Demonstration and imaging of cryogenic magneto-thermoelectric cooling in a van der Waals semimetal.

Attaining viable thermoelectric cooling at cryogenic temperatures is of considerable fundamental and technological interest for electronics and quantum materials applications. In-device temperature control can provide more efficient and precise thermal environment management compared with conventional global cooling. The application of a current and perpendicular magnetic field gives rise to cooling by generating electron-hole pairs on one side of the sample and to heating due to their recombination on the opposite side, which is known as the Ettingshausen effect. Here we develop nanoscale cryogenic imaging of the magneto-thermoelectric effect and demonstrate absolute cooling and an Ettingshausen effect in exfoliated WTe2 Weyl semimetal flakes at liquid He temperatures. In contrast to bulk materials, the cooling is non-monotonic with respect to the magnetic field and device size. Our model of magneto-thermoelectricity in mesoscopic semimetal devices shows that the cooling efficiency and the induced temperature profiles are governed by the interplay between sample geometry, electron-hole recombination length, magnetic field, and flake and substrate heat conductivities. The observations open the way for the direct integration of microscopic thermoelectric cooling and for temperature landscape engineering in van der Waals devices.

Child bicyclist injuries: are we obtaining enough information in the emergency department chart?

OBJECTIVE: The purpose of this study was to assess the range of information relevant to bicyclist injury research that is available on routinely completed emergency department medical records. METHODS: A retrospective chart review of emergency department medical records was conducted on children who were injured as bicyclists and treated at an urban level I pediatric trauma center. A range of variables relevant to bicyclist injury research and prevention was developed and organized according to the Haddon matrix. Routinely completed free text emergency department medical records were assessed for the presence of each of the targeted elements. In addition, medical records of seriously injured patients (for whom a more structured medical record is routinely used) were compared to free form records of less seriously injured patients to identify differences in documentation that may be related to the structure of the medical record. RESULTS: Information related to previous medical history (96% of records), diagnosis (89%), documentation of pre-hospital care (82%), and child traumatic contact points (81%) were documented in the majority of medical records. Information relevant to prevention efforts was less commonly documented: identification of motor vehicle/object involved in crash (58%), the precipitating event (24%), the location of the crash (23%), and documentation of helmet use (23%). Records of seriously injured patients demonstrated significantly higher documentation rates for pre-hospital care and child traumatic contact points, and significantly lower documentation rates for previous medical history, child kinematics, main body parts impacted, and location of injury event. CONCLUSIONS: Routinely completed free text emergency department medical records contain limited information that could be used by injury researchers in effective surveillance. In particular information relating to the circumstances of the crash event that might be used to design or target prevention efforts is typically lacking. Routine use of more structured medical records has the potential to improve documentation of key information.

Serotype prevalence of occult pneumococcal bacteremia.

OBJECTIVE: The licensure and use of a pneumococcal conjugate vaccine that is immunogenic in children who are younger than 2 years may affect the epidemiology of occult bacteremia. This study was conducted to determine the serotype prevalence of Streptococcus pneumoniae isolates from children with occult bacteremia and to document the proportion that would be covered by the recently licensed heptavalent pneumococcal conjugate vaccine. METHODS: A cohort of 5901 children who were 2 to 24 months of age and had a temperature of >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department was studied to determine the prevalence of S pneumoniae serotypes. Patients were excluded if their immune system was suppressed, they had a diagnosis of a focal infection, they were evaluated by lumbar puncture, they were admitted to the hospital, or they died during initial evaluation. Blood cultures were inoculated into pediatric blood culture bottles and processed using an automated carbon dioxide monitoring system. All pneumococcal isolates were serotyped on the basis of capsular swelling with type-specific antisera (Quellung reaction). RESULTS: The study population consisted of 5901 patients. The overall rate of occult bacteremia was 1.9% (95% confidence interval [CI]: 1.5-2.3). S pneumoniae accounted for 92 of 111 isolates (82.9%; 95% CI: 74.6-89.4) in children with occult bacteremia. Eight pneumococcal serotypes were represented: 6A (2%), 9V (6%), 19F (6%), 18C (8%), 4 (9%), 6B (13%), 23F (15%), and 14 (42%). Serotypes 14, 6B, and 23F accounted for 69.3% (95% CI: 58.6-78.7) of typed isolates. In the cohort, 97.7% (95% CI: 92-99.7) of isolated serotypes are represented in the newly licensed heptavalent pneumococcal conjugate vaccine. The single isolated serotype that would not have been covered by the currently licensed heptavalent pneumococcal conjugate vaccine was 6A. CONCLUSIONS: S pneumoniae accounts for the vast majority of bacterial pathogens in children with occult bacteremia. As indicated by the results of this study, the heptavalent pneumococcal conjugate vaccine may prevent the majority of occult pneumococcal bacteremia episodes. The 2 cases of bacteremia with a serotype that would not have been included in the vaccine both were due to serotype 6A. It has been noted that there is potential nonvaccine serotype and subgroup cross-protection (6A from 6B) afforded to children who are immunized with the heptavalent vaccine. The high potential efficacy of the heptavalent pneumococcal conjugate vaccine for strains that cause occult bacteremia in our population may have a profound effect on the treatment of children with fever without a source. There has been an alarming and rapid emergence of antibiotic-resistant pneumococcal strains. Less pressure to use broad-spectrum antibiotics, which in turn causes further antibiotic resistance, should result. Laboratory testing and hospitalization also should be reduced. The prevalence rates determined by this study may be used as baseline data for comparison of serotype rates of occult pneumococcal bacteremia after widespread use of the heptavalent vaccine.

Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome.

OBJECTIVE: To evaluate selected characteristics of occult bacteremia in the post-Haemophilus influenzae type b (HIB) vaccine era. METHODS: A retrospective cohort study was performed involving 5901 children 2 to 24 months old with fever >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department (ED) between February 1993 and June 1996. Patients were excluded if immune-suppressed, diagnosed with a focal infection, evaluated by lumbar puncture, or admitted to the hospital during initial evaluation. Prevalence of occult bacteremia, distribution of current pathogenic organisms, and time to positive culture in a continuously monitored system were determined. All patients with cultures positive for pathogenic bacteria were reevaluated and serious adverse outcomes were documented. RESULTS: The prevalence of occult bacteremia was 1.9% (95% confidence interval: 1.5%-2.3%). Streptococcus pneumoniae accounted for 82.9% of all pathogens and H influenzae was not a causative organism in this cohort. The mean time to positive culture was significantly shorter for pathogens compared with contaminants (14.9 hours vs 31.1 hours). A culture that was positive in

Who can give a pediatric trauma history for children injured in bicycle crashes?

Emergency Departments are important sites for injury surveillance but the quality of data collected has not been evaluated. This prospective cohort study assessed the ability of various respondents to provide circumstantial information following pediatric bicyclist trauma. A semi-structured survey tool was administered in the Emergency Department of a Level One Pediatric Trauma Center for 448 child bicyclists. The injured child provided more complete information when compared to witnesses and Emergency Medical Services personnel. No one respondent type provided the complete history. To obtain thorough injury circumstantial information, multiple respondents should be interviewed utilizing a semi-structured questionnaire.

Does adult fracture repair recapitulate embryonic skeletal formation?

Bone formation is a continuous process that begins during fetal development and persists throughout life as a remodeling process. In the event of injury, bones heal by generating new bone rather than scar tissue; thus, it can accurately be described as a regenerative process. To elucidate the extent to which fetal skeletal development and skeletal regeneration are similar, we performed a series of detailed expression analyses using a number of genes that regulate key stages of endochondral ossification. They included genes in the indian hedgehog (ihh) and core binding factor 1 (cbfa1) pathways, and genes associated with extracellular matrix remodeling and vascular invasion including vascular endothelial growth factor (VEGF) and matrix metalloproteinase 13 (mmp13). Our analyses suggested that even at the earliest stages of mesenchymal cell condensation, chondrocyte (ihh, cbfa1 and collagen type II-positive) and perichondrial (gli1 and osteocalcin-positive) cell populations were already specified. As chondrocytes matured, they continued to express cbfa1 and ihh whereas cbfa1, osteocalcin and gli1 persisted in presumptive periosteal cells. Later, VEGF and mmp13 transcripts were abundant in chondrocytes as they underwent hypertrophy and terminal differentiation. Based on these expression patterns and available genetic data, we propose a model where Ihh and Cbfa1, together with Gli1 and Osteocalcin participate in establishing reciprocal signal site of injury. The persistence of cbfa1 and ihh, and their targets osteocalcin and gli1, in the callus suggests comparable processes of chondrocyte maturation and specification of a neo-perichondrium occur following injury. VEGF and mmp13 are expressed during the later stages of healing, coincident with the onset of vascularization of the callus and subsequent ossification. Taken together, these data suggest the genetic mechanisms regulating fetal skeletogenesis also regulate adult skeletal regeneration, and point to important regulators of angiogenesis and ossification in bone regeneration.

Common molecular pathways in skeletal morphogenesis and repair.

The formation of bone is a continual process in vertebrate development, initiated during fetal development and persisting in adulthood in the form of remodeling and repair. The remarkable capacity of skeletal tissues to regenerate has led to the hypothesis that the molecular signaling pathways regulating skeletogenesis are shared during fetal development and adult wound healing. A number of key regulatory pathways that are required for endochondral ossification during fetal development are described, and their reintroduction in fracture repair demonstrated. Secreted proteins such as Sonic and Indian hedgehog exert their effect on pattern formation and chondrogenesis in the appendicular skeleton, partly through regulation of molecules such as bone morphogenic proteins (Bmps) and parathyroid hormone-related peptide (PTHrP). Once chondrocytes have matured and hypertrophied, they undergo apoptosis and are replaced by bone; the transcription factor Cbfal plays a critical role in this process of chondrocyte differentiation and ossification. Analyses of the expression patterns of these genes during fracture healing strongly suggest that they play equivalent roles in adult wound repair. Knowledge acquired through the study of fetal skeletogenesis will undoubtedly contribute to an understanding of fracture repair, and subsequently guide the development of biologically based therapeutic interventions.

Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy1.1lo Lin-/lo Sca-1+) that contain > 2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [3H]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in G0/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in G0/G1. The injection of 100 G0/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donor-derived multilineage reconstitution of the peripheral blood was observed in recipients of 100 G0/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity.

Heterogeneity of hematopoietic stem cells.

Hematopoietic stem cells are capable of multi-lineage differentiation to all blood cell types as well as self-renewal and radioprotection. Thy-1.1lo Lin-/lo Sca-1+ cells are a heterogeneous mixture of quiescent and self-renewing hematopoietic stem cells as well as multi-lineage expanding cells.

Steel factor influences the distribution and activity of murine hematopoietic stem cells in vivo.

To determine the effects of steel factor (SIF) on the number and distribution of phenotypically defined hematopoietic stem cells in vivo, mice were treated with continuous s.c. infusions of SIF for up to 7 days. The bone marrow demonstrated a transient 5-fold increase in the number of c-kit-positive lineage-negative/low cells with no change in cellularity. The radioprotective capacity of bone marrow cells was significantly reduced, and a 30% decrease in Thylo Lin-/lo Sca-1+ stem cells (Sca+ cells) was observed. In marked contrast, in the spleen a 2-fold increase in cellularity was accompanied by a 24-fold increase in c-kit-positive lineage-negative/low cells. SIF-treated spleen cells provided increased radioprotection and a corresponding 4-fold increase in the number of Sca+ cells. In the peripheral blood, an increase in both neutrophils and lymphocytes resulted; however, the number of c-kit-positive lineage-negative/low cells remained < 1%. SIF produced a 25-fold increase in radioprotection capacity and a 20-fold increase in the number of Sca+ cells in the peripheral blood. The increased radioprotection capacity of both the spleen cells and peripheral blood cells was associated with donor-derived, long-term multilineage reconstitution of recipient mice. The total number of Sca+ cells isolated per mouse after SIF treatment was not significantly increased. These results show that exogenous SIF treatment causes a redistribution of Sca+ cells and stem cell activity while having little effect on the total number of stem cells in the mouse.