First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

A data resource from concurrent intracranial stimulation and functional MRI of the human brain.

Mapping the causal effects of one brain region on another is a challenging problem in neuroscience that we approached through invasive direct manipulation of brain function together with concurrent whole-brain measurement of the effects produced. Here we establish a unique resource and present data from 26 human patients who underwent electrical stimulation during functional magnetic resonance imaging (es-fMRI). The patients had medically refractory epilepsy requiring surgically implanted intracranial electrodes in cortical and subcortical locations. One or multiple contacts on these electrodes were stimulated while simultaneously recording BOLD-fMRI activity in a block design. Multiple runs exist for patients with different stimulation sites. We describe the resource, data collection process, preprocessing using the fMRIPrep analysis pipeline and management of artifacts, and provide end-user analyses to visualize distal brain activation produced by site-specific electrical stimulation. The data are organized according to the brain imaging data structure (BIDS) specification, and are available for analysis or future dataset contributions on openneuro.org including both raw and preprocessed data.

Bronchovascular responses to intravenous contrast media for helical CT pulmonary angiography.

CT angiography is now commonly used for the diagnosis of pulmonary embolism, but the contrast media used for imaging produces various hemodynamic changes. In this study, we investigated the bronchovascular and hemodynamic responses to intravenous iopromide, a non-ionic contrast agent used for pulmonary CT angiograms, in anesthetized, mechanically ventilated sheep (n = 6). Bronchial blood flow and cardiac output were measured with ultrasonic flow probes. Systemic and pulmonary arterial pressures were continuously monitored. Injections of 0.9% NaCl (120 ml over 30 s) or iopromide (300 mg/ml, 120 ml over 30 s) were given in random order in a peripheral vein with an angiogram infuser and hemodynamic changes were determined. After these parameters returned to baseline, the left pulmonary artery (LPA) was occluded with a snare and the animals were allowed to stabilize. Injections of NaCl and iopromide were repeated in random order as before. There were no significant hemodynamic effects with infusion of NaCl. With intact pulmonary vasculature, NaCl and iopromide did not cause significant changes in arterial blood gases, however, cardiac output (QT, L/min), mean systemic and pulmonary arterial pressures (PSA and PPA, Torr) increased and bronchovascular resistance (BVR, Torr x min/ml), decreased. Following LPA ligation, pH and PO2 significantly decreased over baseline, whereas PCO2 increased. After LPA ligation, iopromide produced a greater decrease in BVR as compared with preligation intact pulmonary vasculature. In conclusion, iopromide caused rapid hemodynamic changes and decreased BVR, likely secondary to osmolar stress. Bronchovascular effects were more pronounced after pulmonary arterial occlusion.

Controlled trial of inhaled fluticasone propionate in moderate to severe COPD.

Inhaled corticosteroids are often used in the treatment of stable chronic obstructive pulmonary disease (COPD), however, studies of these agents have had mixed results. Previous trials have often excluded subjects with bronchodilator response, have failed to evaluate effect on gas exchange, and have usually looked at only post- rather than prebronchodilator forced expiratory volume (FEV). Our objective was to better assess the efficacy of topical corticosteroids in the treatment of COPD. We used a prospective, randomized, double-blinded, placebo-controlled, crossover study at the Outpatient Department, Department of Veterans Affairs Medical Center. Thirty-six COPD patients with a mean (+/- SD) FEV1 of 1.10 +/- 0.43 L, with or without significant bronchodilator response participated in the study. Subjects received a 3-month course of inhaled fluticasone propionate (220 micro g/puff) or identical-appearing placebo by metered-dose inhaler at 2 puffs twice daily, followed by crossover to the alternative inhaler for an additional 3 months. Fluticasone treatment resulted in a higher prebronchodilator FEV1 (1.17 +/- 0.08 L [mean +/- SEM] versus 1.07 +/- 0.08 L, p = 0.001), a higher PaO2 (66.6 +/- 1.4 mmHg versus 63.6 +/- 1.6 mmHg, p = 0.002), and a better dyspnea score on the chronic respiratory questionnaire (3.70 +/- 0.18 versus 3.47 +/- 0.19, p = 0.03). A trend towards fewer exacerbations with fluticasone did not quite meet statistical significance (p = 0.11). Inhaled fluticasone over 3 months improved prebronchodilator airflow obstruction and oxygenation while decreasing dyspnea in moderate to severe COPD. Postbronchodilator FEV1 was not significantly changed.

Ulnar collateral ligament reconstruction in athletes: muscle-splitting approach without transposition of the ulnar nerve.

Eighty-three athletes with medial elbow instability underwent reconstruction of the anterior band of the ulnar collateral ligament with a muscle-splitting approach without transposition of the ulnar nerve. The purposes of this study were to describe postoperative neurologic outcomes in all 83 athletes and to describe the 2-year follow-up in 33 athletes. Postoperatively, 5% of this group had transient ulnar nerve symptoms, all of which resolved with nonoperative management. There were no reoperations for nerve dysfunction and no permanent nerve problems. At 2- to 4-year follow-ups, 93% of the highly competitive athletes who had not had a prior surgical procedure had an excellent result. All athletes, regardless of whether they had a prior procedure, were able to return to their sport. These surgical modifications to the ulnar collateral ligament reconstruction yielded a decreased postoperative complication rate and improved outcomes compared with the results of prior procedures.

Effect of expiratory resistive loading on the noninvasive tension-time index in COPD.

Expiratory resistive loading (ERL) is used by chronic obstructive pulmonary disease (COPD) patients to improve respiratory function. We, therefore, used a noninvasive tension-time index of the inspiratory muscles (TT(mus) = I/PI(max) x TI/TT, where I is mean inspiratory pressure estimated from the mouth occlusion pressure, PI(max) is maximal inspiratory pressure, TI is inspiratory time, and TT is total respiratory cycle time) to better define the effect of ERL on COPD patients. To accomplish this, we measured airway pressures, mouth occlusion pressure, respiratory cycle flow rates, and functional residual capacity (FRC) in 14 COPD patients and 10 normal subjects with and without the application of ERL. TT(mus) was then calculated and found to drop in both COPD and normal subjects (P<0.05). The decline in TT(mus) in both groups resulted solely from a prolongation of expiratory time with ERL (P<0.001 for COPD, P<0.05 for normal subjects). In contrast to the COPD patients, normal subjects had an elevation in I and FRC, thus minimizing the decline in TT(mus). In conclusion, ERL reduces the potential for inspiratory muscle fatigue in COPD by reducing TI/TT without affecting FRC and I.

Comparative effects of alpha-receptor stimulation and nitrergic inhibition on bronchovascular tone.

Adrenergic agonists are known to influence bronchial blood flow and bronchovascular resistance. Recently, the nitrergic system has also been implicated in the control of bronchovascular tone. In this study, we compared the effects of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the alpha(1)-receptor agonist phenylephrine on bronchovascular resistance in anesthetized sheep (n = 9). Bronchial blood flow, cardiac output, and systemic and pulmonary arterial pressures were continuously monitored. Phenylephrine (1.2-3.4 microg. kg(-1). min(-1)) was infused intravenously to increase mean systemic arterial pressure above 95 Torr for 10 min and then was discontinued. When hemodynamic parameters returned to baseline, nebulized phenylephrine (10 mg) was given over 10 min. When parameters again normalized, L-NAME (30 mg/kg) was infused intravenously over 1 min. Intravenous phenylephrine increased systemic vascular resistance by 40% at 10 min with no concurrent increase in bronchovascular resistance, but inhaled phenylephrine increased bronchovascular resistance by 66% at 10 min. By comparison, intravenous L-NAME produced a rapid and sustained fivefold increase in bronchovascular resistance at 10 min. We conclude that, although alpha-agonist stimulation has some influence on bronchovascular resistance in sheep, the nitrergic system has predominant control of bronchovascular tone.

La Crosse and other forms of California encephalitis.

The California serogroup viruses are mosquito viruses that cause human infections on five continents. They are maintained and amplified in nature by a wide variety of mosquito vectors and mammalian hosts; they thrive in a remarkably wide variety of microclimates (eg, tropical, coastal temperate marshland, lowland river valleys, alpine valleys and highlands, high boreal deserts, and arctic steppes). In 1993, California serogroup viruses caused 71% of all cases of arboviral illness in the United States, principally La Crosse encephalitis. The 30 to 180 annual cases of La Crosse encephalitis represent 8% to 30% of all cases of encephalitis, rendering this illness the most common and important endemic mosquito-borne illness in the USA. Subclinical or mild infections are much more common. Methods and results acquired from intense study of California serogroup viruses have been applied, with benefit, to the study of the ecology and pathogenesis of many more serious human arboviral illnesses. The evolutionary potential of viruses, with particular reference to the development of more virulent strains, has been studied more closely in the California serogroup viruses than in almost any other agent of human disease.

Characterization of La Crosse virus RNA in autopsied central nervous system tissues.

A reverse transcription-PCR (RT-PCR) technique was used to detect La Crosse (LAC) virus RNA in the central nervous system (CNS) tissues of two patients who died of LAC encephalitis in 1960 and 1978. Viral RNA was readily detected by RT-PCR although the tissues had been stored frozen for up to 37 years. LAC virus was detected in the cerebral cortex but not in other CNS tissues. RT-PCR allowed detection of replicative forms of the virus, indicating that the virus was actively replicating in the specific CNS tissues. The small (S) RNA segments of the viruses from the CNS samples were demonstrated to be genetically similar by single-strand conformation polymorphism analyses. These S RNA segments were then sequenced; only two base changes were demonstrated between the 1960 and the 1978 samples, suggesting that LAC virus is genetically stable in areas of endemicity. The RT-PCR analyses of analyte directly from CNS tissues allows study of the virus without passage in cell culture.

Effect of aerosolized acetylcholine on bronchial blood flow.

We studied the effects of aerosolized as well as intravenous infusion of acetylcholine on bronchial blood flow in six anesthetized sheep. Intravenous infusion of acetylcholine, at a dose of 2 microg/kg, increased bronchial blood flow from 45 +/- 15 (SE) to 74 +/- 30 ml/min, and vascular conductance increased by 76 +/- 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 microg/kg decreased bronchial vascular conductance by approximately 10%. At an aerosolized dose of 200 microg/kg, the bronchial vascular conductance increased by approximately 15%, and there was no further increase in conductance when the aerosolized dose was increased to 2,000 microg/kg. Pretreatment of animals with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester hydrochloride, partially blocked the vasodilatory effects of intravenous acetylcholine and completely blocked the vasodilatory effects of high-dose aerosolized acetylcholine. These data suggest that aerosolized acetylcholine does not readily penetrate the vascular wall of bronchial circulatory system and, therefore, has minimal vasodilatory effects on the bronchial vasculature.

Evidence that fatal human infections with La Crosse virus may be associated with a narrow range of genotypes.

La Crosse (LAC) virus belongs to the California (CAL) serogroup of the genus Bunyavirus, family Bunyaviridae. It is considered one of the most important mosquito-borne pathogens in North America, especially in the upper Mid-West, where it is associated with encephalitis during the time of year when mosquitoes are active. Infections occur most frequently in children and young adults and, while most cases are resolved after a period of intense illness, a small fraction (< 1%) are fatal. At present there have only been three isolates of LAC virus from humans all made from brain tissue postmortem. The cases yielding viruses are separated chronologically by 33 years and geographically from Minnesota/Wisconsin (1960, 1978) to Missouri (1993). The M RNA sequence of the first two isolates was previously reported. The present study extends the observations to the isolate from the 1993 case and includes several mosquito isolates as well. A comparison of the M RNAs of these viruses shows that for the human isolates both nucleotide sequence and the deduced amino-acid sequence of the encoded proteins are highly conserved, showing a maximum variation of only 0.91% and 0.69%, respectively. This high degree of conservation over time and space leads to the hypothesis that human infections with this particular genotype of LAC virus are those most likely to have a fatal outcome. It is also shown that a virus with this genotype could be found circulating in mosquitoes in an area more or less intermediate between the locations of the first and second fatal cases.

Management of bronchopleural fistula with a variable-resistance valve and a single ventilator.

Independent lung ventilation with two ventilators is sometimes used in the management of bronchopleural fistula (BPF). We describe a patient in whom gas flow through a large BPF was initially reduced, and subsequently eliminated, during differential lung ventilation using a single ventilator and a variable-resistance valve attached to one lumen of a bifurcated endotracheal tube.

Nitric oxide and beta-adrenergic agonist-induced bronchial arterial vasodilation.

In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 x 10(-2) M concentration). NO and isoetharine increased Qbr from 26.5 +/- 6.5 to 39.1 (SE) +/- 10.6 and 39.7 +/- 10.7 ml/min, respectively (n = 5). Administration of NO immediately after isoetharine further increased Qbr to 57.3 +/- 15.1 ml/min. NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 30 mg/kg, in 20 ml saline given i.v.) decreased Qbr to 14.6 +/- 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Qbr from 14.6 +/- 2.6 to 74.3 +/- 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, after L-NAME three sequential doses of isoetharine increased Qbr from 10.2 +/- 3.4 to 11.5 +/- 5.7, 11.7 +/- 4.7, and 13.3 +/- 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Qbr increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation, there seems to be a close interaction between adenosine 3',5'-cyclic monophosphate- and guanosine 3',5'-cyclic monophosphate-mediated vasodilation.

Controlled trial of oral prednisone in outpatients with acute COPD exacerbation.

Corticosteroids are often used in the outpatient treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD). To date, there are few data documenting the benefit of this practice. The objective of this randomized, double-blind, placebo-controlled trial was to assess the efficacy of corticosteroids in the outpatient treatment of COPD exacerbations. Twenty-seven patients presenting with acute COPD exacerbation were studied. In addition to continuing their previous medications and increasing their use of beta-agonists, patients were randomized to receive a 9-d tapering dose of either oral prednisone or placebo. Treatment with prednisone rather than placebo resulted in a more rapid improvement in arterial PO2 (PaO2) (1.12 mm Hg/d versus -0.03 mm Hg/day; p = 0.002), alveolar-arterial oxygen gradient (A-aDO2) (-1.16 mm Hg/d versus -0.03 mm Hg/day; p = 0.04), FEV1 (0.05 L/d versus 0.00 L/d; p = 0.006), and peak expiratory flow (PEF) (0.15 L/s/d versus 0.04 L/s/d; p = 0.009). Prednisone also resulted in fewer treatment failures (p = 0.002) and in a trend toward more rapid improvement in dyspnea scale scores. Outpatient treatment of acute COPD exacerbation with prednisone accelerates recovery of PaO2, A-aDO2, FEV1, and PEF, reduces the treatment failure rate, and improves subjective dyspnea.

Comparison of the M RNA genome segments of two human isolates of La Crosse virus.

The M genomic RNA segments of La Crosse (LAC) virus isolates from the brains of two children autopsied 18 years apart in Wisconsin were molecularly cloned using a reverse transcriptase-PCR assay and the nucleotide sequences of the cDNAs determined. The M RNA of each virus contains 4526 nucleotides, similar to that reported previously for a New York mosquito isolate of LAC. There were 20 nucleotide differences between the two human isolates, which results in the prediction of 7 amino acid changes in the proteins encoded in the single, long open reading frame of the M segment. One of these predicted differences occurs in the G2 glycoprotein and six in the G1 glycoprotein. The two viruses were identical in terms of predicted amino acid sequence in the region believed to represent a nonstructural protein. These data have been further compared to those available for two other California serogroup isolates.

Determining the rotational alignment of the femoral component in total knee arthroplasty using the epicondylar axis.

The posterior condylar surfaces of the femur are routinely used as the reference for the rotational orientation of the femoral component during most primary total knee arthroplasties. The purpose of this investigation was to identify a clearly discernible, reproducible secondary anatomic axis useful for determining the rotational orientation of the femoral component when the posterior condylar surfaces cannot be used. Seventy-five embalmed anatomic specimen femurs were studied. A surgical epicondylar axis was defined as the line connecting the lateral epicondylar prominence and the medial sulcus of the medial epicondyle. The posterior condylar angle was measured as the angle between the posterior condylar surfaces and the surgical epicondylar axis. Measurement of the posterior condylar angle referenced from the surgical epicondylar axis yielded a mean posterior condylar angle of 3.5 degrees (+/- 1.2 degrees) of internal rotation for males and a mean posterior condylar angle of 0.3 degree (+/- 1.2 degrees) of internal rotation for females. Thus, rotational alignment of the femoral component can be accurately estimated using the posterior condylar angle. The posterior condylar angle, referenced from the surgical epicondylar axis, provides a visual rotational alignment check during primary arthroplasty and may improve alignment of the femoral component at revision.

Ingrowth and formation of bone in defects in an uncemented fiber-metal total hip-replacement model in dogs.

An osseous defect was created in the acetabulum and femur of twenty dogs, and then a fiber-metal total hip prosthesis was inserted. A comparison was made between the effects of leaving the defects unfilled, filling the defects with an autogenous bone graft, and filling them with a 50:50 mixture of autogenous bone graft and a biphasic ceramic composed of hydroxyapatite and tricalcium phosphate. The characteristics of formation of bone within the sites of the defects and the extent of the ingrowth of bone into the underlying porous surface were analyzed. At six and twelve weeks after implantation, the dogs in the control group (unfilled defects) had the least amount of bone in the sites of the defects. In the dogs that had had an autogenous bone graft and those in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic, there were excellent osteoconductive properties in the filling of the sites of the defects with new bone. A comparison was made between the amount of bone that formed in the osseous defects and the amount that formed in the spaces of the porous-surfaced fiber-metal components of the prostheses, directly underlying and adjacent to the defects. At six weeks, the greatest amount of ingrowth of bone into the spaces of the underlying titanium fiber-metal acetabular components was seen in the control group (22 per cent of the porous surface), followed by the group in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic (19 per cent). The defects that had been filled only with autogenous bone graft had poor ingrowth of bone into the porous surface (4 per cent) and predominantly fibrous ingrowth. At twelve weeks, these defects again showed the least amount of ingrowth of bone (15 per cent) compared with the defects in the control group (24 per cent) and those that had been filled with a mixture of autogenous bone graft and biphasic ceramic (24 per cent). No statistically significant differences were found in the amount of ingrowth of bone into the defects that had been created in the femur in the three groups of dogs at either six or twelve weeks. However, the trends appeared to correlate with the data for the acetabular defects.

Lower rates of oral transmission of La Crosse virus by Aedes triseriatus venereally exposed after engorgement on immune chipmunks.

Transmission rates of La Crosse (LAC) virus observed in Aedes triseriatus females that had engorged on chipmunks with antibody to LAC and had been mated by infected males 5-11 days later (24%, 69/288) were 40% lower than in those fed on chipmunks without antibody (38%, 112/293). Similar results were obtained in three separate trials using males infected 1) by inoculation with prototype LAC virus, 2) transovarially with a field strain, or 3) transovarially with the field strain following passage through a viremic chipmunk. Similar rates were also observed in trials with F2 and F3 progeny of several strains of Ae. triseriatus collected from LAC-endemic and non-endemic areas. Reduction of oral transmission by venereally infected females mated by transovarially infected males following engorgement of antibody in chipmunks or other vertebrates could be important in the natural control of LAC virus, since most adult chipmunks sampled in endemic areas have antibodies neutralizing LAC. Ten-fold higher rates of venereal infection found in females mated by infected males 5 or more days after engorgement on LAC antibody-negative chipmunks than in those mated without prior engorgement extend previous findings of higher rates of transmission after engorgement on laboratory mice to include the natural vertebrate host.

Quantitation of La Crosse virus in venereally infected Aedes triseriatus.

The replication of two strains of La Crosse (LAC) virus, prototype and an unpassaged field isolate, was followed in intrathoracically inoculated male and venereally infected female Aedes triseriatus mosquitoes. The venereal infection rate following induced mating was 13.6% of 44 females inseminated by males inoculated with prototype virus, and 26.3% of 38 females inseminated by males inoculated with an unpassaged field strain. The males consistently contained concentrations of virus in reproductive tracts equal to or greater than those in salivary glands (SG). In contrast, venereally infected females generally contained the highest concentrations of virus in SG. Prototype LAC virus was demonstrable in nearly all organs of the infected females by 10 days following mating; the unpassaged field strain was detectable in all organ systems tested by day 6. There appeared to be no significant differences in replication between the prototype and field isolate viruses.