Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Preliminary searches for spin-dependent interactions using sidebands of nuclear spin-precession signals.

Various theories beyond the Standard Model predict new particles with masses in the sub-eV range with very weak couplings to ordinary matter. A new P-odd and T-odd interaction between polarized and unpolarized nucleons proportional to s⃗⋅r̂ is one such possibility, where r⃗=rr̂ is the spatial vector connecting the nucleons, and s⃗ is the spin of the polarized nucleon. Such an interaction involving a scalar coupling gsN at one vertex and a pseudoscalar coupling gpn at the polarized nucleon vertex can be induced by the exchange of spin-0 pseudoscalar bosons. We describe a new technique to search for interactions of this form and present the first measurements of this type. We show that future improvements to this technique can improve the laboratory upper bound on the product gsNgpn by two orders of magnitude for interaction ranges at the 100 micron scale.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Disease-related complications in patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records. RESULTS: The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission. CONCLUSION: Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system.

Erratum: Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator [Phys. Rev. Lett. 129, 080401 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.080401.

Final Result of the Majorana Demonstrator's Search for Neutrinoless Double-ß Decay in

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

Genome-wide identification and expression analysis of SlRR genes in response to abiotic stress in tomato.

The cytokinin two-component signal transduction system (TCS) is involved in many biological processes, including hormone signal transduction and plant growth regulation. Although cytokinin TCS has been well characterized in Arabidopsis thaliana, its role in tomato remains elusive. In this study, we characterized the diversity and function of response regulator (RR) genes, a critical component of TCS, in tomato. In total, we identified 31 RR genes in the tomato genome. These SlRR genes were classified into three subgroups (type-A, type-B and type-C). Various stress-responsive cis-elements were present in the tomato RR gene promoters. Their expression responses under pesticide treatment were evaluated by transcriptome analysis. Their expression under heat, cold, ABA, salinity and NaHCO3 treatments was further investigated by qRT-PCR and complemented with the available transcription data under these treatments. Specifically, SlRR13 expression was significantly upregulated under salinity, drought, cold and pesticide stress and was downregulated under ABA treatment. SlRR23 expression was induced under salt treatment, while the transcription level of SlRR1 was increased under cold and decreased under salt stress. We also found that GATA transcription factors played a significant role in the regulation of SlRR genes. Based on our results, tomato SlRR genes are involved in responses to abiotic stress in tomato and could be implemented in molecular breeding approaches to increase resistance of tomato to environmental stresses.

Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator.

The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.

Search for Solar Axions via Axion-Photon Coupling with the Majorana Demonstrator.

Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g_{aγ}<1.45×10^{-9} GeV^{-1} (95% confidence level) for axions with mass up to 100 eV/c^{2}. This improves laboratory-based limits between about 1 eV/c^{2} and 100 eV/c^{2}.

[Exploratory study on detection of drug resistance of Mycobacterium tuberculosis in sputum specimens by next-generation sequencing].

Objective: To compare the diagnostic performance of next-generation sequencing (NGS) detection methods in sputum samples and Mycobacterium tuberculosis strains, in order to explore the feasibility of the NGS method to detect drug resistance in sputum specimens. Methods: In this retrospective study, the sputum specimens and corresponding clinical isolates of 50 pulmonary tuberculosis patients admitted to Beijing Chest Hospital from January 2017 to December 2017 were collected. The gene mutations of katG, inhA, rpoB, embA, embB, rpsL, rrs, gyrA, gyrB and tlyA in sputum specimens and corresponding clinical isolates were detected by NGS method. The phenotypic drug susceptibility test (DST) of the strains was carried out by the proportion method. Using DST results as a reference, the sensitivity, specificity, positive predictive value and negative predictive value of the NGS method for clinical strains and sputum specimens, as well as the consistency statistic (Kappa) with phenotype DST were calculated respectively. The Chi-square test was used to compare the accuracy of the NGS testing in sputum samples and strain samples. Results: The results showed that rpoB(63.83%, 30/47) and rrs(57.45%, 27/47) were the most common mutated genes, followed by katG(46.81%, 22/47), rpsL(29.79%, 14/47), gyrA(27.66%, 13/47), embB(21.28%, 10/47), tlyA(12.77%, 6/47), gyrB(8.51%, 4/47), and inhA promoter(19.15%, 9/47), embA promoter region (12.77%, 6/47) mutation. when the NGS method was compared with the resistance phenotype of isoniazid, rifampicin, ethambutol, second-line injectable drugs (streptomycin, capreomycin, kanamycin, amikacin), levofloxacin, the sensitivity were 85.71%, 91.67%, 77.78%, 81.82%, 100.00%, 87.50%, 100.00%, 69.23%, and the specificity were 100.00%, 94.12, 87.50%, 89.47%, 97.06%, 96.97%, 94.29%, 89.29% in sputum samples, while in strain samples, the sensitivity were 92.86%, 100.00%, 81.82%, 86.96%, 88.89%, 80.00%, 100.00%, 85.71%. The specificity were 100.00%, 92.86%, 87.10%, 94.74%, 100.00%, 100.00%, 97.14%, 92.86%. Compared with the phenotypic drug susceptibility results, the NGS method has better detection performance for isoniazid, rifampicin, capreomycin, kanamycin, and amikacin in sputum specimens (Kappa≥0.75); while among the strains, the NGS method had a good detection performance for isoniazid, rifampicin, streptomycin, capreomycin, kanamycin, amikacin and levofloxacin (Kappa≥0.75). With the accuracy of the NGS method for detecting strains as a reference, there was no statistically significant difference in the accuracy of all drug resistance detected between strains and sputum specimens. Conclusions: This study showed that the NGS technology was effective in predicting the resistance of isoniazid, rifampicin, and second-line injectable drugs (capreomycin, kanamycin and amikacin) by detecting sputum samples and strain genotypes, suggesting the feasibility and potential of direct detection of sputum samples by the NGS method as an early detection method for drug resistance.

[Clinical characteristics and prognostic analyses of cervical neuroblastoma].

Objective: To determine the characteristics of cervical neuroblastoma and the effect of resection extent on survival and outcomes. Methods: We performed a retrospective review of 32 children with cervical neuroblastoma treated at Beijing Children's Hospital between April 2013 and August 2020. Data were collected from the medical record. The individualized therapy was designed based on staging and risk group. Based on the extent of resection, patients were divided into incomplete and complete resection groups. Event free and overall survival rates were compared between two groups using the Kaplan-Meier method. Results: The ages of patients ranged from 1 month to 81 months, with a median age of 11 months, including 7 males and 15 females. Twenty-nine patients (90.6%) presented with cervical painless mass. The average diameter of the primary tumors was (5.12±1.43) cm. Tumors were located in the parapharyngeal space in 25 cases (78.1%) and in the root of the neck in 7 cases (21.9%). None had MYCN amplification. According to International Neuroblastoma Staging System (INSS), 15 patients (46.9%) were identified as stage 1, 11 patients (34.3%) as stage 2B, 3 patients (9.4%) as stage 3 and 3 patients (9.4%) as stage 4. There were 12 patients (37.5%) at low risk, 17 patients (53.1%) at intermediate risk and 3 patients at high risk according to Children's Oncology Group (COG) risk classification system. All patients underwent tumor resection. Postoperatively Horner's syndrome occurred in 13 patients (40.6%), pneumonia in 9 patients (28.1%), pharyngeal dysfunction in 8 patients (25.0%) and transient hoarseness in 4 patients (12.5%). At a median follow-up of 36.5 months, the overall survival rate was 96.4%, with no significant difference between incomplete and complete resection groups (100.0% vs. 96.3%, χ2=0.19, P=0.667); the event free survival rate was 78.1%, with a significant difference between the two groups (40.0% vs. 85.2%, χ²=6.71, P=0.010). Conclusions: Primary cervical neuroblastoma has a young onset age, mostly in low and medium risk groups, and represents favorable lesions with good outcomes after multidisciplinary therapy. Less aggressive surgery with preservation of important structures is recommended. Complete resection should not be attempted if it would compromise vital structures.

α -event characterization and rejection in point-contact HPGe detectors.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0 ν ß ß ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0 ν ß ß region of interest window by an order of magnitude in the Majorana Demonstrator  and will be used in the upcoming LEGEND-200 experiment.

Repurposing Proton Beam Therapy through Novel Insights into Tumour Radioresistance.

Despite improvements in radiotherapy, radioresistance remains an important clinical challenge. Radioresistance can be mediated through enhanced DNA damage response mechanisms within the tumour or through selective pressures exerted by the tumour microenvironment (TME). The effects of the TME have in recent times gained increased attention, in part due to the success of immune modulating strategies, but also through improved understanding of the downstream effects of hypoxia and dysregulated wound healing processes on mediating radioresistance. Although we have a better appreciation of these molecular mechanisms, efforts to address them through novel combination approaches have been scarce, owing to limitations of photon therapy and concerns over toxicity. At the same time, proton beam therapy (PBT) represents an advancement in radiotherapy technologies. However, early clinical results have been mixed and the clinical strategies around optimal use and patient selection for PBT remain unclear. Here we highlight the role that PBT can play in addressing radioresistance, through better patient selection, and by providing an improved toxicity profile for integration with novel agents. We will also describe the developments around FLASH PBT. Through close examination of its normal tissue-sparing effects, we will highlight how FLASH PBT can facilitate combination strategies to tackle radioresistance by further improving toxicity profiles and by directly mediating the mechanisms of radioresistance.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

Correction: Role of integrin-linked kinase in regulating the protein stability of the MUC1-C oncoprotein in pancreatic cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide implementation and audit leads to improved value and patient outcomes.

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.