TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes.

BACKGROUND: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. RESULTS: Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. CONCLUSIONS: With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

Osteoporosis management in adults with schizophrenia following index hip fracture event: a 10-year population-based retrospective cohort study, Ontario, Canada.

Little is known about the incidence of osteoporosis testing and treatment in individuals with schizophrenia, who may be more likely to fracture. Using competing risk models, we found that schizophrenia was associated with lower incidence of testing or treatment. Implications are for understanding barriers and solutions for this disadvantaged group. PURPOSE: Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. METHODS: This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. RESULTS: A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). CONCLUSIONS: In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.

Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

Fetal cardiovascular changes during open and fetoscopic in-utero spina bifida closure.

OBJECTIVE: Laparotomy-assisted fetoscopic closure of spina bifida utilizing heated-humidified carbon dioxide gas has been associated with less maternal morbidity than open in-utero spina bifida closure. Fetal cardiovascular changes during these surgical interventions are not well defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR)<110 bpm over 10 minutes) and changes in umbilical artery Doppler parameters throughout open in-utero closure with those observed during laparotomy-assisted fetoscopic closure. METHODS: We conducted a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and umbilical artery velocimetry were systematically obtained during preoperative assessment, every 5 minutes during the intraoperative period, and in the postoperative assessment. FHR, pulsatility indexes and end-diastolic flows were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocities were measured in the fetoscopic cohort. Each fetal heart rate recording time point was correlated to maternal parameters, including heart rate, systolic and diastolic blood pressures. RESULTS: Fetal bradycardia occurred in 4/22 cases (18.2%) of open in-utero closure and in 21/46 cases (45.7%) of fetoscopic closure. FHR gradually decreased in both cohorts after general anesthesia and decreased further during surgery. FHR were significantly lower after two hours of surgery in the fetoscopic closure than in the open in-utero closure group. In addition, the FHR (BPM) change in the final stages of the fetal surgery from the baseline FHR was significantly lower in the fetoscopic cohort (-32.3 (-35.7, -29.1)) compared to the open cohort (-23.5 (-28.1, -18.8)) (p=0.002). Abnormal end-diastolic flow (defined as absent or reversed end-diastolic flow) in the umbilical artery Doppler velocity occurred in 3/22 (13.6%) of the open closure cohort and in 23/46 (50%) of the fetoscopic closure cohort (p=0.004). There were no differences in umbilical artery end-diastolic flow and pulsatility index between closure techniques during the various stages of assessment. CONCLUSIONS: We observed a decrease in the FHR and abnormalities in umbilical artery Doppler parameters in both open in-utero and fetoscopic closure groups. Fetal bradycardia was more prominent during fetoscopic closure following heated-humidified carbon dioxide insufflation, but the FHR recovered after cessation of the heated-humidified carbon dioxide. Changes in FHR and umbilical artery Doppler parameters during in-utero spina bifida closure were observed to be transient, no cases required emergency delivery and no fetoscopic closure were converted to open closure. These observations should inform algorithms for perioperative management of fetal bradycardia associated with in-utero spina bifida closure. This article is protected by copyright. All rights reserved.

Tetrahydrobenzothiophene derivatives ameliorate Mia PaCa-2 cell progression and induces apoptosis via inhibiting EGFR2 tyrosine kinase signal.

A series of new thiophene analogues with acarbonitrile-basedmoiety were designed and synthesized via structural optimization. The conjugates were assessed for their in-vitro cytotoxic activity against a human pancreatic cancer cell line (Mia PaCa-2) and among them compound 5b showed IC50 value of 13.37 ± 2.37 µM. The compounds 5b (20 µM & 25 µM) and 7c (30 & 35 µM) also showed reduced clonogenicity, enhanced ROS and decreased mitochondrial membrane potential in Mia PaCa-2 cells. Treatment with these compounds also increased apoptotic population as evident with the double staining assay. Among the evaluated series, compounds 5b, 5g, 7c, and 9a attained a greater inhibitory potency than first generation's reversible EGFR inhibitor, Gefitinib. EGFR2 enzyme inhibitory studies revealed that 5b efficiently and arbitrarily suppressed the development of EGFR2 dependent cells and inhibited the enzymatic activity with an IC50 value of 0.68 µM; interestingly, the most effective molecule 5b with N-methyl piperazine substitution, has 1.29-fold greater potency than well-known EGFR inhibitor Gefitinib and increased Gefitinib's anti-growth impact with 2.04 folds greater against Mia PaCa-2. The in-vitro studies were validated with in-silico docking studies wherein compounds 5b and 7c exhibited binding energies of -8.2 and -7.4 Kcal/mol respectively. The present study reveals that tetrahydrobenzothiophene based analogues could be a promising lead for the evolution of potent chemo preventives over pancreatic cancer.

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

Trends in clinical validation and usage of US Food and Drug Administration-cleared artificial intelligence algorithms for medical imaging.

AIM: To examine the current landscape of US Food and Drug Administration (FDA)-approved artificial intelligence (AI) medical imaging devices and identify trends in clinical validation strategy. MATERIALS AND METHODS: A retrospective study was conducted that analysed data extracted from the American College of Radiology (ACR) Data Science Institute AI Central database as of November 2021 to identify trends in FDA clearance of AI products related to medical imaging. Product and clinical validation information of each device was gathered from their respective public 510(k) summary or de novo request submission, depending on their type of authorisation. RESULTS: Overall, the database included a total of 151 AI algorithms that were cleared by the FDA between 2008 and November 2021. Out of the 151 FDA summaries reviewed, 97 (64.2%) reported the use of clinical data to validate their device, with six (4%) revealing study participant demographics, and eight (5.3%) reporting the specifications of the machines used. A total of 51 (33.8%) AI devices characterised their clinical data as multicentre, three (2%) as single-centre, and the remaining 97 (64.2%) did not specify. The ground truth used for clinical validation was specified in 78 (51.6%) FDA summaries. CONCLUSION: A wide breadth of AI algorithms has been developed for medical imaging. Most of the FDA summaries of the devices mention their use of clinical data and patient cases for device validation; however, few devices revealed the patient demographics or machine specifications used in their clinical studies, which may lead some consumers to question their external validation.

CLINICAL AND OBJECTIVE TEST CHARACTERISTICS OF VESTIBULAR MIGRAINE: IMPLICATIONS FOR DIAGNOSIS AND MANAGEMENT.

The research we provided look at a number of factors, such as age, unilateral testing, and squinting both during the ictal and interictal periods to define vestibular migraine. One hundred and ten adults with recurrent spontaneous and positional vertigo participated in the study, which the investigators did. Vestibular migraines (VM) or probable vestibular migraine constituted the two diagnoses given to the patients (n = 29 and n = 76, respectively). The findings revealed those surveyed frequently complained of headache (85.3%), spinning vertigo (76.2%), and Mal de Débarquement (60.2%), with movement hypersensitivity (32.6%). After an episode, 75.2% of individuals having vestibular migraine showed spontaneous squinting, whereas 16.5% did so among assaults, although fixing was forbidden. 27.3% of people had clear spatial squinting after an assault, while 57.3% did so after assaults. In 51.2% of instances, the direction of ictal spontaneous Nystagmus was straight, while in 19.5% of cases, it was vertical. Positional and spontaneously ictal squinting was evaluated at speeds between 0.0 and 59.3 degrees per second and 0.0 and 99.9 levels per minute, respectively. In 92.6% and 25.1% of instances, respectively, the interact spontaneous and positional nystagmus velocities were typically less than 3 degrees/second. When contrasted with the time within assaults, squinting speeds were substantially greater after an assault. According to additional tests, 98.6% of those tested exhibited normal lateral video head impulse test gains, indicating that their vestibule-ocular responses were in place. The calorie test findings were symmetrical in 86.4% of the instances, showing normal vestibular function. In 90.4% and 95.2% of cases misogynic potentials displayed symmetrical magnitudes. In 69.8% and 98.1% of instances, misogynic possibilities were identical. In 89.3% of cases, the audiometer data is generally uniform and age-consistent. In outcome, low-velocity squinting that can be horizontal, vertical, or torsional motions occur throughout a sensory migraines event. The investigation also discovered that patients with vestibular migraine often had acceptable audio vestibular test findings.

Fragility fracture patients with a history of prior fractures more likely to present with multiple risk factors: findings from a province-wide fracture liaison service.

We examined the demographic characteristics and risk factors of FLS fragility fracture patients who had sustained prior fragility fracture(s) and found that this is an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle. PURPOSE: Our primary objective was to examine whether fragility fracture patients presenting to a provincial fracture liaison service (FLS) having a history of prior fractures, versus those without, differ in demographic characteristics and risk factors for future fracture. A secondary objective was to understand if those who report two or more prior fractures differ from those reporting one prior fracture. METHODS: This cohort study included fragility fracture patients aged 50 + enrolled in the Ontario FLS between July 2017 and September 2019. Patients with versus those without prior fractures were compared on age, sex, index fracture site, biological parents' history of hip fracture, current fracture due to a fall, history of feeling unsteady when walking, history of falls in the past year, smoking, oral steroid use, and comorbid chronic conditions. Pearson's chi-square, Fischer's exact, and analysis of variance tests were used to assess differences. RESULTS: Among 14,454 patients, 16.8% (n = 2428) reported a history of one or more prior fractures after the age of 40. They were significantly more likely to be older, female, with a higher number of comorbidities, with greater incidence of falls, and feel unsteady when walking. Compared to those with one prior fracture, patients with greater than one prior fracture were more likely to report falls in the past year and feel unsteady when walking. CONCLUSION: Findings suggest that FLS fragility fracture patients who had sustained prior fragility fracture are an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle.

Patients not taking a previously prescribed bone active medication now prescribed medication through Ontario FLS.

In an Ontario fracture liaison service (FLS), we compared medication prescription rates among patients not taking a previously prescribed bone active medication to those with no previous prescription. Prescription rates were similar between these two groups of patients. The FLS provided a secondary opportunity for patients to initiate bone active medication. PURPOSE: We compared bone active medication prescription rates among patients presenting to an Ontario fracture liaison service (FLS) who reported not taking a previously prescribed bone active medication to those with no history of prescription. METHODS: Eligible patients were those screened in 39 fracture clinics between July 1, 2017, and September 15, 2019, who were not taking bone active medication at the time of screening and classified as high risk for future fracture based on CAROC or FRAX. Sociodemographic and clinical risk factor variables were assessed at screening. Bone active medication prescription rate was assessed within 6 months of screening and defined as having received a prescription for the medication from either a specialist or primary care provider. In cases where a specialist report was not available, patient self-reported data were collected. The chi-square test of independence was used to assess differences in prescription rates. RESULTS: Of 17,575 patients screened, eligible patients were 350 with a previous prescription and 2644 without a previous prescription. Compared with patients who reported no previous prescription, those who had a previous prescription were older, more likely to be female and to report a previous fracture, and less likely to smoke. There was no statistically significant difference between the medication prescription rate of patients with a previous prescription (73.7%) compared to patients with no previous prescription (70.7%) (p = 0.157). CONCLUSION: A large jurisdiction-wide FLS approach provided a secondary opportunity to patients who were not taking a previously prescribed bone active medication to initiate that medication.

Evidence of a Near-Threshold Resonance in

A narrow near-threshold proton-emitting resonance (E_{x}=11.4 MeV, J^{π}=1/2^{+}, and Γ_{p}=4.4 keV) was directly observed in ^{11}B via proton resonance scattering. This resonance was previously inferred in the ß-delayed proton emission of the neutron halo nucleus ^{11}Be. The good agreement between both experimental results serves as a ground to confirm the existence of such exotic decay and the particular behavior of weakly bound nuclei coupled to the continuum. R-matrix analysis shows a sizable partial decay width for both, proton and α (Γ_{α}=11 keV) emission channels.

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Confronting implicit bias toward patients: a scoping review of post-graduate physician curricula.

BACKGROUND: Physicians' behavior may unknowingly be impacted by prejudice and thereby contribute to healthcare inequities. Despite increasingly robust data demonstrating physician implicit bias (The Office of Minority Health. Minority Population Profiles, 2021; COVID-19 Shines Light on Health Disparities, National Conference of State Legislatures 2021), the evidence behind how to change this with training programs remains unclear. This scoping review therefore reports on the implementation, outcomes, and characteristics of post-graduate physician implicit bias curricula. METHODS: The authors conducted a literature review using scoping review methodology. They searched 7 databases in February and November 2020 for English-language academic and gray literature on implicit bias curricula for physicians at all levels of post-graduate training. Ten reviewers screened studies for eligibility independently, then extracted data from these studies and compiled it into a chart and analytical summary. RESULTS: Of the 4,599 articles screened, this review identified 90 articles on implicit bias interventions for post-graduate physicians. Inductive data analysis revealed a spectrum of educational approaches, which were categorized int o 4 educational models called Competence, Skills-Based, Social Contact, and Critical Models. The most commonly reported strength was the interactive nature of the curricula (26%), and the most frequently identified challenges were related to time and resources available (53%). Half of the interventions discussed facilitator preparation, and the majority (62%) evaluated outcomes using pre and post self-assessments. CONCLUSIONS: This review provides a comprehensive synthesis of the literature on physician implicit bias curricula. It is our goal that this supports medical educators in applying and improving aspects of these interventions in their own programs.

Patients 80 + have similar medication initiation rates to those aged 50-79 in Ontario FLS.

Among individuals presenting to an Ontario FLS, we compared bone active medication initiation rates of patients 80 years and older with those 50-79 years old. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates between the two age groups INTRODUCTION: A Fracture Liaison Service (FLS) offers post-fracture services to individuals over the age of 50 years and could potentially address age inequities in pharmacotherapy often observed for older adults. Among individuals presenting to an Ontario FLS and classified as being at high risk for future fracture, our objective was to compare bone active medication initiation rates of patients 80 years and older with those 50-79 years old. METHODS: In 39 FLS fracture clinics across Ontario, Canada, fracture prevention coordinators identified, assessed, and facilitated the referral of eligible patients for bone densitometry, fracture risk assessment, and implementation of pharmacotherapy in patients classified as high risk for future fracture. Variables assessed at baseline included age, sex, marital status, living location, fracture location, history of previous fracture, parent's history of hip fracture, history of falls, and fracture risk status. At 6 months, bone active medication initiation was assessed in patients classified as high risk for future fracture. The Chi-square test of independence was used to compare medication initiation rates between patients 80 + and those 50-79 years old. RESULTS: Our sample size consisted of 808 patients aged 50-79 years and 346 aged 80 + years. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates of patients 50-79 and 80 + years old (76.9% versus 73.7%, p = 0.251). CONCLUSION: A systematic approach to identifying patients at high risk for future fracture and tailoring treatment recommendations to these patients appeared to eliminate differences in treatment initiation rates based on older age.

Maslinic acid differentially exploits the MAPK pathway in estrogen-positive and triple-negative breast cancer to induce mitochondrion-mediated, caspase-independent apoptosis.

Breast cancer accounts for 1.4 million new cases every year. Triple-negative breast cancer (TNBC) is one the leading cause of mortality in developing countries and is associated with early age onset (under 40 years old). Chemotherapy has a poor success rate in patients with TNBC as compared to other types of breast cancers. It is due to the lack of expression of three validated molecular markers for breast cancer, the estrogen and progesterone receptors, and the amplification of HER-2/Neu. Therefore, a clear need exists for a greater understanding of TNBC at all levels and for the development of better therapies. We have studied the anti-tumor effects of a potential drug, maslinic acid, which can be extracted from olive oil industry waste. This natural product showed inhibitory effect at concentrations ranging from 30 to 50 µM within 24 h. It exhibited divergent effects in cell cycle progression for the MCF7 (estrogen positive) cell line when compared with TNBCs like MDA-MB-231 and MDA-MB-468. Also, maslinic acid treatment altered the mitochondrial membrane electrochemical potential and the reactive oxygen species (ROS) levels to cause a caspase-independent programmed cell death. In silico approaches and immunoblotting suggested the involvement of the MAPK pathway explaining the variability in cell cycle progression along with the apoptotic cell death caused by maslinic acid.

Fiber-based sources of coherent MIR radiation: key advances and future prospects (invited).

The mid-infrared (MIR) represents a large portion of the electromagnetic spectrum that is progressively being exploited for an enormous number of applications. Thermal imaging cameras, dental and skin resurfacing lasers, and narcotics detectors at airports are all mainstream examples involving the MIR, but potential applications of MIR technologies are much larger. Accessing the unique opportunities afforded by the MIR is critically dependent on the specific characteristics of MIR emitting sources that become available. In this review, we survey an important enabling technology to the opening up of MIR science and applications, namely that driven by fiber-based sources of coherent MIR radiation. In this review paper, we describe many of the key advances in the innovation and development of such sources over the past few decades and discuss many of the underlying science and technology issues that have resulted in specific recent source achievements, especially in light of new applications enabled by these new source capabilities. We also discuss a few specific anticipated future needs and some potentially disruptive approaches to future MIR fiber source development.

Luminescent ion-doped transparent glass ceramics for mid-infrared light sources [invited].

Glass ceramics (GCs), which consist essentially of a homogeneous solid state dispersion of nanocrystals (NCs) embedded in a chemically inert and mechanically robust glass matrix, appear to be an extremely promising class of solid state materials that can be easily tailored into arbitrary shapes, including a new generation of optical fibers, for efficient incoherent and coherent sources of mid-infrared (MIR) light emission. This unique capability not only stems from the fact that one can tailor the underlying glass matrix for optimal macroscopic physical properties and ultrahigh transparency at the wavelengths of interest (resulting in appropriate "transparent glass ceramics" or TGCs), but also stems from the fact that one can embed these matrices with size and structure-tailored NCs, which in turn can be doped with relatively high concentrations of MIR emitting rare-earth or transition metal ions. This potential is tantamount to the localization of these highly efficient MIR ionic emitters into carefully selected and highly favorable "process-engineered" custom crystalline host "nanocages," while insulating the ionic emitters from the emission-quenching glass host matrix, the latter being chosen largely because of its highly favorable macroscopic bulk properties, including its ductility and formability into near-arbitrary shapes (at appropriate temperatures). Such MIR TGCs appear to be very promising for numerous photonics applications, including compact and relatively efficient waveguide sensors, broadband incoherent MIR light sources, superluminescent light sources, advanced fiber-optic devices, and broadly wavelength-tunable and ultrashort pulse mode-locked fiber and bulk solid-state lasers. In this paper, we review past achievements in this field, starting with an overview of TGCs, followed by discussions of currently preferred methods of fabrication, characterization, and optimization of suitably doped oxyfluoride, tellurite, and chalcogenide TGCs and of our projections of anticipated future developments in this field at both the materials and device levels.

Using opportunistic screening with abdominal CT to identify osteoporosis and osteopenia in patients with diabetes.

Opportunistic osteoporosis screening involves measuring the attenuation of L1 vertebrae on abdominal computed tomography (CT), which correlates with DXA T-score. We found that this approach is useful for detecting low bone mass in patients with diabetes and propose L1 attenuation ≤ 135 Hounsfield units (HU) as a threshold for which DXA should be strongly considered. INTRODUCTION: Attenuation of the L1 vertebrae on computer tomography (CT) images done for other reasons ("Opportunistic Osteoporosis Screening") has been found to correlate well with DXA-derived T-score. However, the method and the thresholds have never been tested specifically in those with diabetes mellitus (DM), in whom the fracture risk is greater than explained by BMD. METHODS: In a retrospective study of subjects with DM who had both abdominal CT and DXA within 6 months of each other, we compared L1 attenuation and DXA T-score to define the sensitivity and specificity of thresholds previously established in the general population. RESULTS: There were 313 subjects among whom 18 (5.8%) had prior major osteoporotic fracture (MOF). Subjects with MOF had lower T-scores (- 2.3 ± 1.4 vs. - 0.9 ± 1.4, p < 0.001) and L1 attenuation (104 HU ± 46 vs. 149 HU ± 47, p < 0.001) than non-fracture subjects. L1 attenuation ≤ 160 HU was 91% sensitive for osteoporosis, while ≤ 110 HU was 80% specific. For a higher T-score of ≤ - 1.5, L1 attenuation ≤ 135 HU showed balanced sensitivity and specificity (65% and 69%, respectively). CONCLUSION: Opportunistic osteoporosis screening with abdominal CT is useful in determining the need for DXA screening in subjects with diabetes. We propose L1 attenuation ≤ 135 HU as a reasonable threshold for detecting the T-score of ≤ - 1.5, which is likely associated with increased fragility in DM.

Few fragility fracture patients perceive that their bone health is affected by their comorbidities and medications.

We examined fragility fracture patients' perceptions of associations between bone health and other chronic conditions and medications. Awareness of the associations between bone health and these conditions and medications was low. Providers should increase patients' awareness of these associations in order to minimize the risk of future fracture. INTRODUCTION: Among patients with a fragility fracture presenting with at least one other chronic health condition, we examined (1) perceptions of the association between bone health and their other health conditions, and (2) perceptions of the association between bone health and prescribed medications taken for other health conditions. METHODS: We identified fragility fracture patients presenting to a Canadian urban fracture clinic with at least one self-reported chronic health condition (in addition to bone fragility). In-depth interviews, 60-90 min in duration, were conducted. Our qualitative methodology was informed by saliency analysis. RESULTS: We interviewed 26 patients (21 females, 5 males) aged 45 to 84 years old. Participants were taking 1-13 medications each and presented with a variety of comorbidities (range 1-7). All participants described at least one condition or medication they were currently taking for which there existed evidence of a negative effect on bone health (increased risk of fracture, bone loss, falling). Two participants perceived a correct association between their other health conditions and compromised bone health, and four participants perceived a correct association between their medications and compromised bone health. CONCLUSION: All patients reported a chronic health condition and/or were taking at least one medication that potentially compromised their bone health. Patient awareness of the association between bone health and other health conditions and prescribed medications was low. Health care providers should increase patients' awareness of the bone health significance of their chronic conditions and medications in order to minimize the risk of future fracture.

Educational booklet reinforces knowledge of osteoporosis and influences intentions to improve bone health in previously diagnosed and treated patients.

We examined individuals' experiences using an educational booklet developed by the Ontario Osteoporosis Strategy. The booklet appeared to motivate individuals to make changes to their existing management of their bone health and served as a reference tool reaffirming current practices and beliefs for others. INTRODUCTION: The purpose of this study was to examine individuals' experiences of the educational booklet and explore the influence of the booklet on individuals' beliefs and actions regarding their bone health. METHODS: Eligible individuals were those who had been prescribed medication to treat low bone mass. One-on-one telephone interviews were conducted over an 18-month period. Participants were interviewed for approximately 1 hour and asked to provide their feedback on the booklet, and to discuss what they were doing with respect to the recommendations made in the booklet. RESULTS: We interviewed 50 participants who ranged in age from 58 to 89. The overall impression of the booklet was positive. Participants described the language in the booklet as clear and easy to understand. Participants stated that they would have appreciated receiving this tool at the onset of their diagnosis. Forty-two participants had already taken action, or expressed an intention to make changes, to their existing routines to improve their bone health. In contrast, eight participants used the booklet to reaffirm current practices and beliefs. For these individuals, the recommendations made in the booklet were consistent with what they had already been doing. CONCLUSION: The booklet can engage patients in discussions about bone health. The booklet appeared to motivate individuals to make changes to their existing routines in an effort to achieve better health outcomes for their bone health. Providing a tool like this to people recently diagnosed with a bone health issue may prove to be beneficial.