A new type of carbon resistance thermometer with excellent thermal contact at millikelvin temperatures

Using a new brand of commercially available carbon resistor we built a cryogenic thermometer with an extremely good thermal contact to its thermal environment. Because of its superior thermal contact the thermometer is insensitive to low levels of spurious radio frequency heating. We calibrated our thermometer down to 5mK using a quartz tuning fork He-3 viscometer and measured its thermal resistance and thermal response time.Comment: 5 pages, 4 figure

Scaling predictions for radii of weakly bound triatomic molecules

The mean-square radii of the molecules $^4$He$_3$, $^4$He$_2-^6$Li, $^4$He$_2-^7$Li and $^4$He$_2-^{23}$Na are calculated using a three-body model with contact interactions. They are obtained from a universal scaling function calculated within a renormalized scheme for three particles interacting through pairwise Dirac-delta interaction. The root-mean-square distance between two atoms of mass $m_A$ in a triatomic molecule are estimated to be of de order of ${\cal C}\sqrt{\hbar^2/[m_A(E_3-E_2)]}$, where $E_2$ is the dimer and $E_3$ the trimer binding energies, and ${\cal C}$ is a constant (varying from $\sim 0.6$ to $\sim 1$) that depends on the ratio between $E_2$ and $E_3$. Considering previous estimates for the trimer energies, we also predict the sizes of Rubidium and Sodium trimers in atomic traps.Comment: 7 pages, 2 figure

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Super-resolution Microscopy Reveals Photoreceptor-Specific Subciliary Location and Function of Ciliopathy-Associated Protein CEP290

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout the length of the CC whereas it is confined to the very base of primary cilia in human retinal pigment epithelium-1 cells. We found Y-shaped links, ciliary substructures between microtubules and membrane, throughout the length of the CC. Severe CEP290 deficiencies in mouse models did not prevent assembly of cilia or cause obvious mislocalization of ciliary components in early stages of degeneration. There were fewer cilia and no normal outer segments in the mutants, but the Y-shaped links were clearly present. These results point to photoreceptor-specific functions of CEP290 essential for CC maturation and stability following the earliest stages of ciliogenesis

Abundance And Vertical Flux Of Pseudo-Nitzschia In The Northern Gulf Of Mexico

Many species of the ubiquitous pennate diatom genus Pseudo-nitzschia have recently been discovered to produce domoic acid, a potent neurotoxin which causes Amnesic Shellfish Poisoning (ASP). Pseudo-nitzschia spp. were extremely abundant (up to 10(8) cells l(-1); present in 67% of 2195 samples) from 1990 to 1994 on the Louisiana and Texas, USA, continental shelves and moderately abundant (up to 10(5) cells l(-1); present in 18% of 192 samples) over oyster beds in the Terrebonne Bay estuary in Louisiana in 1993 and 1994. On the shelf there was a strong seasonal cycle with maxima every spring for 5 yr and sometimes in the fall, which were probably related to river flow, water column stability, and nutrient availability. In contrast, in the estuary there was no apparent seasonal cycle in abundance, but the time series of data is relatively short and the environment highly variable. At one site on the shelf, where sediment traps were deployed from spring to fall and sampled at frequent intervals in both 1990 and 1991, approximately 50% of the Pseudo-nitzschia spp. cells present in the water sank into sediment traps. Pseudo-nitzschia spp. were also abundant in surficial sediments. The species of Pseudo-nitzschia present, during this study were not routinely identified with the methods employed. However, toxin-producing P. multiseries has been identified previously from Galveston Bay, Texas, and cells from a bloom on the shelf in June 1993 were identified by scanning electron microscopy as P. pseudodelicatissima, which is sometimes toxic. Although there have been no known outbreaks of ASP in this area, historical data suggests that Pseudo-nitzschia spp,abundance may have increased on the shelf since the 1950s. It is hypothesized that the increase is due to doubling of the nutrient loading from the Mississippi and Atchafalaya rivers and increased eutrophication on the shelf

Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons

The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the expression of these unique combinations of genes is unknown for any class of cortical neuron. Here, we report that Fezf2 is a selector gene able to regulate the expression of gene sets that collectively define mouse corticospinal motor neurons (CSMN). We find that Fezf2 directly induces the glutamatergic identity of CSMN via activation of Vglut1 (Slc17a7) and inhibits a GABAergic fate by repressing transcription of Gad1. In addition, we identify the axon guidance receptor EphB1 as a target of Fezf2 necessary to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype–specific and pan-neuronal gene batteries by a single transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity

Secondary Bacterial Pneumonias and Bloodstream Infections in Patients Hospitalized with COVID-19

Group Name: The Emory COVID-19 Quality and Clinical Research Collaborative Background: Patients hospitalized with COVID-19 are at risk of secondary infections—10%–33% develop bacterial pneumonia and 2%–6% develop bloodstream infection (BSI). We conducted a retrospective cohort study to identify the prevalence, microbiology, and outcomes of secondary pneumonias and BSIs in patients hospitalized with COVID-19. Methods: Patients aged ≥18 years with a positive SARS-CoV-2 real-time polymerase chain reaction assay admitted to 4 academic hospitals in Atlanta, Georgia, between February 15 and May 16, 2020, were included. We extracted electronic medical record data through June 16, 2020. Microbiology tests were performed according to standard protocols. Possible ventilator-associated pneumonia (PVAP) was defined according to Centers for Disease Control and Prevention (CDC) criteria. We assessed in-hospital mortality, comparing patients with and without infections using the χ(2) test. SAS University Edition software was used for data analyses. Results: In total, 774 patients were included (median age, 62 years; 49.7% female; 66.6% black). In total, 335 patients (43.3%) required intensive care unit (ICU) admission, 238 (30.7%) required mechanical ventilation, and 120 (15.5%) died. Among 238 intubated patients, 65 (27.3%) had a positive respiratory culture, including 15 with multiple potential pathogens, for a total of 84 potential pathogens. The most common organisms were Staphylococcus aureus (29 of 84; 34.5%), Pseudomonas aeruginosa (16 of 84; 19.0%), and Klebsiella spp (14 of 84; 16.7%). Mortality did not differ between intubated patients with and without a positive respiratory culture (41.5% vs 35.3%; P = .37). Also, 5 patients (2.1%) had a CDC-defined PVAP (1.7 PVAPs per 1,000 ventilator days); none of them died. Among 536 (69.3%) nonintubated patients, 2 (0.4%) had a positive Legionella urine antigen and 1 had a positive respiratory culture (for S. aureus). Of 774 patients, 36 (4.7%) had BSI, including 5 with polymicrobial BSI (42 isolates total). Most BSIs (24 of 36; 66.7%) had ICU onset. The most common organisms were S. aureus (7 of 42; 16.7%), Candida spp (7 of 42; 16.7%), and coagulase-negative staphylococci (5 of 42; 11.9%); 12 (28.6%) were gram-negative. The most common source was central-line–associated BSI (17 of 36; 47.2%), followed by skin (6 of 36; 16.7%), lungs (5 of 36; 13.9%), and urine (4 of 36; 11.1%). Mortality was 50% in patients with BSI versus 13.8% without (p < 0.0001). Conclusions: In a large cohort of patients hospitalized with COVID-19, secondary infections were rare: 2% bacterial pneumonia and 5% BSI. The risk factors for these infections (intubation and central lines, respectively) and causative pathogens reflect healthcare delivery and not a COVID-19–specific effect. Clinicians should adhere to standard best practices for preventing and empirically treating secondary infections in patients hospitalized with COVID-19. Funding: No Disclosures: Non

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

ABSTRACT Despite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oral M. tuberculosis vaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4 + T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can develop vaccine-induced SIV-specific IgA and IgG antibodies and cellular immune responses within weeks of life. Our data further suggest that affinity maturation of vaccine-induced plasma antibodies and induction of mucosal IgA responses at potential SIV entry sites are associated with better control of viral replication, thereby likely reducing SIV morbidity. IMPORTANCE Despite significant progress in reducing peripartum MTCT of HIV with ART, continued access to ART throughout the breastfeeding period is still a limiting factor. Breast milk exposure to HIV accounts for up to 44% of MTCT. Alternative measures, in addition to ART, are needed to achieve the goal of an AIDS-free generation. Pediatric HIV vaccines constitute a core component of such efforts. The results of our pediatric vaccine study highlight the potential importance of vaccine-elicited mucosal Env-specific IgA responses in combination with high-avidity systemic Env-specific IgG in protection against oral SIV transmission and control of viral replication in infant macaques. The induction of potent mucosal IgA antibodies by our vaccine is remarkable considering the age-dependent development of mucosal IgA responses postbirth. A deeper understanding of postnatal immune development may inform the design of improved vaccine strategies to enhance systemic and mucosal SIV/HIV antibody responses

Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA). OBJECTIVES: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives. METHODS: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups. RESULTS: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values \u3c 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021). CONCLUSIONS: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum

Diagnosis and management of functional tic-like phenomena

Over the past 3 years, a global phenomenon has emerged characterized by the sudden onset and frequently rapid escalation of tics and tic-like movements and phonations. These symptoms have occurred not only in youth known to have tics or Tourette syndrome (TS), but also, and more notably, in youth with no prior history of tics. The Tourette Association of America (TAA) convened an international, multidisciplinary working group to better understand this apparent presentation of functional neurological disorder (FND) and its relationship to TS. Here, we review and summarize the literature relevant to distinguish the two, with recommendations to clinicians for diagnosis and management. Finally, we highlight areas for future emphasis and research