Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.

INTRODUCTION: We report results from a phase I, three-part, dose-escalation study of peposertib, a DNA-dependent protein kinase inhibitor, in combination with avelumab, an immune checkpoint inhibitor, with or without radiotherapy in patients with advanced solid tumors. MATERIALS AND METHODS: Peposertib 100-400 mg twice daily (b.i.d.) or 100-250 mg once daily (q.d.) was administered in combination with avelumab 800 mg every 2 weeks in Part A or avelumab plus radiotherapy (3 Gy/fraction × 10 days) in Part B. Part FE assessed the effect of food on the pharmacokinetics of peposertib plus avelumab. The primary endpoint in Parts A and B was dose-limiting toxicity (DLT). Secondary endpoints were safety, best overall response per RECIST version 1.1, and pharmacokinetics. The recommended phase II dose (RP2D) and maximum tolerated dose (MTD) were determined in Parts A and B. RESULTS: In Part A, peposertib doses administered were 100 mg (n = 4), 200 mg (n = 11), 250 mg (n = 4), 300 mg (n = 6), and 400 mg (n = 4) b.i.d. Of DLT-evaluable patients, one each had DLT at the 250-mg and 300-mg dose levels and three had DLT at the 400-mg b.i.d. dose level. In Part B, peposertib doses administered were 100 mg (n = 3), 150 mg (n = 3), 200 mg (n = 4), and 250 mg (n = 9) q.d.; no DLT was reported in evaluable patients. Peposertib 200 mg b.i.d. plus avelumab and peposertib 250 mg q.d. plus avelumab and radiotherapy were declared as the RP2D/MTD. No objective responses were observed in Part A or B; one patient had a partial response in Part FE. Peposertib exposure was generally dose proportional. CONCLUSIONS: Peposertib doses up to 200 mg b.i.d. in combination with avelumab and up to 250 mg q.d. in combination with avelumab and radiotherapy were tolerable in patients with advanced solid tumors; however, antitumor activity was limited. GOV IDENTIFIER: NCT03724890.

Detection Rates of Mild Cognitive Impairment in Primary Care for the United States Medicare Population.

BACKGROUND: Existing evidence points to substantial gaps in detecting mild cognitive impairment in primary care but is based on limited or self-reported data. The recent emergence of disease-modifying treatments for the Alzheimer's disease, the most common etiology of mild cognitive impairment, calls for a systematic assessment of detection rates in primary care. OBJECTIVES: The current study aims to examine detection rates for mild cognitive impairment among primary care clinicians and practices in the United States using Medicare claims and encounter data. DESIGN: Observational study. SETTING: Medicare administrative data. PARTICIPANTS: The study sample includes a total of 226,756 primary care clinicians and 54,597 practices that had at least 25 patients aged 65 or older, who were enrolled in Medicare fee-for-service or a Medicare Advantage plan between 2017 and 2019. MEASUREMENTS: The detection rate for mild cognitive impairment is assessed as the ratio between the observed diagnosis rate of a clinician or practice as documented in the data, and the expected rate based on a predictive model. RESULTS: The average detection rates for mild cognitive impairment is 0.08 (interquartile range=0.00-0.02) for both clinicians and practices, suggesting that only about 8% of expected cases were diagnosed on average. Only 0.1% of clinicians and practices had diagnosis rates within the expected range. CONCLUSIONS: Mild cognitive impairment is vastly underdiagnosed, pointing to an urgent need to improve early detection in primary care.

Factors associated with return-to-work outcomes in inpatient rehabilitation - a systematic scoping review.

Inpatient rehabilitation is common in Germany to improve return-to-work outcomes. The objective of this systematic scoping review was to identify factors associated with return-to-work outcomes in musculoskeletal, psychological and oncological health conditions to improve tailoring of rehabilitation therapies. A search was completed in Embase, Medline, PsycInfo and AMED until May 2023 for articles investigating inpatient rehabilitation including working-age patients with oncological, musculoskeletal, or psychological diseases using a quantitative design and reporting factors associated with return-to-work outcomes. Screening of all titles and abstracts was completed by one reviewer, full texts were read by two reviewers. Quality appraisal and data extraction was completed by two reviewers. Data was analysed using a narrative synthesis. Eighteen studies of moderate quality were included. The review identified a wide range of return-to-work parameters including employment status, work ability, sickness absence, retirement status and duration of employment since rehabilitation. In addition, 48 psychological, health- and work-related factors associated with return-to-work parameters were identified. Only one RCT investigated the relationship between a depression prevention intervention and a return-to-work outcome (work ability), which showed a significant effect. In addition to the depression prevention intervention, only the factor 'health literacy' could be considered modifiable and be addressed as part of an inpatient rehabilitation programme. Furthermore, gradual work reintegration programs and/or workplace interventions in addition to inpatient rehabilitation should be further explored to improve return-to-work outcomes.

Enabling elliptically polarized high harmonic generation with short cross polarized laser pulses.

Enabling elliptically polarized high-order harmonics overcomes a historical limitation in the generation of this highly nonlinear process in atomic, molecular and optical physics with applications in other branches. Here, we shed new light on a controversy between experimental observations and theoretical predictions on the possibility to generate harmonics with large ellipticity using two bichromatic laser pulses which are linearly polarized in orthogonal directions. Results of numerical calculations confirm the previous experimental data that in short laser pulses even harmonics with large ellipticity can be obtained for the interaction of such cross-polarized laser pulses with atoms initially in a s- or p-state, while odd harmonics have low ellipticity. The amount of the ellipticity can be controlled via the relative carrier-envelope phase of the pulses, their intensity ratio and the duration of the pulses.

Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

Do signs of abdominal wall injury on computed tomography predict intra-abdominal injury in trauma patients with a seatbelt sign?

BACKGROUND: A seatbelt sign in patients with blunt abdominal injury is associated with both abdominal wall and intra-abdominal injuries. This study aimed to assess the association between signs of abdominal wall injury on computed tomography (CT) and rates of intra-abdominal injury in patients with a blunt abdominal injury and a clinical seatbelt sign. METHODS: This study includes hemodynamically stable trauma patients with blunt abdominal injury and a clinical seatbelt sign who were hospitalized in two regional trauma centers in Israel, during 2014-2019. All data were collected via the medical center's trauma registry in both centers. RESULTS: We identified 123 stable blunt abdominal trauma patients with a seatbelt sign, of which 101 (82.1%) and 22 (17.9%) had a low-grade and high-grade abdominal wall injury according to CT findings, respectively. Laparotomy rates were significantly higher in patients with signs of high-grade abdominal wall injury (p<0.0001). No differences in the timing of laparotomy between low and high-grade injuries were found. CONCLUSIONS: In stable patients with blunt abdominal trauma and a clinical seatbelt sign, the severity of abdominal wall injury, as represented by CT findings, may predict a need for surgical treatment.

Murine typhus complicated by sHLH mimicking adult-onset Still's disease.

INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare multisystemic disorder and a diagnostic challenge for physicians because of the wide range of differential diagnoses. Common features of AOSD and secondary hemophagocytic lymphohistiocytosis (sHLH) could favour diagnostic uncertainty, in particular in case of infection-related sHLH. OBSERVATION: A 61-year-old man was admitted to our internal medicine department for suspected AOSD. He reported a 2-week history of sudden onset fever, headaches, myalgia, sore throat, diarrhoea, and an erythematous macular rash of the trunk as well as petechial purpuric lesions on both legs on return from Reunion Island. Laboratory tests found cytopenia, hepatic cytolysis, hypertriglyceridaemia, and hyperferritinaemia. Hemophagocytosis was diagnosed on bone marrow aspiration in favour of the diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH). Subcutaneous anakinra (100mg) was initiated to treat sHLH with favourable course. Oral doxycycline was added 3days later because of atypical features for AOSD diagnosis such as diarrhoea, hypergammaglobulinaemia, and doubtful serologies for Rickettsia and Coxiella. Three weeks later, Rickettsia typhi serology was checked again and revealed an increase in IgG titer>4 times that confirmed the diagnosis of murine typhus. A diagnosis of murine typhus complicated by sHLH was retained, successfully treated by anakinra and doxycycline. CONCLUSION: Our observation shows that AOSD diagnosis has to be stringent due to the many differential diagnoses, particularly infection complicated by sHLH, which may be rare. It is important to consider murine typhus in patients returning from endemic areas, such as La Reunion or other tropical areas, when they present fever of unknown origin with non-specific clinical features. Moreover, this case illustrates the effectiveness of IL-1 blockers as a treatment for symptomatic sHLH without severity criteria, regardless of the aetiology.

Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

End-to-side neurorrhaphy in peripheral nerves: Does it work?

Acute peripheral nerve injuries are common and can cause physical disabilities with sensory and functional sequelae; they therefore require surgery. The aim of this study was to conduct a systematic review to assess the clinical applicability of end-to-side neurorrhaphy in peripheral nerve reconstruction, based on available evidence. We carried out a systematic review of the literature using MEDLINE/PubMed, EMBASE, Cochrane Library, Web of Science, Scielo and Scopus through March 16, 2021. Most of the selected studies were qualitative and employed nonrandomized groups of patients, without standardized scales for assessing outcomes, which made statistical analysis difficult. Efficacy varied from 24% to 81%. Factors for better outcome included the type of injury, type of injured nerve (sensory, motor or mixed), presence of an epineural window, topography, injury extension <1.3 cm, and intervention within 2 weeks of injury. Clinical studies so far lack scientific evidence on end-to-side neurorrhaphy in peripheral nerve lesions.

Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Coherence in macroscopic high harmonic generation for spatial focal phase distributions of monochromatic and broadband Gaussian laser pulses.

Efficient application of ultrafast laser sources from high harmonic generation requires an understanding of how the spectrum can be controlled - the extent of the highest harmonics and the strength and cleanness of the harmonic lines. We study one important aspect in the coherent build-up of macroscopic high-order harmonic generation, namely the impact of different phase distributions in the focal area on the features of the generated radiation. Specifically, we compare the high harmonic signals for the commonly-used Gouy distribution of a monochromatic beam with those for the phase distribution of a short broadband Gaussian pulse. To this end, we apply a theoretical model in which the microscopic yields are obtained via interpolation of results of the time-dependent Schrödinger equation, which are then used in an individual-emitter approach to determine the macroscopic signals. Regions of poor and good coherent build-up as a function of the position of the gas jet are identified using measures for the strength of the harmonic lines and for the impact of off-harmonic radiation. While the largest extent of the spectra as well as the strongest contribution of off-harmonic radiation is found for positioning the gas jet after the focus for both distributions, the relative strength of the harmonics is overall weaker for the short Gaussian pulse distribution and the spectra differ for a gas jet positioned at the focus. These differences are mainly caused by the additional dependence of the focal phase in the transverse direction for the short Gaussian pulse distribution.

[Identification of rheumatological health apps in the Apple app store applying the "semiautomatic retrospective app store analysis" method : A longitudinal observation]. / Identifikation rheumatologischer Gesundheits-Apps im Apple App Store mit der Methode der "semiautomatischen retrospektiven App Store-Analyse" : Eine longitudinale Betrachtung.

BACKGROUND: The Apple and Google app stores offer a wide range of health apps. It is still a challenge to find valuable and qualified apps. OBJECTIVE: Can German language apps be identified using the "semiautomated retrospective app store analysis" (SARASA) method for the field of rheumatology? MATERIAL AND METHOD: The SARASA is a semiautomated method to select and characterize apps listed in the app store. After the first application in February 2018 SARASA was applied again to the Apple app store in February 2020. RESULTS: In February 2018 it was possible to acquire metadata for 103,046 apps and in February 2020 data for 94,735 apps that were listed in the category "health and fitness" or "medicine" in Apple's app store frontend for Germany. After applying the search terms 59 apps with a German language app description were identified for the field of rheumatology in 2018 and 53 apps in 2020. For these, more detailed manual reviews seem worthwhile. In 2018, the apps found were more likely to address patients than physicians and this was more balanced in 2020. In addition, it became apparent that for certain diseases there was no app developer activity. The percentage breakdown of matches by search term revealed substantial fluctuations in the app market when comparing 2018 to 2020. DISCUSSION: The SARASA method provides a useful tool to identify apps from app stores that meet predefined, formal criteria. Subsequent manual checks of the quality of the contents are still necessary. Further development of the SARASA method and consensus and standardization of quality criteria are worthwhile. Quality criteria should be considered for offers of mobile health apps in app stores.

Implementation of a uniform nationwide medical licensing examination in general practice. A feasibility study.

Objective: A competency-based training of medical students that is adapted to the realities of care is required internationally and is being intended in Germany with the Master Plan for Medical Studies 2020. In order to test these competencies, the German National Institute for state examinations in Medicine, Pharmacy and Psychotherapy (IMPP) has developed a concept for the redesign of the final part of the medical licensing examination in Germany. It focuses on general and interprofessional healthcare in the examination with outpatients. The aim of this work is to assess the feasibility of the new final examination on the basis of pilot examinations in family practices and to derive further steps for the national implementation. Methods: Fourteen medical students in their internship year completed a full examination with patients aged 42 to 84 years. Examiners evaluated the examination performance using standardised evaluation forms. Feasibility was qualitatively assessed in terms of compliance with content and time limits, examination results, patient reflections, and implementation in the practice. Results: Students were able to complete all tasks within the given time frame. Based on the evaluation forms, the examiners assessed the performance of the students. Patients appreciated the structured course of the examination in the familiar location of their family practice. For the nationwide implementation of the examination, 2,500 examination practices are required for about 10,000 examinees per year. Four students can then be examined on two days per year in each practice. Conclusions: Oral-practical examinations with outpatients in general medical practices can be carried out successfully throughout the nation. An implementation of the examinations throughout Germany requires that medical studies are restructured and that this new curriculum is implemented as intended by the Master Plan for Medical Studies 2020. Furthermore, training and remuneration of examiners together with a legal framework for the new examination must be established.

Characterization of vacuum and deep ultraviolet pulses via two-photon autocorrelation signals.

Characterization of ultrashort vacuum and deep ultraviolet pulses is important in view of applications of those pulses for spectroscopic and dynamical imaging of atoms, molecules, and materials. We present an extension of the autocorrelation technique, applied for measurement of the pulse duration via a single Gaussian function. Analytic solutions for two-photon ionization of atoms by Gaussian pulses are used along with an expansion of the pulse to be characterized using multiple Gaussians at multi-color central frequencies. This approach allows one to use two-photon autocorrelation signals to characterize isolated ultrashort pulses and pulse trains, i.e., the time-dependent amplitude and phase variation of the electric field. The potential of the method is demonstrated using vacuum and deep ultraviolet pulses and pulse trains obtained from numerical simulations of macroscopic high harmonic spectra.

The use of non-surgical glue to repair perineal first-degree lacerations in normal birth: A non-inferiority randomised trial.

BACKGROUND AND PROBLEM: Surgical glue has been indicated for uncomplicated operatory wounds; however, it has a considerable cost. Non-surgical glue, a commercially available and cheaper product, has not been studied for repairing postpartum lacerations. AIM: To compare non-surgical glue to traditional sutures on perineal first-degree lacerations after normal birth. METHODS: In a prospective, open-label, non-inferiority, randomised controlled trial, we selected childbearing women who were admitted for normal term births and in whom skin lacerations occurred. They were assigned to laceration repair using either non-surgical glue (ethyl 2-cyanoacrylate; Glue group) or catgut sutures (Suture group). The primary endpoint was the occurrence of dehiscence >3mm. Secondary endpoints were procedure runtime, pain score, satisfaction level, and aspects of perineal repair by the REEDA score (hyperaemia, oedema, ecchymosis, exudation, and coaptation) immediately (T0), 24-48h (T1), and 7-10 days (T2) after childbirth. FINDINGS: We included 126 women, 63 in each group, and found a non-inferiority dehiscence rate in the Glue Group compared to the Control group (T1=1.6% vs. 1.6%, P=0.999 and P<0.001 for non-inferiority; and T2=2.2% vs. 4.3%, P=0.557). In the Glue Group, the procedure runtime was shorter, pain score was lower, and women's satisfaction was greater. No women had any allergic reaction in the study. CONCLUSIONS: Non-surgical glue was not inferior to traditional sutures to repair postpartum first-degree lacerations. In addition, non-surgical glue was associated with less pain and greater satisfaction. Brazilian Clinical Trials Registry (www.ensaiosclinicos.gov.br/rg/RBR-5Z8MKC).

Evaluation of different target genes for the detection of Salmonella sp. by loop-mediated isothermal amplification.

The loop-mediated isothermal amplification (LAMP) technique was used to investigate six salmonella-specific sequences for their suitability to serve as targets for the pathogen identification. Sequences selected for designing LAMP primers were genes invA, bcfD, phoP, siiA, gene62181533 and a region within the ttrRSBCA locus. Primers including single nucleotide polymorphisms were configured as degenerate primers. Specificity of the designed primer sets was determined by means of 46 salmonella and 32 other food- and waterborne bacterial reference species and strains. Primers targeting the ttrRSBCA locus showed 100 % inclusivity of target and exclusivity of other test species and strains. Other primer sets revealed deficiencies, especially regarding Salmonella enterica subsp. II-IV and Salmonella bongori. Additionally, primers targeting the siiA gene failed to detect S. enterica subsp. enterica serotypes Newport and Stanley, whereas bcfD primers did not amplify DNA of S. enterica subsp. enterica serotype Schleissheim. TtrRSBCA primers, providing short detection times and constant melting temperatures of amplification products, achieved best overall performance.

Loop-mediated isothermal amplification: Development, validation and application of simple and rapid assays for quantitative detection of species of Arcobacteraceae family- and species-specific Aliarcobacter faecis and Aliarcobacter lanthieri.

AIM: The family Arcobacteraceae formerly genus Arcobacter has recently been reclassified into six genera. Among nine species of the genus Aliarcobacter, Aliarcobacter faecis and Aliarcobacter lanthieri have been identified as emerging pathogens potentially cause health risks to humans and animals. This study was designed to develop/optimize, validate and apply Arcobacteraceae family- and two species-specific (A. faecis and A. lanthieri) loop-mediated isothermal amplification (LAMP) assays to rapidly detect and quantify total number of cells in various environmental niches. METHODS AND RESULTS: Three sets of LAMP primers were designed from conserved and variable regions of 16S rRNA (family-specific) and gyrB (species-specific) genes. Optimized Arcobacteraceae family-specific LAMP assay correctly amplified and detected 24 species, whereas species-specific LAMP assays detected A. faecis and A. lanthieri reference strains as well as 91 pure and mixed culture isolates recovered from aquatic and faecal sources. The specificity of LAMP amplification of A. faecis and A. lanthieri was further confirmed by restriction fragment length polymorphism analysis. Assay sensitivities were tested using variable DNA concentrations extracted from simulated target species cells in an autoclaved agricultural water sample by achieving a minimum detection limit of 10 cells mL-1 (10 fg). Direct DNA-based quantitative detection, from agricultural surface water, identified A. faecis (17%) and A. lanthieri (1%) at a low frequency compared to family-level (93%) with the concentration ranging from 2·1 × 101 to 2·2 × 105 cells 100 mL-1 . CONCLUSIONS: Overall, these three DNA-based rapid and cost-effective novel LAMP assays are sensitive and can be completed in less than 40 min. They have potential for on-site quantitative detection of species of family Arcobacteraceae, A. faecis and A. lanthieri in food, environmental and clinical matrices. SIGNIFICANCE AND IMPACT OF THE STUDY: The newly developed LAMP assays are specific, sensitive, accurate with higher reproducibility that have potential to facilitate in a less equipped lab setting and can help in early quantitative detection and rate of prevalence in environmental niches. The assays can be adopted in the diagnostic labs and epidemiological studies.

Asymmetries in ionization of atomic superposition states by ultrashort laser pulses.

Progress in ultrafast science allows for probing quantum superposition states with ultrashort laser pulses in the new regime where several linear and nonlinear ionization pathways compete. Interferences of pathways can be observed in the photoelectron angular distribution and in the past they have been analyzed for atoms and molecules in a single quantum state via anisotropy and asymmetry parameters. Those conventional parameters, however, do not provide comprehensive tools for probing superposition states in the emerging research area of bright and ultrashort light sources, such as free-electron lasers and high-order harmonic generation. We propose a new set of generalized asymmetry parameters which are sensitive to interference effects in the photoionization and the interplay of competing pathways as the laser pulse duration is shortened and the laser intensity is increased. The relevance of the parameters is demonstrated using results of state-of-the-art numerical solutions of the time-dependent Schrödinger equation for ionization of helium atom and neon atom.