in spring 2022. Methods: Student researchers conducted a rapid ethnographic assessment across campus locations. Weekly team debriefs enabled ongoing, iterative refinement of instruments and supplemented observational fieldnotes. Data analysis was inductive and oriented toward practical recommendations for intervention development. Results: Four themes, and attendant recommendations, emerged: 1) social identities and social roles influence health-related beliefs, including vaccination; 2) vaccine knowledge influences vaccination behaviors; 3) language surrounding vaccines (sometimes) matters; 4) vaccines aren't considered part of general health and wellness and can't be forced. Conclusions: Findings highlight the need to address individual, social, and institutional contexts when designing campus-based behavioral interventions for vaccine uptake.

Multidisciplinary management of missing maxillary central incisors in children and adolescents.

Missing maxillary central incisors can impact a patient's psychological wellbeing and smile aesthetics. Comprehensive management of such cases requires a multidisciplinary team approach, often involving orthodontic, paediatric and restorative dental teams. This paper summarises the various management options for these complex patients.

Visual inspection with acetic acid screening for cervical cancer among women receiving anti-retroviral therapy for human immunodeficiency virus infection in northern Tanzania.

AIM: To evaluate visual inspection with acetic acid (VIA) screening for cervical cancer among human immunodeficiency virus (HIV)-positive patients in an East African community. METHODS: During a July 2018 cervical cancer screen-and-treat in Mwanza, Tanzania, participants were offered free cervical VIA screening, cryotherapy when indicated, and HIV testing. Acetowhite lesions and/or abnormal vascularity were designated VIA positive in accordance with current guidelines. The association between VIA results and HIV status was compared using Chi-square and Fisher exact tests. RESULTS: Eight hundred and twenty-four of 921 consented participants underwent VIA screening and 25.0% (n = 206) were VIA positive. VIA-positive nonpregnant women (n = 147) received cryotherapy and 15 (1.8%) with cancerous-appearing lesions were referred to Bugando Hospital. Sixty-six women were HIV-positive and included 25 diagnosed with HIV at the cervical cancer VIA screening and 41 with a prior diagnosis of HIV who were receiving antiretroviral therapy (ART) at the time of cervical cancer VIA screening. Sixty-four of these 66 patients, were screened with VIA. HIV infection was not associated with VIA findings. Abnormal VIA positive screening was observed in 20.3% (n = 13) of HIV-positive patients and in 24.4% (n = 145) of HIV-negative patients (p = 0.508). A nonsignificant trend of higher VIA positive screens among newly diagnosed HIV patients of 26.1% (n = 6) versus patients with preexisting HIV on ART of 17.1% (n = 7) was observed (p = 0.580). CONCLUSION: The unexpected lack of correlation between HIV infection and VIA positivity in a community with access to ART warrants additional research regarding the previously described role of ART in attenuating HPV-mediated neoplasia.

Implementation of human papillomavirus video education for women participating in mass cervical cancer screening in Tanzania.

BACKGROUND: Because the global disease burden of cervical cancer is greatest in Africa, the World Health Organization has endorsed visual inspection with acetic acid screening with cryotherapy triage for the screen-and-treat approach. With the lowest doctor-to-patient ratio worldwide (1:50,000), Tanzania has nearly 10,000 new cases of cervical cancer and 7000 deaths annually. OBJECTIVE: We report on the feasibility of visual inspection with acetic acid in the severely resource-limited Mwanza district and on the impact of intervening education on baseline human papillomavirus and cervical cancer knowledge. STUDY DESIGN: Two 5-day free visual inspection with acetic acid (VIA) clinics in urban Buzuruga and rural Sangabuye on the shores of Lake Victoria were approved by our university institutional review board and local Tanzanian health authorities. Participants completed a demographic survey and a 6-question (1 point per question) multiple choice test written in Kiswahili to assess baseline knowledge. A 15-minute educational video in Kiswahili (MedicalAidFilms: Understanding screening, treatment, and prevention of cervical cancer) was followed by repeated assessment using the same test, visual inspection with acetic acid screening, and optional HIV testing. Pre- and postvideo scores and change of score were analyzed via t test, analysis of variance, and multivariate regression. Significance was considered at P<.05. RESULTS: From July 2, 2018 to July 6, 2018, 825 women were screened, and 207 women (25.1%) were VIA positive (VIA+). One hundred forty-seven VIA+ nonpregnant women received same-day cryotherapy. Seven hundred sixty women participated in an educational intervention-61.6% of whom were from an urban site and 38.2% from a rural site. The mean age was 36.4 (standard deviation, 11.1). Primary languages were Kiswahili (62.2%) and Kisukuma (30.6%). Literacy was approximately 73%, and average education level was equivalent to the seventh grade (United States). Less than 20% of urban and rural women reported access to healthcare providers. Mean score of the participants before watching the video was 2.22 (standard deviation, 1.76) and was not different between VIA+ and VIA negative groups. Mean score of the participants after watching the video was 3.86 (standard deviation, 1.78). Postvideo scores significantly improved regardless of age group, clinic site, primary language, education level, literacy, or access to healthcare provider (P<.0001). Change of score after watching the video was significantly greater in participants from urban areas (1.99±2.07) than in those from rural areas (1.07±1.95) (P<.0001). Multivariate analysis identified urban site as an independent factor in change of score (P=.0211). CONCLUSION: Visual inspection with acetic acid screening for cervical cancer is feasible and accepted in northern Tanzania. Short video-based educational intervention improved baseline knowledge on the consequences of human papillomavirus infection in the studied populations. The impact was greater in the urban setting than in the rural setting.

The effective use of an e-dentistry service during the COVID-19 crisis.

In 2020, we experienced the largest disruption to normal life recorded in recent years with the COVID-19 global pandemic. Creative thinking was required to ensure patient care was maintained. In this article, we share a service evaluation and experiences dealing with the crisis through using a virtual office approach with video conferencing to manage emergency consultations, treatment reviews, new patient and multidisciplinary clinics in a hospital orthodontic unit.

Identifying Information Needs for Hirschsprung Disease Through Caregiver Involvement via Social Media: A Prioritization Study and Literature Review.

BACKGROUND: Patient and public involvement in health research is important to produce relevant and impactful results. OBJECTIVE: This paper aimed to prioritize and summarize Hirschsprung disease (HD)-related information needs among caregivers of children with HD and pediatric surgeons through partnership with a parent-initiated social media campaign. METHODS: We conducted a Web-based survey with the 2 stakeholder groups to identify information needs. The caregiver survey was conducted through a global Web-based community, and the surgeon survey was distributed to members of the Canadian Association of Paediatric Surgeons (CAPS). We conducted a literature review to identify evidence on the prioritized topics. RESULTS: Our findings showed that 54.9% (89/162) of the individuals completed the caregiver survey and 23.8% (52/218 listed members) of the pediatric surgeons completed the survey distributed through CAPS. Only 20% (18/89) of the caregivers reported being very satisfied or satisfied with the current HD-related resources. A final prioritized list of information needs included bowel management, nutrition and growth, infection, perianal irritation, gastrointestinal pain, surgical diagnostics, and surgical complications. In total, 87 studies were included in the literature review, which included the following: 8 reviews, 2 randomized controlled trials, 74 cohort studies, and 3 practice guidelines. Two priority issues identified by caregivers had only a single study that met the inclusion criteria, whereas 1 topic had none. CONCLUSIONS: With caregiver and surgeon input, we identified 7 information priority areas related to HD. A review of the literature on the priorities found little evidence to support the development of high-quality guidelines. More research is necessary to meet the information needs related to HD as identified by stakeholders.

Natural History of Postnatal Cardiopulmonary Adaptation in Infants Born Extremely Preterm and Risk for Death or Bronchopulmonary Dysplasia.

OBJECTIVE: To study the natural history of postnatal cardiopulmonary adaptation in infants born extremely preterm and establish its association with death or bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a prospective, observational, cohort study of infants born extremely preterm (<29 weeks). Initial echocardiogram was performed at <48 hours of life, followed by serial echocardiograms every 24-48 hours until 14 days of life. Resolution or no resolution of pulmonary hypertension (PH) at 72-96 hours was considered normal or delayed postnatal cardiopulmonary adaptation, respectively. PH between 96 hours and 14 days was defined as subsequent PH. Elevated pulmonary artery pressure throughout the 14 days of life was considered persistent PH. BPD was assessed at 36 weeks of postmenstrual age. RESULTS: Sixty infants were enrolled; 2 died before a sequential echocardiogram could be done at 72-96 hours. Normal and delayed cardiopulmonary adaptation were noted in 26 (45%) and 32 (55%) infants, respectively. Five patterns of postnatal cardiopulmonary adaptation were recognized: normal without subsequent PH (n = 20), normal with subsequent PH (n = 6), delayed adaptation without subsequent PH (n = 6), delayed adaptation with subsequent PH (n = 16), and persistent PH (n = 10). Infants with delayed cardiopulmonary adaptation were of lower gestation and birth weight and required prolonged ventilation and supplemental oxygen (P < .05). On multivariate analysis, the incidence of death or BPD was significantly greater among infants with delayed adaptation (P < .001). CONCLUSION: Infants born extremely preterm have normal or delayed postnatal cardiopulmonary adaptation that can be complicated by subsequent or persistent PH. Delayed cardiopulmonary adaptation is associated independently with death or BPD.

Rapid fingerprinting of lignin by ambient ionization high resolution mass spectrometry and simplified data mining.

Ambient ionization techniques are typically used to analyze samples in their native states with minimal or no sample pretreatment prior to mass spectrometric (MS) analysis. Desorption electrospray ionization (DESI) and direct analysis in real time (DART) were systematically investigated in this work for direct solid analysis of depolymerized lignin samples, with the goal of rapidly fingerprinting these samples, to efficiently characterize the subunits of this renewable energy source. High resolution MS was required for enhanced selectivity in this study due to the inherent structural complexity of lignin. DESI provided results across a broader mass range (up to m/z 700) than DART and also ionized saturated compounds of low oxygen-to-carbon (O/C) ratios and low double bond equivalents (DBE). While DART detected the same core lignin monomeric and dimeric compounds as seen with DESI and electrospray ionization (ESI), results were restricted to a narrower mass range to m/z 500, due to thermal degradation and losses of methoxy groups. In contrast to DESI and ESI, the DART spectra were nearly void of saturated components. On a structural level, the core lignin compounds were visually fingerprinted and ionization method performances critically assessed by employing simplified Kendrick-based data mining approaches. A novel simplified data visualization approach was developed in this work based on modified Kendrick mass defect (KMD) filtering for lignin subunits and plotting the mass defect values against the degree of unsaturation. Direct visualization of monomeric, dimeric and trimeric lignin species was simplified by the KMD separation plots, easily allowing the core lignin compounds to be visually identified and compared. Modified KMD bases, namely methoxy and phenol bases, which represent monomer-specific lignin constituents, were successfully used to classify and group the complex mixture of lignin species. Further separation of methoxy-related lignin species was successfully achieved by employing the more specific phenolic KMD base.

The Efficacy of Case Management on Emergency Department Frequent Users: An Eight-Year Observational Study.

BACKGROUND: Case management is an effective short-term means to reduce Emergency Department (ED) visits in frequent users of the ED. OBJECTIVES: Our study aimed to assess the long-term efficacy of intensive case management in frequent users of the ED. METHODS: This was an observational study of ED usage conducted at a community hospital that has an ED case management program in which frequent users of the ED are enrolled and provided with intensive care management to reduce ED use. RESULTS: We identified 199 patients that were enrolled for 6 or more years. Patients averaged 16 visits per person per year in the year prior to enrollment. Patients averaged the following number of visits per person per year after enrollment: year 1 (7.1), year 2 (4.1), year 3 (3.1), year 4 (3.3), year 5 (3.1), year 6 (2.0), year 7 (2.1), and year 8 (1.9), all statistically significant compared to the year prior to enrollment. Twenty-nine patients, despite case management, continued their frequent use, and required a revision to their plan of care. Five patients required a second revision to their plan of care secondary to recurrent ED usage. Persistent use despite case management was primarily due to prescription medication misuse and chronic pain. CONCLUSION: Case management of ED frequent users seems to be an effective means to reduce ED usage in both the short and long term. Patients with prescription drug misuse or chronic pain may continue to demonstrate frequent use despite case management, and may require revisions to their plan of care.

Real Time Monitoring of Containerless Microreactions in Acoustically Levitated Droplets via Ambient Ionization Mass Spectrometry.

Direct in-droplet (in stillo) microreaction monitoring using acoustically levitated micro droplets has been achieved by combining acoustic (ultrasonic) levitation for the first time with real time ambient tandem mass spectrometry (MS/MS). The acoustic levitation and inherent mixing of microliter volumes of reactants (3 µL droplets), yielding total reaction volumes of 6 µL, supported monitoring the acid-catalyzed degradation reaction of erythromycin A. This reaction was chosen to demonstrate the proof-of-principle of directly monitoring in stillo microreactions via hyphenated acoustic levitation and ambient ionization mass spectrometry. The microreactions took place completely in stillo over 30, 60, and 120 s within the containerless stable central pressure node of an acoustic levitator, thus readily promoting reaction miniaturization. For the evaluation of the miniaturized in stillo reactions, the degradation reactions were also carried out in vials (in vitro) with a total reaction volume of 400 µL. The reacted in vitro mixtures (6 µL total) were similarly introduced into the acoustic levitator prior to ambient ionization MS/MS analysis. The in stillo miniaturized reactions provided immediate real-time snap-shots of the degradation process for more accurate reaction monitoring and used a fraction of the reactants, while the larger scale in vitro reactions only yielded general reaction information.

A routine quality assurance test for CT automatic exposure control systems.

The study purpose was to develop and validate a quality assurance test for CT automatic exposure control (AEC) systems based on a set of nested polymethylmethacrylate CTDI phantoms. The test phantom was created by offsetting the 16 cm head phantom within the 32 cm body annulus, thus creating a three part phantom. This was scanned at all acceptance, routine, and some nonroutine quality assurance visits over a period of 45 months, resulting in 115 separate AEC tests on scanners from four manufacturers. For each scan the longitudinal mA modulation pattern was generated and measurements of image noise were made in two annular regions of interest. The scanner displayed CTDIvol and DLP were also recorded. The impact of a range of AEC configurations on dose and image quality were assessed at acceptance testing. For systems that were tested more than once, the percentage of CTDIvol values exceeding 5%, 10%, and 15% deviation from baseline was 23.4%, 12.6%, and 8.1% respectively. Similarly, for the image noise data, deviations greater than 2%, 5%, and 10% from baseline were 26.5%, 5.9%, and 2%, respectively. The majority of CTDIvol and noise deviations greater than 15% and 5%, respectively, could be explained by incorrect phantom setup or protocol selection. Barring these results, CTDIvol deviations of greater than 15% from baseline were found in 0.9% of tests and noise deviations greater than 5% from baseline were found in 1% of tests. The phantom was shown to be sensitive to changes in AEC setup, including the use of 3D, longitudinal or rotational tube current modulation. This test methodology allows for continuing performance assessment of CT AEC systems, and we recommend that this test should become part of routine CT quality assurance programs. Tolerances of ± 15% for CTDIvol and ± 5% for image noise relative to baseline values should be used.

Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood.

UNLABELLED: Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention. IMPORTANCE: Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need.

Detection of polydimethylsiloxanes transferred from silicone-coated parchment paper to baked goods using direct analysis in real time mass spectrometry.

The non-stick properties of parchment papers are achieved by polydimethylsiloxane (PDMS) coatings. During baking, PDMS can thus be extracted from the silicone-coated parchment into the baked goods. Positive-ion direct analysis in real time (DART) mass spectrometry (MS) is highly efficient for the analysis of PDMS. A DART-SVP source was coupled to a quadrupole-time-of-flight mass spectrometer to detect PDMS on the contact surface of baked goods after use of silicone-coated parchment papers. DART spectra from the bottom surface of baked cookies and pizzas exhibited signals because of PDMS ions of the general formula [(C2H6SiO)n + NH4 ](+) in the m/z 800-1900 range.

Analysis of a parent-initiated social media campaign for Hirschsprung's disease.

BACKGROUND: Social media can be particularly useful for patients or families affected by rare conditions by allowing individuals to form online communities across the world. OBJECTIVE: Our aim in this study was to conduct a descriptive and quantitative analysis of the use of a social media community for Hirschsprung's Disease (HD). METHODS: In July 2011, a mother of a child with HD launched the "Shit Happens" campaign. The campaign uses social media (blogs, Twitter, and Facebook) to engage other families affected by HD. Internet analytics including Google Analytics and Facebook Insights were used to evaluate the reach and responsiveness of this campaign. RESULTS: On the day the HD campaign was launched, 387 people viewed the blog "Roo's Journey". Blog views have now exceeded 5400 views from 37 countries. The Facebook page extends to 46 countries, has an average post reach of 298 users, 1414 "likes", and an overall reach of 131,032 users. The campaign has 135 Twitter followers and 344 tweets at the time of writing. The most common question posted on the Facebook page is related to treatment for extreme diaper rash. Responsiveness assessment demonstrated that within 2 hours of posting, a question could receive 143 views and 20 responses, increasing to 30 responses after 5 hours. CONCLUSIONS: Social media networks are well suited to discussion, support, and advocacy for health-related conditions and can be especially important in connecting families affected by rare conditions. The HD campaign demonstrates the reach and responsiveness of a community that primarily relies on social media to connect families affected by HD. Although responsive, this community is currently lacking consistent access to evidence-based guidance for their common concerns. We will explore innovative consumer-researcher partnerships to offer a solution in future research.

Characterization of volatile and semi-volatile compounds in green and fermented leaves of Bergenia crassifolia L. by gas chromatography-mass spectrometry and ID-CUBE direct analysis in real time-high resolution mass spectrometry.

Chemical compositions of volatile and semi-volatile components in green and fermented leaves of Bergenia crassifolia L. were studied. Leaf components were identified using gas chromatography with low resolution mass spectrometry and direct analysis in real time (DART) high resolution mass spectrometry with an ID-CUBE ion source. Phytol, nerolidol, geraniol, linalool, alpha-bisabolol, alpha-bisabololoxide B, alpha-cadinol, delta-cadinene, alpha-terpineol and several other marker compounds of special interest were defined, for which the process of fermentation significantly changed their content in the leaves. Low resolution El GC-MS and ID-CUBE DART-HRMS were found to be complementary methods, as they provide different information, helpful to increase the confidence of identification.

Analyzing discharge strategies during acute care: a discrete-event simulation study.

BACKGROUND: We developed a discrete-event simulation model of patient pathway through an acute care hospital that comprises an ED and several inpatient units. The effects of discharge timing on ED waiting and boarding times, ambulance diversions, leave without treatment, and readmissions were explicitly modeled. We then analyzed the impact of 1 static and 2 proactive discharge strategies on these system outcomes. RESULTS: Our analysis indicated that although the 2 proactive discharge strategies significantly reduced ED waiting and boarding times, and several other measures, compared with the static strategy (P < 0.01), the number of readmissions increased substantially. Further analysis indicated that these findings are sensitive to changes in patient arrival rate and conditions for ambulance diversion. CONCLUSIONS: Determining the appropriate time to discharge patients not only can affect individual patients' health outcomes, but also can affect various aspects of the hospital. The study improves our understanding of how individual inpatient discharge decisions can be objectively viewed in terms of their impact on other operations, such as ED crowding and readmission, in an acute care hospital.

A systematic review of the benefits of mindfulness-based interventions following transient ischemic attack and stroke.

BACKGROUND: Recent epidemiological studies have demonstrated an association between perceived psychological stress and ischemic stroke. A feature of stroke is recurrence; 30-40% within five-years following first transient ischemic attack/stroke. Equipping patients with skills and coping strategies to help reduce or manage perceived psychological stress may represent an important secondary prevention intervention. Mindfulness-based interventions are structured, group-based self-management programmes with potential to help people with long-term conditions cope better with physical, psychological, or emotional distress. Review evidence suggests significant benefits across a range of physical and mental health problems. However, we could find no evidence synthesis relating specifically to the benefits of mindfulness-based interventions following transient ischemic attack/stroke. AIM: The review aims to evaluate the benefits of mindfulness-based interventions following transient ischemic attack/stroke. METHODS: Six major databases were searched using subject headings and key words. Papers were screened using review-specific criteria. Critical appraisal and data extraction were conducted independently by two reviewers. Statistical meta-analysis was not possible; therefore findings are presented in narrative form. RESULTS: Four studies involving 160 participants were reviewed. Three papers reported mindfulness-based interventions delivered to groups; one paper reported a mindfulness-based intervention which was delivered one to one. The results demonstrate a positive trend in favor of the benefits of mindfulness-based interventions across a range of psychological, physiological, and psychosocial outcomes including anxiety, depression, mental fatigue, blood pressure, perceived health, and quality of life. No evidence of harm was found. CONCLUSION: Following transient ischemic attack/stroke, people may derive a range of benefits from mindfulness-based interventions; however, further methodologically robust trials are required.