Pancreatic Plasmacytoma: A Case of Recurrent Disease.

Pancreatic plasmacytoma is a rare entity of extramedullary plasmacytomas (EMP). It is important to consider pancreatic plasmacytoma in patients diagnosed with multiple myeloma (MM) presenting with obstructive jaundice. We present a case of pancreatic plasmacytoma in a patient with previously diagnosed multiple myeloma and extramedullary plasmacytoma in remission. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) were of great diagnostic and therapeutic value for acute management.

TdT Positive Lymphoma with MYC, BCL2 and BCL6 Rearrangements: A Review of Diagnosis and Treatment.

In the modern era, classification of neoplasms not only depends on immunomorphological features but also on specific disease-defining genetic events. Translocations/rearrangements of MYC/8q24 locus combined with BCL-2 or BCL6 translocations (double/triple hit) are considered hallmarks of high-grade B-cell lymphoma (HGBL), a type of aggressive mature B-cell lymphoma. When cases with immature immunophenotypes present these rearrangements, diagnosis becomes very difficult. We herein report an unusual case of an aggressive B-cell lymphoma/leukemia that presented with immature morphology and immunophenotype with triple hit gene rearrangements. This case highlights the difficulty in classifying and appropriately treating these patients. The novel aspect is the treatment and outcome with chimeric antigen receptor or CAR T-cell therapy.

Detection of Topological Spin Textures via Nonlinear Magnetic Responses.

Topologically nontrivial spin textures, such as skyrmions and dislocations, display emergent electrodynamics and can be moved by spin currents over macroscopic distances. These unique properties and their nanoscale size make them excellent candidates for the development of next-generation race-track memory and unconventional computing. A major challenge for these applications and the investigation of nanoscale magnetic structures in general is the realization of suitable detection schemes. We study magnetic disclinations, dislocations, and domain walls in FeGe and reveal pronounced responses that distinguish them from the helimagnetic background. A combination of magnetic force microscopy (MFM) and micromagnetic simulations links the response to the local magnetic susceptibility, that is, characteristic changes in the spin texture driven by the MFM tip. On the basis of the findings, which we explain using nonlinear response theory, we propose a read-out scheme using superconducting microcoils, presenting an innovative approach for detecting topological spin textures and domain walls in device-relevant geometries.

Digital Dementia Registry Bavaria-digiDEM Bayern: study protocol for a multicentre, prospective, longitudinal register study.

INTRODUCTION: Dementia is one of the most relevant widespread diseases, with a prevalence of currently 50 million people with dementia worldwide. The care of people with dementia will be one of the major challenges for healthcare systems worldwide. Digitalisation offers new possibilities to improve both dementia healthcare and health outcomes research as a fundament for national healthcare planning. The 'Digital Dementia Registry Bavaria-digiDEM Bayern' aims to improve the understanding of the complexity and long-term progression of dementia and the current care situation in Bavaria. Moreover, by offering digital services, digiDEM will actively contribute to improving the care situation in Bavaria. METHODS AND ANALYSIS: digiDEM will recruit people with dementia and their family caregivers in all administrative regions of Bavaria. All participants will undergo dementia screening prior to study inclusion in order to identify people with mild cognitive impairment and mild-to-moderate dementia. Participants will be followed up over a period of three years. Sociodemographic data, type of dementia, symptoms, diagnosis, cognitive trajectories, activities of daily living, behavioural and psychological symptoms, falls, resource utilisation, caregiver burden, quality of life, needs of people with dementia and their caregivers, mobility, use of media and sources of information will be assessed. The project will implement a digital web-based platform for data collection. Data will be collected by means of standardised online or face-to-face interviews. ETHICS AND DISSEMINATION: The study obtained ethical approval from the Ethics Committee of the Medical Faculty of Friedrich-Alexander-University Erlangen-Nürnberg (FAU) (application number: 253_20 B). Findings will be used for evidence-based decision-making for health decision-makers in order to optimise dementia healthcare in the state of Bavaria. Specific analyses will be conducted for the participating research partners. Results of the study will be published in peer-reviewed journals.

An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability.

Proteins of the Fanconi Anemia (FA) complementation group are required for crosslink (CL) repair in humans and their loss leads to severe pathological phenotypes. Here we characterize a homolog of the Fe-S cluster helicase FANCJ in the model plant Arabidopsis, AtFANCJB, and show that it is involved in interstrand CL repair. It acts at a presumably early step in concert with the nuclease FAN1 but independently of the nuclease AtMUS81, and is epistatic to both error-prone and error-free post-replicative repair in Arabidopsis. The simultaneous knock out of FANCJB and the Fe-S cluster helicase RTEL1 leads to induced cell death in root meristems, indicating an important role of the enzymes in replicative DNA repair. Surprisingly, we found that AtFANCJB is involved in safeguarding rDNA stability in plants. In the absence of AtRTEL1 and AtFANCJB, we detected a synergetic reduction to about one third of the original number of 45S rDNA copies. It is tempting to speculate that the detected rDNA instability might be due to deficiencies in G-quadruplex structure resolution and might thus contribute to pathological phenotypes of certain human genetic diseases.

Non-rhythmic head-direction cells in the parahippocampal region are not constrained by attractor network dynamics.

Computational models postulate that head-direction (HD) cells are part of an attractor network integrating head turns. This network requires inputs from visual landmarks to anchor the HD signal to the external world. We investigated whether information about HD and visual landmarks is integrated in the medial entorhinal cortex and parasubiculum, resulting in neurons expressing a conjunctive code for HD and visual landmarks. We found that parahippocampal HD cells could be divided into two classes based on their theta-rhythmic activity: non-rhythmic and theta-rhythmic HD cells. Manipulations of the visual landmarks caused tuning curve alterations in most HD cells, with the largest visually driven changes observed in non-rhythmic HD cells. Importantly, the tuning modifications of non-rhythmic HD cells were often non-coherent across cells, refuting the notion that attractor-like dynamics control non-rhythmic HD cells. These findings reveal a new population of non-rhythmic HD cells whose malleable organization is controlled by visual landmarks.

Hippocampal Remapping and Its Entorhinal Origin.

The activity of hippocampal cell ensembles is an accurate predictor of the position of an animal in its surrounding space. One key property of hippocampal cell ensembles is their ability to change in response to alterations in the surrounding environment, a phenomenon called remapping. In this review article, we present evidence for the distinct types of hippocampal remapping. The progressive divergence over time of cell ensembles active in different environments and the transition dynamics between pre-established maps are discussed. Finally, we review recent work demonstrating that hippocampal remapping can be triggered by neurons located in the entorhinal cortex.

Risk-Cost Estimation of On-Site Wastewater Treatment System Failures Using Extreme Value Analysis.

Owner resistance to increasing regulation of on-site wastewater treatment systems (OWTS), including obligatory inspections and upgrades, moratoriums and cease-and-desist orders in communities around the U.S. demonstrate the challenges associated with managing risks of inadequate performance of owner-operated wastewater treatment systems. As a result, determining appropriate and enforceable performance measures in an industry with little history of these requirements is challenging. To better support such measures, we develop a statistical method to predict lifetime failure risks, expressed as costs, in order to identify operational factors associated with costly repairs and replacement. A binomial logistic regression is used to fit data from public records of reported OWTS failures, in Boulder County, Colorado, which has 14 300 OWTS to determine the probability that an OWTS will be in a low- or high-risk category for lifetime repair and replacement costs. High-performing or low risk OWTS with repairs and replacements below the threshold of $9000 over a 40-year life are associated with more frequent inspections and upgrades following home additions. OWTS with a high risk of exceeding the repair cost threshold of $18 000 are further analyzed in a variation of extreme value analysis (EVA), Points Over Threshold (POT) where the distribution of risk-cost exceedance values are represented by a generalized Pareto distribution. The resulting threshold cost exceedance estimates for OWTS in the high-risk category over a 40-year expected life ranged from $18 000 to $44 000.

Modeling on-site wastewater treatment system performance fragility to hydroclimate stressors.

Increasing variability of climate-related factors, especially precipitation and temperature, poses special risks to on-site wastewater treatment systems (OWTS), which depend on subsurface saturation conditions for treatment and dispersion of wastewater. We assess OWTS fragility - the degree to which a system loses functionality - as a step to characterizing the resilience of residential wastewater treatment systems. We used the frequency and indexed severity of OWTS failures and resulting repairs to quantify fragility as a function of hydroclimate variables, including precipitation, temperature and stream flow. The frequency of each category of repair (minor, moderate and major) for 225 OWTS obtained from Boulder County public health records was modeled as a function of climate factors using a generalized linear model with a Poisson distribution link function. The results show that prolonged precipitation patterns, with monthly rainfall >10.16 cm, influence OWTS fragility, and complete loss of OWTS functionality, requiring replacement, is impacted by high temperatures, frequency of wetter-than-normal months, and the magnitude of peak stream flow in the watershed. Weather-related covariates explained 70% of the variability in OWTS major repair data between 1979 and 2006. These results indicate that fragility arising from climate factors, and associated costs to owners, environmental and health impacts, should be considered in planning, design and operation of OWTS.

Visual landmarks sharpen grid cell metric and confer context specificity to neurons of the medial entorhinal cortex.

Neurons of the medial entorhinal cortex (MEC) provide spatial representations critical for navigation. In this network, the periodic firing fields of grid cells act as a metric element for position. The location of the grid firing fields depends on interactions between self-motion information, geometrical properties of the environment and nonmetric contextual cues. Here, we test whether visual information, including nonmetric contextual cues, also regulates the firing rate of MEC neurons. Removal of visual landmarks caused a profound impairment in grid cell periodicity. Moreover, the speed code of MEC neurons changed in darkness and the activity of border cells became less confined to environmental boundaries. Half of the MEC neurons changed their firing rate in darkness. Manipulations of nonmetric visual cues that left the boundaries of a 1D environment in place caused rate changes in grid cells. These findings reveal context specificity in the rate code of MEC neurons.