On Operations Friedman, Brett
2021, 2021-10-15
eBook
On Operations: Operational Art and Military Disciplines traces the history of the development of military staffs and ideas on the operational level of war and operational art from the Napoleonic Wars ...to today, viewing them through the lens of Prussia/Germany, the Soviet Union, and the United States.
The inner ear has fluid-filled compartments of different ionic compositions, including the endolymphatic and perilymphatic spaces of the organ of Corti; the separation from one another by epithelial ...barriers is required for normal hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ) protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues. We show that, in humans, four different recessive mutations of TRIC cause nonsyndromic deafness (DFNB49), a surprisingly limited phenotype, given the widespread tissue distribution of tricellulin in epithelial cells. In the inner ear, tricellulin is concentrated at the tricellular TJs in cochlear and vestibular epithelia, including the structurally complex and extensive junctions between supporting and hair cells. We also demonstrate that there are multiple alternatively spliced isoforms of TRIC in various tissues and that mutations of TRIC associated with hearing loss remove all or most of a conserved region in the cytosolic domain that binds to the cytosolic scaffolding protein ZO-1. A wild-type isoform of tricellulin, which lacks this conserved region, is unaffected by the mutant alleles and is hypothesized to be sufficient for structural and functional integrity of epithelial barriers outside the inner ear.
Objective
To measure the extent to which the provision of mammograms was impacted by the COVID‐19 pandemic and surrounding guidelines.
Data Sources
De‐identified summary data derived from medical ...claims and eligibility files were provided by Independence Blue Cross for women receiving mammograms.
Study Design
We used a difference‐in‐differences approach to characterize the change in mammograms performed over time and a queueing formula to estimate the time to clear the queue of missed mammograms.
Data Collection
We used data from the first 30 weeks of each year from 2018 to 2020.
Principal Findings
Over the 20 weeks following March 11, 2020, the volume of screening mammograms and diagnostic mammograms fell by 58% and 38% of expected levels, on average. Lowest volumes were observed in week 15 (April 8 to 14), when screening and diagnostic mammograms fell by 99% and 74%, respectively. Volumes began to rebound in week 19 (May), with diagnostic mammograms reaching levels to similar to previous years’ and screening mammograms remaining 14% below expectations. We estimate it will take a minimum of 22 weeks to clear the queue of missed mammograms in our study sample.
Conclusions
The provision of mammograms has been significantly disrupted due to the COVID‐19 pandemic.
A clinical and biological review of keratoacanthoma Tisack, A.; Fotouhi, A.; Fidai, C. ...
British journal of dermatology (1951),
September 2021, 2021-09-00, 20210901, Letnik:
185, Številka:
3
Journal Article
Recenzirano
Summary
Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, a KA manifests as a rapidly ...growing, well‐differentiated, squamoid lesion with a predilection for sun‐exposed sites in elderly people and a tendency to spontaneously regress. Historically, KAs have been considered a variant of cutaneous squamous cell carcinoma (cSCC) and are often reported as KA‐type cSCC. However, the penchant for regression has led many to categorize KAs as biologically benign tumours with distinct pathophysiological mechanisms from malignant cSCC. The clinical and histopathological similarities between KA and cSCC, particularly the well‐differentiated variant of cSCC, have made definitive differentiation difficult or impossible in many cases. The ambiguity between entities has led to the general recommendation for surgical excision of KAs to ensure a potentially malignant cSCC is not left untreated. This current standard creates unnecessary surgical morbidity and financial strain for patients, especially the at‐risk elderly population. There have been no reports of death from a definitive KA to date, while cSCC has an approximate mortality rate of 1·5%. Reliably distinguishing cSCC from KA would shift management strategies for KAs towards less‐invasive treatment modalities, prevent unnecessary surgical morbidity, and likely reduce associated healthcare costs. Herein, we review the pathophysiology and clinical characteristics of KA, and conclude on the balance of current evidence that KA is a benign lesion and distinct from cSCC.
Plain language summary available online
A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided ...experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adequate functional literacy skills positively influence individuals' ability to take control of their health. Print and Web-based cancer information is often written at difficult reading levels. ...This systematic review evaluates readability instruments (FRE, F-K, Fog, SMOG, Fry) used to assess print and Web-based cancer information and word recognition and comprehension tests (Cloze, REALM, TOFHLA, WRAT) that measure people's health literacy. Articles on readability and comprehension instruments explicitly used for cancer information were assembled by searching MEDLINE and PsycINFO from 1993 to 2003. In all, 23 studies were included; 16 on readability, 6 on comprehension, and 1 on readability and comprehension. Of the readability investigations, 14 focused on print materials, and 2 assessed Internet information. Comprehension and word recognition measures were not applied to Web-based information. None of the formulas were designed to determine the effects of visuals or design factors that could influence readability and comprehension of cancer education information.
Individuals' stress in responding to the current COVID-19 pandemic may be exacerbated by information uncertainty driven by inconsistent, unverified, and conflicting news from various sources. The ...current study aims to test if information uncertainty during the COVID-19 outbreak was related to acute stress disorder (ASD) over and above other psychosocial stressors.
An anonymous online survey was conducted with 7800 college students throughout China from January 31 through February 11, 2020. Existing scales were modified to measure ASD and six potential stressors including information uncertainty during the COVID-19 outbreak. Hierarchical regression analysis was conducted to assess the unique association of information uncertainty with ASD. To minimize the effect of large sample size and also to get a sense of whether the effects of information uncertainty were similar to people at the center of the epidemic, we repeated the hierarchical regression among 10% of the students who were randomly selected from the entire sample ("10% random sample"; n = 780) and 226 students from Hubei Province where the outbreak started.
Information uncertainty was highly prevalent among the respondents (64%). It was significantly associated with ASD beyond other key variables and potential stressors across three samples. In the hierarchical regression among the entire sample, demographic variables accounted for 9.4% of the variance in ASD. The other five stressors added 5.1% of the variance. The information uncertainty (β = .159; p < .001) explained an additional 2.1% of the variance. Likewise, the information uncertainty explained an additional 2.1 and 3.4% of the variance in ASD beyond all other variables among the 10% random sample (β = .165; p < .001) and the Hubei sample (β = .196; p < .01), respectively.
Information uncertainty is a unique correlate of psychological stress during the COVID-19 outbreak. Reducing information uncertainty is essential not only for halting virus transmission but also for mitigating negative impacts of the pandemic on people's psychosocial wellbeing. Transparent, timely, and accurate communication can reduce public confusion, fear, and stress. Capacity building in governments, communities, and media outlets to prevent, reduce and manage information uncertainty should be a critical part of the response to an emerging global health crisis such as the COVID-19 pandemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static ...composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca(2+)-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS ...subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co‐segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin‐like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.
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