Nodes, paranodes and neuropathies

This review summarises recent evidence supporting the involvement of the specialised nodal and perinodal domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammatory, peripheral neuropathies.The identification of new target antigens in the inflammatory neuropathies heralds a revolution in diagnosis, and has already begun to inform increasingly targeted and individualised therapies. Rapid progress in our basic understanding of the highly specialised nodal regions of peripheral nerves serves to strengthen the links between their unique microstructural identities, functions and pathologies. In this context, the detection of autoantibodies directed against nodal and perinodal targets is likely to be of increasing clinical importance. Antiganglioside antibodies have long been used in clinical practice as diagnostic serum biomarkers, and associate with specific clinical variants but not to the common forms of either acute or chronic demyelinating autoimmune neuropathy. It is now apparent that antibodies directed against several region-specific cell adhesion molecules, including neurofascin, contactin and contactin-associated protein, can be linked to phenotypically distinct peripheral neuropathies. Importantly, the immunological characteristics of these antibodies facilitate the prediction of treatment responsiveness

Probing Light Atoms at Sub-nanometer Resolution: Realization of Scanning Transmission Electron Microscope Holography

Atomic resolution imaging in transmission electron microscopy (TEM) and scanning TEM (STEM) of light elements in electron-transparent materials has long been a challenge. Biomolecular materials, for example, are rapidly altered when illuminated with electrons. These issues have driven the development of TEM and STEM techniques that enable the structural analysis of electron beam-sensitive and weakly scattering nano-materials. Here, we demonstrate such a technique, STEM holography, capable of absolute phase and amplitude object wave measurement with respect to a vacuum reference wave. We use an amplitude-dividing nanofabricated grating to prepare multiple spatially separated electron diffraction probe beams focused at the sample plane, such that one beam transmits through the specimen while the others pass through vacuum. We raster-scan the diffracted probes over the region of interest. We configure the post specimen imaging system of the microscope to diffraction mode, overlapping the probes to form an interference pattern at the detector. Using a fast-readout, direct electron detector, we record and analyze the interference fringes at each position in a 2D raster scan to reconstruct the complex transfer function of the specimen, t(x). We apply this technique to image a standard target specimen consisting of gold nanoparticles on a thin amorphous carbon substrate, and demonstrate 2.4 angstrom resolution phase images. We find that STEM holography offers higher phase-contrast of the amorphous material while maintaining Au atomic lattice resolution when compared with high angle annular dark field STEM.Comment: 9 pages, 5 figures in main text, 1 supplemental figure in the appendi

Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as negative for intraepithelial lesion, the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01-338.62; p \u3c 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher\u27s exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors. Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed

Pastoralist Use of Reseeded Fields for Additional Resilience to Climate Variability through Alternate Livelihood Activities

Land degradation, climate variability, socio-economic changes and population increase are some of the factors that shrink grazing lands making forage availability less predictable and affecting the resilience of pastoralists communities. Reseeding as an intervention can rehabilitate degraded lands for profitable use through offering pastoralists alternative sources of livelihood and encourage livelihood diversification. This study evaluated two pastoral communities, the Tugen and the Njemps from Baringo County, Kenya, who have owned, managed and used reseeded fields to study the dynamics of reseeding land. A total of 193 pastoralist households were interviewed. These two pastoral communities used their fields for: dry season grazing, grass seed harvesting, cutting thatching grass, milking of mostly cattle, engaging in fattening programs, bailing of hay, and leasing of land. On average, each household engaged in two to three activities with a maximum of five activities combined. The most common activity was dry season grazing which is practiced by 82% of the respondents followed by grass seed harvesting. These activities can be performed in sequence but proper planning is required to ensure that the field remains sustainably productive and successful. Reseeding appears to have high potential for implementation in other dry land counties of Kenya and Sub-Saharan Africa as an intervention that can improve resilience to climate variability as it provides additional grazing ground for the livestock

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BackgroundThe risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria").MethodsRetrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG).ResultsAfter exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001).ConclusionsThis study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk

Conceptual diagrams: representing ideas in design

Studies in cognition In many studies of well-defined problems, diagrammatic representations illustrate either causal or temporal relationships between parts of entities and phenomena that the diagram represents. In architecture, diagrams are used to represent causal relationships, such as with orientation diagrams, or temporal relationships, such as with circulation diagrams. There is, however, another kind of diagram that is used to represent the main idea or the core of a design. We call these diagrams conceptual diagrams. They differ, potentially, from other diagrammatic representations studied thus far in that they represent an abstract conceptualization of a potential problem solution. Diagrams in other fields can be interpreted as conceptual diagrams as well, such as a diagram that shows the electron orbiting around a nucleus in atomic physics, or the supply-demand diagram in economics. In the domain of scientific discovery, Nersessian Conceptual diagrams are abstract representations that embed the core of a conceptualization of a problem solution. They are concise, yet powerful aids in problem solving in that they provide high-level commitments constraining solutions. In architecture, they embed the core of a design solution encapsulating its generic characteristics and constraints and conveying the form of possible specific solutions. That they are not detailed prevents early commitment to a specific design solution and, thus, they facilitate exploratory reasoning. At the same time they are not ambiguous in the way sketches are in that they fix meaning and define a set of related solutions. This latter is important because design problems are ill-defined in that either the initial state, the goal state, or the operators--or all of them--require further specification. With ill-defined problems there exists a set of potential goal states instead of one goal state. One way that architects delimit the range of alternatives is by analogy. Conceptual diagrams function in a way similar to analogies in that they provide constraints that restrict the set of specified goal states. We propose salient characteristics of conceptual diagrams that are significant fo

Interpretable and efficient contrast in scanning transmission electron microscopy with a diffraction grating beamsplitter

Efficient imaging of biomolecules, 2D materials and electromagnetic fields depends on retrieval of the phase of transmitted electrons. We demonstrate a method to measure phase in a scanning transmission electron microscope using a nanofabricated diffraction grating to produce multiple probe beams. The measured phase is more interpretable than phase-contrast scanning transmission electron microscopy techniques without an off-axis reference wave, and the resolution could surpass that of off-axis electron holography. We apply the technique to image nanoparticles, carbon sub- strates and electric fields. The contrast observed in experiments agrees well with contrast predicted in simulations

COVID-19 Vaccine Hesitancy among Arab Americans

Background: Coronavirus disease-2019 (COVID-19) vaccines have a significant impact on reducing morbidity and mortality from infection. However, vaccine hesitancy remains an obstacle in combating the pandemic. The Arab American (AA) population is understudied; thus, we aimed to explore COVID-19 attitudes within this community. Methods: This was a cross-sectional study. An anonymous online survey was distributed to members of different AA associations and to the community through the snowball method. Results: A total of 1746 participants completed the survey. A total of 92% of respondents reported having received at least one dose of a COVID-19 vaccine. A total of 73% reported willingness to receive a booster, and 72% plan to give their children the vaccine. On multivariate analysis, respondents were more likely to be vaccine-hesitant if they were hesitant about receiving any vaccine in general. They were less likely to be vaccine-hesitant if they were immigrants, over the age of 40, up to date on their general vaccination and if they believed that COVID-19 vaccines are safe and effective in preventing an infection. The belief that all vaccines are effective at preventing diseases was also associated with lower hesitancy. Conclusions: This sample of AAs have higher vaccination rates and are more willing to vaccinate their children against COVID-19 when compared to the rest of the population. However, a reemergence of hesitancy might be arising towards the boosters

Clinical Characteristics of Breast Cancers in African‐American Women with Benign Breast Disease: A Comparison to the Surveillance, Epidemiology, and End Results Program

Benign breast disease ( BBD ) is a very common condition, diagnosed in approximately half of all A merican women throughout their lifecourse. White women with BBD are known to be at substantially increased risk of subsequent breast cancer; however, nothing is known about breast cancer characteristics that develop after a BBD diagnosis in A frican‐ A merican women. Here, we compared 109 breast cancers that developed in a population of A frican‐ A merican women with a history of BBD to 10,601 breast cancers that developed in a general population of A frican‐ A merican women whose cancers were recorded by the M etropolitan D etroit C ancer S urveillance S ystem ( MDCSS population). Demographic and clinical characteristics of the BBD population were compared to the MDCSS population, using chi‐squared tests, F isher's exact tests, t ‐tests, and W ilcoxon tests where appropriate. K aplan– M eier curves and Cox regression models were used to examine survival. Women in the BBD population were diagnosed with lower grade (p = 0.02), earlier stage cancers (p = 0.003) that were more likely to be hormone receptor‐positive (p = 0.03) compared to the general metropolitan Detroit A frican‐ A merican population. In situ cancers were more common among women in the BBD cohort (36.7%) compared to the MDCSS population (22.1%, p < 0.001). Overall, women in the BBD population were less likely to die from breast cancer after 10 years of follow‐up (p = 0.05), but this association was not seen when analyses were limited to invasive breast cancers. These results suggest that breast cancers occurring after a BBD diagnosis may have more favorable clinical parameters, but the majority of cancers are still invasive, with survival rates similar to the general A frican‐ A merican population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109284/1/tbj12331.pd