Missing scalars at the cosmological collider

Light scalar fields typically develop spatially varying backgrounds during inflation. Very often they do not directly affect the density perturbations, but interact with other fields that do leave nontrivial signals in primordial perturbations. In this sense they become “missing scalars” at the cosmological collider. We study potentially observable signals of these missing scalars, focusing on a special example where a missing scalar distorts the usual oscillatory features in the squeezed bispectrum. The distortion is also a useful signal distinguishing the de Sitter background induced thermal mass from a constant intrinsic mass.

Development

Many people describe being musical as a dream that was never realistically attainable because they were not born with the innate talent required. Is this true or can all people become musical? How can they—and their parents and teachers—know if they have “what it takes” to become a musician? These are the kinds of questions addressed by developmental psychology. This chapter explains foundational principles of human music development. It shows that human beings are essentially “hardwired” to be musical, and that there is a predictable progression in which children typically develop musical abilities. Through a combination of factors related to enculturation (informal musical experiences) and education, people develop to a great variety of musical ability levels. The experiences and education received as a child can be very consequential in determining the level of musicality a person will enjoy throughout life.

Folie a Deux: Shared Psychotic Disorder in a Medical Unit

Introduction. A shared psychotic disorder is a system of delusions shared by two or more individuals. Shared psychotic disorders typically develop in pairs or groups with a close relationship who are socially isolated. The function and affect of those inflicted with shared psychotic disorders usually remain intact. For these reasons, a shared psychotic disorder is seldom identified, diagnosed, and treated. This case describes a shared psychotic disorder incidentally discovered in a medical unit. Case. The patient was a 47-year-old woman with no known past psychiatric history who had been medically admitted for gastroenteritis. On the day of discharge, a psychiatric consult was requested for “paranoia and bizarre behavior.” The patient was seen making statements that she needed security and the FBI to escort her as she left the hospital. Another person in the patient’s room was discovered to be the patient’s mother who had been staying with her in the hospital. Evaluation of the patient along with observation of her mother revealed that the two shared a complex system of delusions revealing a diagnosis of shared psychotic disorder. Discussion. A shared psychotic disorder is a unique psychiatric diagnosis. It may be even rarer to diagnose in the inpatient medical setting because multiple individuals from a shared system are typically not seen. In this case, the patient and her mother had multiple clinical characteristics of a shared psychotic disorder, including an enmeshed relationship and social isolation. The treatment for shared psychotic disorders involves separation of the individuals and pharmacotherapy with antipsychotics. This case also presented a unique ethical dilemma as the psychiatric team was called to evaluate a patient and found a patient and another individual to have symptoms. Conclusion. A shared psychotic disorder is important to consider on the differential when cases of psychosis with delusional systems are seen on medical floors.

Combi-Seq: Multiplexed transcriptome-based profiling of drug combinations using 1 deterministic barcoding in single-cell droplets

Anti-cancer therapies often exhibit only short-term effects. Tumors typically develop drug resistance causing relapses that might be tackled with drug combinations. Identification of the right combination is challenging and would benefit from high-content, high-throughput combinatorial screens directly on patient biopsies. However, such screens require a large amount of material, normally not available from patients. To address these challenges, we developed a scalable microfluidic workflow to screen hundreds of drug combinations in picoliter-size droplets using transcriptome changes as a readout for drug effects. We devised a deterministic combinatorial DNA barcoding approach to encode treatment conditions, enabling the gene expression-based readout of drug effects in a highly multiplexed fashion. We applied our method to screen the effect of 420 drug combinations on the transcriptome of K562 cells using only ~250 single cell droplets per condition, to successfully predict synergistic and antagonistic drug pairs, as well as their pathway activities.

Hypereosinophilic syndrome: considerations for the cardiologist

Eosinophil-mediated endomyocardial damage is a well-known complication in patients with hypereosinophilic syndromes (HES). Although management and survival have improved significantly, some patients continue to develop severe cardiomyopathy as a direct consequence of uncontrolled hypereosinophilia. Cardiologists play a key role in early detection and treatment. At the early generally asymptomatic stage, related to subendocardial eosinophilic infiltrates, elevation of the biomarker of cardiac damage (serum troponin) and cardiac MRI are the best tools for diagnosis. As disease progresses, patients typically develop intracardiac mural thrombi and may experience variable degrees of heart failure due to valve damage and/or subendocardial fibrosis, all of which are more readily detectable with traditional echocardiographic investigation. New imaging modalities such as strain imaging and specific sequences in MRI offer the perspective of detecting subtle perturbations and distinguishing inflammatory versus fibrotic stages. Endomyocardial biopsy may help in difficult settings, namely, when blood eosinophilia is not prominent, but may be non-contributive due to sampling issues or eosinophil degranulation or replacement by fibrosis, and must always be performed after careful consideration of the risk:benefit ratio. Although treatment of the HES itself should be managed by clinicians with expertise in this rare disorder with the aim of lowering eosinophil counts to prevent and treat eosinophil-mediated organ damage and dysfunction, cardiologists play a key role in managing the associated cardiopathy. There are no consensual disease-specific guidelines for treating eosinophil-mediated thrombotic complications and cardiopathy, which should be managed according to classical international recommendations.

From Genetics to Histomolecular Characterization: An Insight into Colorectal Carcinogenesis in Lynch Syndrome

Lynch syndrome is a hereditary cancer-predisposing syndrome caused by germline defects in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Carriers of pathogenic mutations in these genes have an increased lifetime risk of developing colorectal cancer (CRC) and other malignancies. Despite intensive surveillance, Lynch patients typically develop CRC after 10 years of follow-up, regardless of the screening interval. Recently, three different molecular models of colorectal carcinogenesis were identified in Lynch patients based on when MMR deficiency is acquired. In the first pathway, adenoma formation occurs in an MMR-proficient background, and carcinogenesis is characterized by APC and/or KRAS mutation and IGF2, NEUROG1, CDK2A, and/or CRABP1 hypermethylation. In the second pathway, deficiency in the MMR pathway is an early event arising in macroscopically normal gut surface before adenoma formation. In the third pathway, which is associated with mutations in CTNNB1 and/or TP53, the adenoma step is skipped, with fast and invasive tumor growth occurring in an MMR-deficient context. Here, we describe the association between molecular and histological features in these three routes of colorectal carcinogenesis in Lynch patients. The findings summarized in this review may guide the use of individualized surveillance guidelines based on a patient’s carcinogenesis subtype.

Immune-Mediated Myelopathies: A Review of Etiologies, Diagnostic Approach, and Therapeutic Management

Myelopathy is a broad term used to describe a heterogeneous group of disorders that affects the spinal cord; the focus of this article will be a subgroup of these disorders with an autoimmune and inflammatory-based pathology. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks, but sometimes can have a more insidious or subacute presentation, which can make the diagnosis more puzzling. Despite relatively low incidence rates, almost a third of affected patients are left with severely disabling symptoms. Prompt recognition of the underlying etiology is essential so that a specific targeted therapy can be implemented for optimal outcomes. The authors discuss a systematic approach to immune-mediated myelopathies, with a focus on the unique characteristics of each that may aid in diagnosis.

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients’ quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effect, but the genesis of chemotherapy-induced peripheral neuropathy is not linked to a single mechanism. This paper aims from one side at summarizing and explaining all the scattering mechanisms of chemotherapy-induced peripheral neuropathy through a detailed literature revision, on the other side at finding new approaches to possible treatments, in order to facilitate the collaboration between oncologists, hematologists and hospital pharmacists.

Pathogenesis and prevention of pressure ulcer

The number of pressure ulcer patients is increasing owing to the aging population and increased incidence of elderly illness. This review article aims to introduce the current knowledge on the pathogenesis and prevention of pressure ulcers. The development of a pressure ulcer is associated with external factors such as pressure, shear stress, and friction and internal factors such as age, general condition, skin condition, and nutritional status. Pressure ulcers typically develop over bone protrusions, which are most pressured by weight, but may also be caused by external pressure by medical devices or other objects applied to the patient. This tissue damage is caused by continuous deformation of the tissue due to the pressure acting perpendicular to the tissue surface and shear stress acting parallel to the tissue, either alone or in combination. Limitation of activity and mobility, skin condition, blood circulation and oxygen saturation, nutrition, humidity, body temperature, age, low pain sensitivity, blood count, and general and mental conditions are the primary risk factors for pressure ulcers. A mattress and cushion that reduce pressure and an appropriate posture are necessary to prevent pressure ulcers. In patients with urinary incontinence, contaminated skin should be washed with a mild detergent and absorbent pads and topical protective agents should be used to protect the skin from moisture. Sufficient nutrition may help prevent wounds in patients who are susceptible to pressure ulcers. Furthermore, early screening, individualized management of posture, and regular skin and nutrition monitoring are essential to prevent pressure ulcers.

Environmental patterns of brown moss- and Sphagnum-associated microbial communities

Northern peatlands typically develop through succession from fens dominated by the moss family Amblystegiaceae to bogs dominated by the moss genus Sphagnum. How the different plants and abiotic environmental conditions provided in Amblystegiaceae and Sphagnum peat shape the respective moss associated microbial communities is unknown. Through a large-scale molecular and biogeochemical study spanning Arctic, sub-Arctic and temperate regions we assessed how the endo- and epiphytic microbial communities of natural northern peatland mosses relate to peatland type (Sphagnum and Amblystegiaceae), location, moss taxa and abiotic environmental variables. Microbial diversity and community structure were distinctly different between Amblystegiaceae and Sphagnum peatlands, and within each of these two peatland types moss taxon explained the largest part of microbial community variation. Sphagnum and Amblystegiaceae shared few (< 1% of all operational taxonomic units (OTUs)) but strikingly abundant (up to 65% of relative abundance) OTUs. This core community overlapped by one third with the Sphagnum-specific core-community. Thus, the most abundant microorganisms in Sphagnum that are also found in all the Sphagnum plants studied, are the same OTUs as those few shared with Amblystegiaceae. Finally, we could confirm that these highly abundant OTUs were endophytes in Sphagnum, but epiphytes on Amblystegiaceae. We conclude that moss taxa and abiotic environmental variables associate with particular microbial communities. While moss taxon was the most influential parameter, hydrology, pH and temperature also had significant effects on the microbial communities. A small though highly abundant core community is shared between Sphagnum and Amblystegiaceae.