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Autophagy plays a vital role in tumor therapy and survival of dormant tumor cells. Here we describe a novel function of a protein known as Transmembrane 219 (TM219) as an autophagy activator. TM219 is a small membrane protein expressed in all known human tissues except the thymus. We used biochemical approaches to identify calmodulin and calmodulin dependent protein kinase II as a part of TM219 protein complex. Then, we employed in vitro reconstitution system and fluorescence anisotropy to study the requirements of TM219 to bind calmodulin in vitro. We also used this system to study the effects of a synthetic peptide derived from the sequence of the short cytoplasmic tail of TM219 (SCTT) on calmodulin-TM219 receptor interactions. We conjugated SCTT peptide with a pH Low Insertion peptide (pHLIP) for optimal cellular delivery. We finally tested the effects of SCTT-pHLIP on triple negative human breast cancer cells in three dimension culture. Our data defined a novel function of TM219 protein and an efficient approach to inhibit it.

Evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened the concern that true rates of myocardial infarctions have been under-ascertained and left untreated. We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States (US) between January 1, 2020 and April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS cardiovascular activations. After multivariable adjustment, increasing COVID-19 rates were associated with less activations for chest pain and non-ST-elevation myocardial infarctions. Simultaneously, increasing COVID-19 rates were associated with more activations for cardiac arrests, ventricular fibrillation, and ventricular tachycardia. Although direct effects of COVID-19 infections may explain these discordant observations, these findings may also arise from patients delaying or avoiding care for myocardial infarction, leading to potentially lethal consequences.

In the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission. We conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys. Among 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ratio [OR] 1.75, 95% CI 1.39-2.20, p<0.001), anemia (OR 1.45, 95% CI 1.16-1.81, p = 0.001), hypertension (OR 1.35, 95% CI 1.08-1.68, p = 0.007), cigarette smoking in the last 30 days (OR 1.86, 95% CI 1.35-2.55, p<0.001), any viral symptoms among household members 6-12 days prior (OR 2.06, 95% CI 1.67-2.55, p<0.001), and the maximum number of individuals the participant interacted with within 6 feet in the past 6-12 days (OR 1.15, 95% CI 1.06-1.25, p<0.001) were each associated with a higher risk of developing viral symptoms. Conversely, a higher subjective social status (OR 0.87, 95% CI 0.83-0.93, p<0.001), at least weekly exercise (OR 0.57, 95% CI 0.47-0.70, p<0.001), and sanitizing one's phone (OR 0.79, 95% CI 0.63-0.99, p = 0.037) were each associated with a lower risk of developing viral symptoms. While several immutable characteristics were associated with the risk of developing viral symptoms, multiple immediately modifiable exposures and habits that influence risk were also observed, potentially identifying readily accessible strategies to mitigate risk in the COVID-19 era.

ObjectiveUntil effective treatments and vaccines are made readily and widely available, preventative behavioural health measures will be central to the SARS-CoV-2 public health response. While current recommendations are grounded in general infectious disease prevention practices, it is still not entirely understood which particular behaviours or exposures meaningfully affect one’s own risk of incident SARS-CoV-2 infection. Our objective is to identify individual-level factors associated with one’s personal risk of contracting SARS-CoV-2.DesignProspective cohort study of adult participants from 26 March 2020 to 8 October 2020.SettingThe COVID-19 Citizen Science Study, an international, community and mobile-based study collecting daily, weekly and monthly surveys in a prospective and time-updated manner.ParticipantsAll adult participants over the age of 18 years were eligible for enrolment.Primary outcome measureThe primary outcome was incident SARS-CoV-2 infection confirmed via PCR or antigen testing.Results28 575 unique participants contributed 2 479 149 participant-days of data across 99 different countries. Of these participants without a history of SARS-CoV-2 infection at the time of enrolment, 112 developed an incident infection. Pooled logistic regression models showed that increased age was associated with lower risk (OR 0.98 per year, 95% CI 0.97 to 1.00, p=0.019), whereas increased number of non-household contacts (OR 1.10 per 10 contacts, 95% CI 1.01 to 1.20, p=0.024), attending events of at least 10 people (OR 1.26 per 10 events, 95% CI 1.07 to 1.50, p=0.007) and restaurant visits (OR 1.95 per 10 visits, 95% CI 1.42 to 2.68, p<0.001) were associated with significantly higher risk of incident SARS-CoV-2 infection.ConclusionsOur study identified three modifiable health behaviours, namely the number of non-household contacts, attending large gatherings and restaurant visits, which may meaningfully influence individual-level risk of contracting SARS-CoV-2.

BackgroundCardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease.ObjectiveTo determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis.MethodsAdults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations.ResultsA total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34–126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5–13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia.ConclusionsWe did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

When two rough surfaces are loaded together contact occurs at asperity peaks. An interface of solid contact regions and air gaps is formed that is less stiff than the bulk material. The stiffness of a structure thus depends on the interface conditions; this is particularly critical when high stiffness is required, for example in precision systems such as machine tool spindles. The rough surface interface can be modelled as a distributed spring. For small deformation, the spring can be assumed to be linear; whilst for large deformations the spring gets stiffer as the amount of solid contact increases. One method to measure the spring stiffness, both the linear and nonlinear aspect, is by the reflection of ultrasound. An ultrasonic wave causes a perturbation of the contact and the reflection depends on the stiffness of the interface. In most conventional applications, the ultrasonic wave is low power, deformation is small and entirely elastic, and the linear stiffness is measured. However, if a high-powered ultrasonic wave is used, this changes the geometry of the contact and induces nonlinear response. In previous studies through transmission methods were used to measure the nonlinear interfacial stiffness. This approach is inconvenient for the study of machine elements where only one side of the interface is accessible. In this study a reflection method is undertaken, and the results are compared to existing experimental work with through transmission. The variation of both linear and nonlinear interfacial stiffnesses was measured as the nominal contact pressure was increased. In both cases interfacial stiffness was expressed as nonlinear differential equations and solved to deduce the contact pressure-relative surface approach relationships. The relationships derived from linear and nonlinear measurements were similar, indicating the validity of the presented methods.

In a randomized trial, coffee consumption was not associated with more premature atrial contractions than caffeine avoidance but was associated with more premature ventricular contractions and daily steps and less sleep.

In the United States, police officers are involved in approximately 1,000 deadly shooting incidents each year. Involved officers are often psychologically impacted by the trauma exposure stemming from these incidents. Acute trauma exposure among officers is associated with increased rates of depression, posttraumatic stress disorder (PTSD), alcoholism, and suicidal ideation. When confronted with acute stress, the sympathetic nervous system initiates a fight-or-flight response that creates a cascade of physiological activity as part of the body’s natural adaptive effort to perceive and survive threats. This physiological activity can contribute to posttraumatic stress and, in some cases, diagnosable mental health disorders. Accordingly, officer-involved shootings, especially those resulting in a fatality, potentially create substantial disruption in the lives of officers. Forms of disruption include changes in daily routine, assignment, and duty status. More significantly, some officers find themselves reconciling a new self-conception that challenges their identity as one who protects life with their new reality of taking a life. Considering this post-shooting experience, how can law enforcement agencies promote officer well-being in the aftermath of a fatal shooting? Though there are no one-size-fits-all solutions, law enforcement agency policies and practices that guide officer-involved shooting investigations and interventions should be ameliorative, trauma-informed, and designed to support officer identity. This case study analyzes 10 fatal officer-involved shooting incidents and based on within-case and cross-case analyses offers a dozen specific recommendations on how law enforcement agencies can better support officers coping in the aftermath of such events. Six recommendations primarily address policies and practices concerning an agency’s immediate response to and management of the shooting scene. These recommendations entail transporting officers and offenders to separate hospitals, when feasible; allowing involved officers, if able, to notify their loved ones; providing involved officers with transportation until their first sleep cycle; identity-informed practices for recovering and replacing an officer’s firearm(s); supportive and frequent communication from the chain of command at the scene as well as in the months following the incident; and minimizing an involved officer’s post-shooting exposure to the scene. The remaining six recommendations pertain to agency policies and practices regarding the treatment of involved officers in the days, weeks, and months following the incident. These six recommendations include requiring a minimum of three days of paid administrative leave; mandating at least one counseling session with a mental health professional; prohibiting mandatory fitness for duty evaluations; assessing the need for and providing eye movement desensitization and reprocessing (EMDR) therapy when appropriate; offering counseling services to family members of officers; and not issuing Miranda warnings when conducting a noncustodial interview of a shooting officer. Agency implementation of these measures will assist officers in coping with the psychological and emotional challenges frequently experienced in the aftermath of a fatal police-involved shooting.

The focus of this thesis is the development of a measurement process to accurately record the non-linear hysteretic susceptibility and magnetostriction of ferromagnetic materials. On voyage, naval vessels will endure tremendous changes in magnetic or mechanical stress due to maneuvering and wave motion in the earth’s magnetic fields as well as continual changes in hydro-dynamic stresses. Such changes in stress change the magnetic properties of the steel, impacting the ship signature. This research aims at providing the ability to predict the changes in the magnetic properties of steels undergoing dynamic changes in magnetic and mechanical stresses. Doing so will facilitate the prediction and removal of magnetic signatures from naval vessels – providing the cloaking from underwater sensors that is essential to the survival of the vessel. Novel experimental methods have been developed in the CU Denver magnetics laboratory using a Faraday coil measurement system. These methods have enabled the accurate prediction of the essential physical parameters needed to predict non-linear susceptibility of mild steels as a function of magnetic fields and axial mechanical stresses. The apparatus and experimental results will be presented demonstrating the capabilities of the measurement system.

[...]the Eritrean refugee inflow into Ethiopia has grown to seven times its pre-rapprochement level. With a lower incidence of P. vivax malaria and no history of dealing with in-migration, Eritrea will be hit hard as new infectious cases cross the border. Since Eritreans have less exposure and poorer immunity to P. vivax, Ethiopia’s own vivax malaria incidence will rise as it takes in at-risk individuals. Ethiopia and Eritrea must build a stronger approach to control in order to address migration’s challenges. Since research on malaria has heavily focused on P. falciparum, Ethiopia and Eritrea must address the P. vivaxissue with policies and control methods that reflect the boundary-defying nature of the parasite.