Imaging with an inverse-designed 50 mm-diameter f/1 MWIR flat lens with enhanced field of view and depth of focus.

We utilize inverse design and grayscale optical lithography to create a flat lens with a diameter and focal length of 50 mm, operating in the mid-wavelength infrared (MWIR) band. This lens demonstrates an extended depth of focus (DOF ≥±100µm), a field of view (FOV ≥20°), and an angular resolution of 300µrad. We characterize the lens's performance and use it as the primary optic in a hybrid refractive-diffractive telescope, which increases the angular resolution to 160µrad. Using this telescope, we perform video imaging of aircraft and vehicles. Our experiments were constrained by the higher f-number of the focal plane array. Nonetheless, through rigorous simulations, we demonstrate that the inverse-designed flat lens surpasses the performance of a conventional Fresnel zone plate (FZP) in DOF and in FOV, even under these limitations. The flat lens, weighing approximately 20g, is significantly lighter than its refractive counterparts, confirming the feasibility of high-resolution, lightweight MWIR imaging systems.

Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

Multilevel diffractive lens in the MWIR with extended depth-of-focus and wide field-of-view.

Optics in the mid-wave-infra-red (MWIR) band are generally heavy, thick and expensive. Here, we demonstrate multi-level diffractive lenses; one designed using inverse design and another using the conventional propagation phase (the Fresnel zone plate or FZP) with diameter = 25 mm and focal length = 25 mm operating at λ=4µm. We fabricated the lenses by optical lithography and compared their performance. We show that the inverse-designed MDL achieves larger depth-of-focus and better off-axis performance when compared to the FZP at the expense of larger spot size and reduced focusing efficiency. Both lenses are flat with thickness ≤0.5 mm and weigh ≤3.63 g, which are far smaller than their conventional refractive counterparts.

Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics.

PURPOSE: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics. METHODS: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines. RESULTS: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy. CONCLUSION: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.

Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications ("Sleep C.A.L.M.") in the evaluation and management of nocturia: A simple approach to a complex diagnosis.

INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.

Rethinking Routine Intensive Care After Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy: The Fiscal Argument.

BACKGROUND: Patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) are frequently admitted to the intensive care unit (ICU) for mitigation of potential complications, although ICU length of stay (LOS) is a significant driver of cost. This study asked whether a fiscal argument could be made for the selective avoidance of ICU admission after CRS/HIPEC. METHODS: Prospective data for select low-risk patients (e.g., lower peritoneal cancer index [PCI]) admitted to the intermediate care unit (IMC) instead of the ICU after CRS/HIPEC were matched with a historic cohort routinely admitted to the ICU. Cohort comparisons and the impact of the intervention on cost were assessed. RESULTS: The study matched 81 CRS/HIPEC procedures to form a cohort of 49 pre- and 15 post-intervention procedures for patients with similar disease burdens (mean PCI, 8 ± 6.7 vs. 7 ± 5.1). The pre-intervention patients stayed a median of 1 day longer in the ICU (1 day [IQR, 1-1 day] vs. 0 days [IQR, 0-0 days]) and had a longer LOS (8 days [IQR, 7-11 days] vs. 6 days [IQR, 5.5-9 days]). Complications and complication severity did not differ statistically. The median total hospital cost was lower after intervention ($30,845 [IQR, $30,181-$37,725] vs. $41,477 [IQR, $33,303-$51,838]), driven by decreased indirect fixed cost ($8984 [IQR, $8643-$11,286] vs. $14,314 [IQR, $12,206-$18,266]). In a weighted multiple variable linear regression analysis, the intervention was associated with a savings of $2208.68 per patient. CONCLUSIONS: Selective admission to the IMC after CRS/HIPEC was associated with $2208.68 in savings per patient without added risk. In this era of cost-conscious practice of medicine, these data highlight an opportunity to decrease cost by more than 5% for patients undergoing CRS/HIPEC.

LiMo8O10: Polar Crystal Structure with Infinite Edge-Sharing Molybdenum Octahedra.

Polycrystalline LiMo8O10 was prepared in a sealed Mo crucible at 1380 °C for 48 h using the conventional high-temperature solid-state method. The polar tetragonal crystal structure (space group I41md) is confirmed based on the Rietveld refinement of powder neutron diffraction and 7Li/6Li solid-state NMR. The crystal structure features infinite chains of Mo4O5 (i.e., Mo2Mo4/2O6/2O6/3) as a repeat unit containing edge-sharing Mo6 octahedra with strong Mo-Mo metal bonding along the chain. X-ray absorption near-edge spectroscopy of the Mo-L3 edge is consistent with the formal Mo valence/configuration. Magnetic measurements reveal that LiMo8O10 is paramagnetic down to 1.8 K. Temperature-dependent resistivity [ρ(T)] measurement indicates a semiconducting behavior that can be fitted with Mott's variable range hopping conduction mechanism in the temperature range of 215 and 45 K. The ρ(T) curve exhibits an exponential increase below 5 K with a large ratio of ρ1.8/ρ300 = 435. LiMo8O10 shows a negative field-dependent magnetoresistance between 2 and 25 K. Heat capacity measurement fitted with the modified Debye model yields the Debye temperature of 365 K.

Parker Solar Probe Imaging of the Night Side of Venus.

We present images of Venus from the Wide-Field Imager for Parker Solar Probe (WISPR) telescope on board the Parker Solar Probe (PSP) spacecraft, obtained during PSP's third and fourth flybys of Venus on 2020 July 11 and 2021 February 20, respectively. Thermal emission from the surface is observed on the night side, representing the shortest wavelength observations of this emission ever, the first detection of the Venusian surface by an optical telescope observing below 0.8 µm. Consistent with previous observations at 1 µm, the cooler highland areas are fainter than the surrounding lowlands. The irradiances measured by WISPR are consistent with model predictions assuming a surface temperature of T = 735 K. In addition to the thermal emission, the WISPR images also show bright nightglow emission at the limb, and we compare the WISPR intensities with previous spectroscopic measurements of the molecular oxygen nightglow lines from Venus Express.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

Design, synthesis, and biological evaluation of novel pyrido-dipyrimidines as dual topoisomerase II/FLT3 inhibitors in leukemia cells.

Dual inhibition of topoisomerase (topo) II and FLT3 kinase, as in the case of C-1311, was shown to overcome the shortcomings of using topo II inhibitors solely. In the present study, we designed and synthesized two series of pyrido-dipyrimidine- and pseudo-pyrido-acridone-containing compounds. The two series were evaluated against topo II and FLT3 as well as the HL-60 promyelocytic leukemia cell line in vitro. Compounds 6, 7, and 20 showed higher potency against topo II than the standard amsacrine (AMSA), whereas compounds 19 and 20 were stronger FLT3 inhibitors than the standard DACA. Compounds 19 and 20 showed to be dual inhibitors of both enzymes. Compounds 6, 7, 19, and 20 were more potent inhibitors of the HL-60 cell line than the standard AMSA. The results of the in vitro DNA flow cytometry analysis assay and Annexin V-FITC apoptosis analysis showed that 19 and 20 induced cell cycle arrest at the G2/M phase, significantly higher total percentage of apoptosis, and late-stage apoptosis in HL-60 cell lines than AMSA. Furthermore, 19 and 20 upregulated several apoptosis biomarkers such as p53, TNFα, caspase 3/7 and increased the Bax/Bcl-2 ratio. These results showed that 19 and 20 deserve further evaluation of their antiproliferative activities, particularly in leukemia. Molecular docking studies were performed for selected compounds against topo II and FLT3 enzymes to investigate their binding patterns. Compound 19 exerted dual fitting inside the active site of both enzymes.

Computational Modeling of Drying of Pharmaceutical Wet Granules in a Fluidized Bed Dryer Using Coupled CFD-DEM Approach.

Drying of wet granules in a fluidized bed dryer is an important part of the pharmaceutical tablet manufacturing process. Complicated gas-solid flow patterns appear in the fluidized bed dryer, and interphase momentum, heat, and mass transfer happen during the drying process. A coupled computational fluid dynamics (CFD)-discrete element method (DEM)-based approach was used to model the drying process of pharmaceutical wet granules in a fluidized bed dryer. The evaporation of water from the surfaces of the particles and the cohesion force between the particles due to the formation of liquid bridges between the particles were also considered in this model. The model was validated by comparing the model predictions with the experimental data available from the literatures. The validated model was used to investigate the drying kinetics of the wet granules in the fluidized bed dryer. The results from numerical simulations showed that the dynamics and rate of increase of temperature of wet particles were considerably different from those of dry particles. Finally, the model was used to investigate the effects of inlet air velocity and inlet air temperature on the drying process. The model predicted increase in drying rate with the increase of inlet air velocity and inlet air temperature. This model can help not only to understand the multiphase multicomponent flow in fluidized bed dryer but also to optimize the drying process in the fluidized bed dryer.

Cytomegalovirus Coinfection in Critically Ill Patients with Novel Coronavirus-2019 Disease: Pathogens or Spectators?

Coronavirus disease-2019 (COVID-19) pandemic is raging all over the world. As we are delving more into management of COVID-19, certain new challenges are emerging. One of these is emergence or reactivation of viral infections belonging to Herpesviridae family, especially cytomegalovirus (CMV). Although we have come across the threat of fungal and resistant bacterial infections, experience regarding reactivation or coinfection with concomitant viral infections like CMV during the COVID pandemic is still limited. Whether CMV is a bystander or pathogen is difficult to say categorically and needs further research. In this case series, we intend to describe three patients of COVID-19 with CMV coinfections. To our knowledge, this is the first case series from India. How to cite this article: Siddiqui SS, Chatterjee S, Yadav A, Rai N, Agrawal A, Gurjar M, et al. Cytomegalovirus Coinfection in Critically Ill Patients with Novel Coronavirus-2019 Disease: Pathogens or Spectators? Indian J Crit Care Med 2022;26(3):376-380.

Phenotyping the Association between Nocturia and Hypertension: A Systematic Review and Meta-Analysis.

PURPOSE: The association between nocturia and hypertension has been widely reported yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the clinical urology setting. We synthesized current evidence on the relationship between nocturia and hypertension as a function of nocturia severity, age, gender, race, body mass index and diuretic use. MATERIALS AND METHODS: We searched PubMed®, EMBASE® and Cochrane databases for studies published up to May 2020. Random effects meta-analyses were performed to identify pooled odds ratios for nocturia given the presence of hypertension. Meta-regression and subgroup analyses were performed to identify differences across study samples. RESULTS: Of 1,193 identified studies, 25 met the criteria for inclusion. The overall pooled OR for the association of nocturia with hypertension was 1.25 (95% CI 1.21-1.28, p <0.001). Pooled estimates were 1.20 (1.16-1.25, p <0.001) and 1.30 (1.25-1.36, p <0.001) using a 1-void and 2-void cutoff for nocturia, respectively (p <0.001 between cutoffs). The association was more robust in patient-based (1.74 [1.54-1.98], p <0.001) vs community-based (1.24 [1.24-1.29], p <0.001) study samples (p <0.001). The association was stronger in females compared to males (1.45 [1.32-1.58] vs 1.28 [1.22-1.35], p <0.001), and Black (1.56 [1.25-1.94]) and Asian (1.28 [1.23-1.33]) vs White subgroups (1.16 [1.08-1.24]; p <0.05 for both). No effect was observed for age or body mass index. Evidence on diuretics was limited. CONCLUSIONS: Hypertension is associated with a 1.2-fold to 1.3-fold higher risk of nocturia. This association is more robust at a higher nocturia cutoff, in patient-based study samples, among females and in Black and Asian patients, but unrelated to age or body mass index.

Tunable In Situ 3D-Printed PVDF-TrFE Piezoelectric Arrays.

In the functional 3D-printing field, poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) has been shown to be a more promising choice of material over polyvinylidene fluoride (PVDF), due to its ability to be poled to a high level of piezoelectric performance without a large mechanical strain ratio. In this work, a novel presentation of in situ 3D printing and poling of PVDF-TrFE is shown with a d33 performance of up to 18 pC N-1, more than an order of magnitude larger than previously reported in situ poled polymer piezoelectrics. This finding paves the way forward for pressure sensors with much higher sensitivity and accuracy. In addition, the ability of in situ pole sensors to demonstrate different performance levels is shown in a fully 3D-printed five-element sensor array, accelerating and increasing the design space for complex sensing arrays. The in situ poled sample performance was compared to the performance of samples prepared through an ex situ corona poling process.

Blinding in Clinical Trials: Seeing the Big Picture.

Blinding mitigates several sources of bias which, if left unchecked, can quantitively affect study outcomes. Blinding remains under-utilized, particularly in non-pharmaceutical clinical trials, but is often highly feasible through simple measures. Although blinding is generally viewed as an effective method by which to eliminate bias, blinding does also pose some inherent limitations, and it behooves clinicians and researchers to be aware of such caveats. This article will review general principles for blinding in clinical trials, including examples of useful blinding techniques for both pharmaceutical and non-pharmaceutical trials, while also highlighting the limitations and potential consequences of blinding. Appropriate reporting on blinding in trial protocols and manuscripts, as well as future directions for blinding research, will also be discussed.

Foundational Statistical Principles in Medical Research: Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value.

Sensitivity, which denotes the proportion of subjects correctly given a positive assignment out of all subjects who are actually positive for the outcome, indicates how well a test can classify subjects who truly have the outcome of interest. Specificity, which denotes the proportion of subjects correctly given a negative assignment out of all subjects who are actually negative for the outcome, indicates how well a test can classify subjects who truly do not have the outcome of interest. Positive predictive value reflects the proportion of subjects with a positive test result who truly have the outcome of interest. Negative predictive value reflects the proportion of subjects with a negative test result who truly do not have the outcome of interest. Sensitivity and specificity are inversely related, wherein one increases as the other decreases, but are generally considered stable for a given test, whereas positive and negative predictive values do inherently vary with pre-test probability (e.g., changes in population disease prevalence). This article will further detail the concepts of sensitivity, specificity, and predictive values using a recent real-world example from the medical literature.

Identifying men with global polyuria on a nocturnal-only voiding diary.

AIMS: Nocturnal polyuria (NP) and global polyuria (GP) are not mutually exclusive. However, by rate, the common criteria for GP (40 mL/kg/24 hours [117 mL/kg/hour in a 70-kg individual] or 3000 mL/24 hours [125 mL/h]) are more stringent than those for NP (90 mL/hour during the sleep period or NP index [NPi; nocturnal volume/24-hour volume] > 0.33 [no minimum rate]). It remains unclear whether total nocturnal urine volume (NUV) may reliably delineate between NP patients with and without comorbid GP. METHODS: A clinical database of men with lower urinary tract symptoms was searched for voiding diaries completed by patients reporting greater than or equal to 1 nocturnal void(s). Four separate analyses were performed using all combinations of the two NP and two GP criteria listed above. For each analysis, patients were included if they met the criteria for NP, and then stratified by presence or absence of GP (ie, NP + GP vs isolated NP). RESULTS: Median NUV was greater among patients with NP + GP for all criteria combinations. Sensitivities greater than or equal to 80%/90%/100% for NP + GP were observed at 1275/1230/1085 mL for {NPi > 0.33 + 24-hour volume > 3000 mL}; 1075/1035/1035 mL for {NPi > 0.33 + 24-hour volume > 40 mL/kg}; 900/745/630 mL for {NUP > 90 mL/hour + 24-hour volume > 3000 mL}; and 1074/1035/990 mL for {NUP > 90 mL/hour + 24-hour volume > 40 mL/kg}. CONCLUSIONS: An inordinate NUV among men with NP is fairly sensitive for comorbid GP. In the appropriate clinical setting, nocturnal-only diaries may suffice in the evaluation and follow-up of patients with NP, so long as outlying nocturnal volumes prompt a 24-hour diary/urine collection.

Association between nocturia and frailty among elderly males in a veterans administration population.

BACKGROUND: The relationship between frailty and nocturnal voiding is poorly understood. AIM: To characterize the association between frailty, as defined by a frailty index (FI) based upon the Canadian Study of Health and Aging (CSHA) criteria, and nocturia, defined by measures of nocturnal urine production. METHODS: Real-world retrospective analysis of voiding diaries from elderly males with lower urinary tract symptoms (LUTS) at an outpatient urology clinic. Males ≥ 65 years with ≥ 2 nocturnal voids were included. A modified FI was calculated from the LUTS database, which captured 39 variables from the original CSHA FI. Patients were divided into 3 groups by modified FI: low (≤ 0.077) (n = 59), intermediate (> 0.077 and < 0.179) (n = 58), and high (≥ 0.179) (n = 41). Diary parameters were compared using the Kruskal-Wallis test and pairwise comparisons with the Wilcoxon rank-sum test and Bonferroni adjustment. RESULTS: The high frailty group was characterized by higher nocturnal urine volume (NUV), maximum voided volume (MVV), nocturnal maximum voided volume (NMVV), and nocturnal urine production (NUP). The presence of comorbid diabetes mellitus did not explain this effect. CONCLUSION: Elderly males seeking treatment for LUTS with a high frailty burden are disproportionately affected by excess nocturnal urine production. Future research on the mechanistic relationship between urine production and functional impairment is warranted.

Correction to: Association between nocturia and frailty among elderly males in a veterans administration population.

In the original publication of the article, the author's name Jeffrey P. Weiss was misspelled as "Jeffry P. Weiss".

Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease.

In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (ßA) aggregation and ß-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.