Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Sexually dimorphic differences in angiogenesis markers predict brain aging trajectories.

Aberrant angiogenesis could contribute to cognitive impairment, representing a therapeutic target for preventing dementia. However, most angiogenesis studies focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in two deeply phenotyped human cohorts (n=435, age 74 + 9) with longitudinal cognitive assessments, biospecimens, structural brain imaging, and clinical data. Machine learning and traditional statistics revealed sex dimorphic associations of plasma angiogenic growth factors with brain aging outcomes. Specifically, angiogenesis is associated with higher executive function and less brain atrophy in younger women (not men), a directionality of association that reverses around age 75. Higher levels of basic fibroblast growth factor, known for pleiotropic effects on multiple cell types, predicted favorable cognitive trajectories. This work demonstrates the relevance of angiogenesis to brain aging with important therapeutic implications for vascular cognitive impairment and dementia.

Sub-organism (acetylcholinesterase activity), population (survival) and chemical concentration responses reinforce mechanisms of antagonism associated with malathion toxicity.

Within human modified ecosystems the effects of individual stressors are difficult to establish amid co-occurring biological processes, environmental gradients and other stressors. Coupled examination of several endpoints across different levels of organisation may help elucidate the individual and combined effects of stressors and interactions. Malathion is a commonly used organophosphate pesticide that contaminates freshwaters and has strong negative effects on aquatic biota. However, both other stressors (e.g. increased sediment) and common ecosystem components (e.g. macrophytes and variable pH) can reduce the aqueous concentrations of malathion, reducing its toxic effects. We conducted a fully orthogonal bioassay to examine how pH (at 7 and 7.8) and sorptive processes (across two levels of kaoline clay 0 and 24 g L-1) affected aqueous malathion concentrations and toxicity in an aquatic invertebrate genus. Survival and acetylcholinesterase activity as a sub-organism response were examined in the mayfly Coloburiscoides spp. (Ephemeroptera; Coluburiscidae). Measured aqueous malathion concentrations decreased with increased pH and in the presence of kaolin clay. Survival declined with increasing malathion concentrations and exposure period. Results further identify that antagonism of malathion toxicity was associated with both pH (alkaline hydrolysis) and effects associated with sediment independent of pH (driven by sorptive processes). However, model predictions varied associated with target and measured concentrations and concentrations examined. Antagonistic effects were most apparent using subset target malathion concentrations because of the dominant effect of malathion at high concentrations. Acetylcholinesterase activity, identified repression occurred across all treatments and did not identify antagonistic interactions, but these results were similar to survival responses at the time points examined (i.e. 120 h). Examination of chemistry, acetylcholinesterase, and survival, affords greater understanding of stressor effects and their interactions. Measured malathion concentrations may underestimate effects on aquatic biota; not because of synergism among stressors, but because of strong effects despite antagonism.

Axion Dark Matter Experiment: Detailed design and operations.

Axion dark matter experiment ultra-low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the 2.66-3.1 µeV mass range with Dine-Fischler-Srednicki-Zhitnisky sensitivity [Du et al., Phys. Rev. Lett. 120, 151301 (2018) and Braine et al., Phys. Rev. Lett. 124, 101303 (2020)]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as the state-of-the-art quantum-noise-limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable microstrip superconducting quantum interference device amplifier in run 1A, and a Josephson parametric amplifier in run 1B, along with novel analysis tools that characterize the system noise temperature.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Diagnostic efficacy of and indications for intraoral radiographs in pediatric dentistry: a systematic review.

PURPOSE: To systematically evaluate the diagnostic efficacy of intraoral radiographs and evidence supporting the indications for taking of intraoral radiographs in children in the following five clinical categories: caries, pathological conditions (including acute odontogenic infections and periodontal disease), dental/developmental anomalies, dental trauma, and enhancement of comfort/technique for taking radiographs in children. This was carried out to facilitate the updating of existing European Academy of Paediatric Dentistry (EAPD) guidelines on dental radiography in pediatric dentistry. METHODS: A systematic electronic literature search was conducted on Cochrane Library (1992-24 July 2018), MEDLINE (PubMed, 1946-24 July 2018), EMBASE (Embase.com, 1974-24 July 2018) and Scopus (pre-1970-24 July 2018). Hand search of handbooks and grey literature search was also performed. Study screening and study inclusions were agreed upon by three authors. Data extraction, and methodological quality and risk of bias assessment were carried out in duplicate for each of the included studies. RESULTS: A total of 9581 papers were identified. Following the primary and secondary assessment process, 36 papers were included in the final analysis. The included studies were further categorized into five main clinical categories for analysis: caries, pathological conditions, dental/developmental anomalies, dental trauma and comfort/technique-related studies. Only one paper was found to be of good quality and at low risk of bias; while, 9 papers were found of be at moderate risk of bias and 26 papers were at high risk of bias. Meta-analysis was not possible for any of the aforementioned clinical situations, and only a narrative synthesis was done. CONCLUSION: There is insufficient high-quality evidence for the use of intraoral radiographs in pediatric dentistry and current guidelines are based largely on expert opinion. There is a clear need for well-conducted and standardized studies regarding the use of intraoral radiography in pediatric dentistry.

Extended Search for the Invisible Axion with the Axion Dark Matter Experiment.

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 µeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.

Revisiting the Significance of Prominent C Cells in the Thyroid.

C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.

Search for Invisible Axion Dark Matter with the Axion Dark Matter Experiment.

This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81 µeV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses.

Piezoelectrically Tuned Multimode Cavity Search for Axion Dark Matter.

The µeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.

A case report of concurrent embryonal rhabdomyosarcoma and diffuse large B-cell lymphoma in an adult without identifiable cancer predisposition.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently. CASE PRESENTATION: A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children's Oncology Group ARST 0331. CONCLUSIONS: This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.

Predictors for rehabilitation outcome in Asian geriatric hip fracture patients.

PURPOSE: To identify predictors for rehabilitation outcome in Asian geriatric hip fracture patients. METHODS: Records of 153 consecutive Asian patients aged 61 to 99 years who underwent surgery for hip fracture and were followed up for at least one year were reviewed. They were stratified into 4 agegroups: 60-69 years (n=27), 70-79 years (n=70), 80-89 years (n=50), and ≥90 years (n=6). Any comorbidity, regardless of severity, was recorded. Pre-injury and postoperative functional status was evaluated using the 36-item Short Form Health Survey. Relative functional gain (RFG) is equal to absolute functional gain (physical component summary [PCS] score at one year minus PCS score at 6 weeks) divided by the maximum potential gain (maximum PCS score minus PCS score at 6 weeks). RFG of <0.5 and ≥0.5 is defined as poor and good rehabilitation outcome, respectively. RESULTS: In univariate analysis, age 80-89 years (p=0.026), arthritis (p=0.082), and hypercholesterolaemia (p=0.014) were predictors for RFG. In multivariate analysis, age 80-89 years (p=0.016) remained a predictor for poor RFG, and hypercholesterolaemia remained a predictor for good RFG. CONCLUSION: Poor rehabilitation outcome was associated with patient age of 80-89 years; an orthogeriatric approach may be beneficial in optimising rehabilitation outcome in elderly hip fracture patients.

Acute bacterial osteomyelitis in children.

PURPOSE: To review the records of 24 paediatric patients treated for acute bacterial osteomyelitis. METHODS: Records of 14 male and 10 female paediatric patients (mean age, 9.4 years) who underwent medical treatment alone (n=3) or combined with surgery (n=21) for acute bacterial osteomyelitis were reviewed. Medical treatment included use of antibiotics and supportive care. Surgery was indicated when the largest dimension of fluid collection was >1 cm. RESULTS: Of the 24 patients, Staphylococcus aureus was isolated in 18, group-D salmonella in 3, and no organism in 3. The mean time from admission to diagnosis was 1.87 days. For those treated surgically, the mean time from diagnosis to surgery was 1.19 days and the mean time from admission to surgery was 2.86 days. Four patients underwent multiple surgeries, 2 of whom developed chronic osteomyelitis and also had negative culture and delayed surgery by >10 days previously. No other patient had any complications. CONCLUSION: Early surgical intervention for acute bacterial osteomyelitis in children increased diagnostic yield with cultures. For patients with fluid collection <1 cm in the largest dimension, medical treatment alone was effective. Patients with complications were characterised by negative culture, multiple surgeries, and delayed surgery.

Faecal incontinence in men referred for specialty care: a cross-sectional study.

AIM: Little is known about men with faecal incontinence. We compared clinical findings and quality of life in a large cohort of men and women with faecal incontinence to guide its evaluation and treatment in men. METHOD: We analysed men and women presenting to a tertiary referral centre with faecal incontinence between 2005 and 2013. Demographics, physical examination, anorectal physiology testing, symptom severity (Fecal Incontinence Severity Index) and quality of life (Fecal Incontinence Quality of Life Scale) were recorded. We determined differences between men and women and analysed the association between gender and quality of life. RESULTS: Data were obtained from 144 men and 897 women. Men with faecal incontinence were slightly younger than women (55.3 vs 57.6 years, P = 0.001), more likely to report coexisting constipation (P = 0.004) and more likely to have normal internal and external sphincter function on physical examination (both P < 0.001). Anorectal physiology testing revealed fewer sphincter defects (P < 0.05) and less pudendal neuropathy (P < 0.05) in men compared with women. Although symptom severity and overall quality of life were similar, men had improved coping and less embarrassment compared with women after we adjusted for important clinical factors. CONCLUSION: Men with faecal incontinence presenting to a tertiary referral centre are more likely than women to have a mixed presentation characterized by constipation and less sphincter dysfunction. They exhibited better coping and less embarrassment than women. These findings should be taken into consideration when evaluating and treating men with faecal incontinence.

Recurrent osteosarcoma with a single pulmonary metastasis: a multi-institutional review.

BACKGROUND: Late relapse and solitary lesion are positive prognostic factors in recurrent osteosarcoma. METHODS: We reviewed the records of 39 patients treated at three major centres for recurrent osteosarcoma with a single pulmonary metastasis more than 1 year after diagnosis. We analysed their outcomes with respect to clinical factors and treatment with chemotherapy. RESULTS: Median age at diagnosis was 14.6 years. Relapse occurred at a median of 2.5 years (range, 1.2-8.2 years) after initial diagnosis. At relapse, all patients were treated by metastasectomy; 12 (31%) patients also received chemotherapy. There was no difference in time to recurrence or nodule size between the patients who received or did not receive chemotherapy at relapse. Sixteen patients had no subsequent recurrence, 13 of whom survive without evidence of disease. The 5-year and 10-year estimates of post-relapse event-free survival (PREFS) were 33.0±7.5% and 33.0±9.6%, respectively, and of post-relapse survival (PRS) 56.8±8.6% and 53.0±11.0%, respectively. There was a trend for nodules <1.5 cm to correlate positively with PREFS (P=0.070) but not PRS (P=0.49). Chemotherapy at first relapse was not associated with PREFS or PRS. CONCLUSION: Approximately half of the patients with recurrent osteosarcoma presenting as a single pulmonary metastasis more than 1 year after diagnosis were long-term survivors. Metastasectomy was the primary treatment; chemotherapy did not add benefit.

Analysis of candidate genes for morphine preference quantitative trait locus Mop2.

Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine preference when tested using a two-bottle choice drinking paradigm. A morphine preference quantitative trait locus (QTL), Mop2, was originally mapped to proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed with reciprocal congenic strains and fine mapped with recombinant congenic strains. These efforts identified a ∼ 10-Million base pair (Mbp) interval, underlying Mop2, containing 35 genes. To further reduce the interval, mice from the D2.B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6-Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is one or more of 22 remaining within the newly defined interval (∼ 7.6 Mbp) which includes Oprm1 and several other genes related to opioid pharmacology. Real-time qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd revealed both between-strain and within-strain expression differences in comparisons of saline- and morphine-treated B6 and D2 mice. Analysis of Rgs17 protein levels also revealed both between-strain and within-strain differences in comparisons of saline- and morphine-treated B6 and D2 mice. Results suggest that the Mop2 QTL represents the combined influence of multiple genetic variants on morphine preference in these two strains. Relative contributions of each variant remain to be determined.

Adjuvant chemotherapy in elderly patients with pancreatic cancer.

BACKGROUND: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. METHODS: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. RESULTS: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ≥70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002). CONCLUSION: Patients aged ≥70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.

Mifamurtide in metastatic and recurrent osteosarcoma: a patient access study with pharmacokinetic, pharmacodynamic, and safety assessments.

PURPOSE: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. METHODS: Patients received mifamurtide 2 mg/m(2) intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24 hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. RESULTS: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30 minutes post-infusion, then in a log-linear manner 2-6 hours post-dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2 mg/m(2) mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills + fever or headache + fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N = 40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) CONCLUSIONS: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes.

Esophageal solid bolus transit: studies using combined multichannel intraluminal impedance and manometry in healthy volunteers.

The purpose of this study is to apply combined multichannel intraluminal impedance and esophageal manometry (MII-EM) to test esophageal function during solid swallowing in a normal healthy population. We determined whether combined MII-EM with solid bolus is more sensitive than that with viscous bolus in the detection of motility abnormality. Eighteen healthy volunteers (11 men and 7 women; mean age 22 years, range 20-26 years) underwent combined MII-EM with a catheter containing four impedance-measuring segments and five solid-state pressure transducers. Each subject received 10 viscous and 10 solid materials. Tracings were analyzed manually for bolus presence time, total bolus transit time, contraction amplitude, duration, and onset velocity. Three hundred and sixty swallows including viscous and solid materials were analyzed. Contraction amplitude for the viscous swallows was higher at 20 cm above the lower esophageal sphincter (LES) (P= 0.049) but lower at 15 cm above the LES (P < 0.001). Duration of contractions for the solid swallows was longer at 15 cm (P= 0.002) and 10 cm above the LES (P= 0.011) compared with viscous swallows. The total bolus transit time for solid was significantly shorter than that for viscous boluses (6.8 vs. 7.7 seconds, P < 0.001). Bolus presence time appeared to be similar between viscous and solid boluses (except in the proximal esophagus). The percentage of swallows with ineffective peristalsis by manometry, as well as those with incomplete bolus transit by impedance, did not differ between viscous and solid swallows. The proportion of manometrically ineffective solid swallows with incomplete bolus transit was greater than that of viscous swallows (62.1% vs. 34.8%, P= 0.05). Application of solid boluses may potentially enhance diagnostic capability of esophageal function testing. Solid boluses can be regarded as a valuable complement to viscous boluses in the detection of esophageal motility abnormalities when applied with combined MII-EM.