Geographical differences in chronic obstructive pulmonary disease mortality trends by sex, Spain, 1980-2021.

BACKGROUND: To analyse changes in trends in mortality due to chronic obstructive pulmonary disease (COPD) in Spain by Autonomous Community (AC) and sex during the period 1980-2021.METHODS: Data on population and COPD death records (International Classification of Diseases, 10th edition, codes J40â-"J44 and J47) were retrieved from the National Institute of Statistics for the study period. Age-standardised mortality rates by AC and sex were assessed using joinpoint regression models.RESULTS: There were 562,668 deaths due to COPD (423,855 in men and 138,813 in women), with an average annual increase of 1.6%. COPD deaths in men increased in most ACs, except for Asturias (â-"0.5% per year). The Canary Islands (14% per year) and Madrid (6.5% per year) had the highest increases. In women, the figures show a wide range of values at the AC level (from a â-"1.4% decrease to 7.9% increase). Nationally, the sex ratio increased from 1980 to 2021. In men, six ACs showed a significant decrease, while in women only two ACs showed a significant decrease.CONCLUSION: A steady decrease in COPD mortality was observed in most ACs for men, while a different trend was observed in women in several ACs. Despite past and ongoing tobacco control initiatives, this condition remains a leading cause of death.

Tightly locked optical frequency comb from a semiconductor disk laser.

Ultrafast semiconductor disk lasers (SDLs) passively modelocked using semiconductor saturable absorbers mirrors (SESAMs) generate optical frequency combs (OFCs) with gigahertz line spacings - a regime where solid-state and fiber lasers struggle with geometrical and Q-switching limitations. We stabilized both the frequency comb spacing and the offset without any additional external optical amplification or pulse compression. The overall noise performance is competitive with other gigahertz OFCs. A SESAM-modelocked vertical external-cavity surface-emitting laser (VECSEL) at a center wavelength around 1 µm generates 122-fs pulses with 160 mW average output power and we only needed 17-pJ pulse energy coupled into a silicon nitride (Si3N4) waveguide for supercontinuum generation (SCG) and OFC offset stabilization.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

Direct thermo-optical tuning of silicon microresonators for the mid-infrared.

We use light from a visible laser diode to directly tune silicon-on-chip microresonators by thermo-optical effect. We show that this direct tuning is local, non invasive and has a much smaller time constant than global temperature tuning methods. Such an approach could prove to be highly effective for Kerr comb generation in microresonators pumped by quantum cascade lasers, which cannot be easily tuned to achieve comb generation and soliton-mode locked states.

Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

Liver Allocation in Urgent MELD Score ≥30: The Italian Experience.

INTRODUCTION: Patients with an urgent MELD score ≥30 are managed by the Italian Operative National Transplant Center on the basis of a division of Italy into 2 main areas, the northern macro area (NMA) and the southern macro area (SMA). The object of this study was to evaluate the possibility and the need to transform the MELD score ≥30 macro area-based program into a nationwide one. PATIENTS AND METHODS: When a region reports the presence of a patient with a MELD score ≥30, the same macro area-compatible donors, in the absence of urgent national and 1B status, are offered primarily to this recipient. RESULTS: From August 2014 to August 2015, 132 requests for patients with urgent MELD score ≥30, 98 from the NMA and 34 from the SMA, were handled. The average waiting list in the NMA was significantly different from that of the SMA (2.74 ± 2.29 vs 4.5 ± 3.98, P < .05). A total of 73.7% of the received requests (n = 97) were satisfied: the NMA met 80.4% of the requests (n = 77), whereas the SMA met 55.5% (n = 20). A total of 35 requests (26.5%), 21 from the NMA (60%) and 14 (40%) from the SMA, were not met. The average waiting time of these recipients for a liver was significantly different between the NMA and the SMA (3.14 ± 3.21 vs 5.78 ± 4.59; P < .05). CONCLUSIONS: The MELD score is a priority allocation, and the longer the waiting time to transplantation for these recipients, the more their mortality increases. Given the differences in waiting times between the NMA and SMA, we should start thinking about transforming the macro area program into a national one.

Transportation of Organs by Air: Safety, Quality, and Sustainability Criteria.

INTRODUCTION: The outcomes of organ transplantation activities are greatly affected by the ability to haul organs and medical teams quickly and safely. Organ allocation and usage criteria have greatly improved over time, whereas the same result has not been achieved so far from the transport point of view. Safety and the highest level of service and efficiency must be reached to grant transplant recipients the healthiest outcome. OBJECTIVES: The Italian National Transplant Centre (CNT), in partnership with the regions and the University of Bologna, has promoted a thorough analysis of all stages of organ transportation logistics chains to produce homogeneous and shared guidelines throughout the national territory, capable of ensuring safety, reliability, and sustainability at the highest levels. METHODS: The mapping of all 44 transplant centers and the pertaining airport network has been implemented. An analysis of technical requirements among organ shipping agents at both national and international level has been promoted. A national campaign of real-time monitoring of organ transport activities at all stages of the supply chain has been implemented. Parameters investigated have been hospital and region of both origin and destination, number and type of organs involved, transport type (with or without medical team), stations of arrival and departure, and shipping agents, as well as actual times of activities involved. RESULTS: National guidelines have been issued to select organ storage units and shipping agents on the basis of evaluation of efficiency, reliability, and equipment with reference to organ type and ischemia time. Guidelines provide EU-level standards on technical equipment of aircrafts, professional requirements of shipping agencies and cabin crew, and requirements on service provision, including pricing criteria. CONCLUSIONS: The introduction in the Italian legislation of guidelines issuing minimum requirements on topics such as the medical team, packaging, labeling, safety and integrity, identification, real-time monitoring of temperature, and traceability of the organ during the logistics chain is deemed a valid response to the necessity of improving safety, reliability, and sustainability of organ transplantation activities in Italy.

Solid Organ Transplantation in HIV+ Recipients: Italian Experience.

INTRODUCTION: According to current estimates, there are about 540,000 patients who are infected with HIV in Western Europe, of which about 3100 are potential candidates for organ transplantation. In Italy, there are currently 85 HIV patients on the transplant list. METHODS: Organ transplantation activity in HIV recipients from 2002 to December 2014 was assessed from the database provided by the Transplant Center of Modena until the year 2011. For the years 2012 to 2014, data are from the Transplant Information System (SIT). The follow-up data have been extracted from the function "Quality" of the SIT. RESULTS: The transplant centers on Italian territory that meet the requirements according to national protocol are in total 29: 11 for the liver, 9 for the kidney including 1 pediatric, 3 for the heart, 3 for the lungs, and for 3 for the combined kidney-pancreas. Since 2002, 257 organ transplantations were carried out, including 185 liver, 59 kidney, 5 combined liver-kidney, 5 combined kidney-pancreas, 2 heart, and 1 double lung. The first cause of death is represented by co-hepatitis C virus infection, in particular in 26 liver recipients (37%) and in 3 kidney recipients (20%). CONCLUSIONS: The analysis showed that transplantation activity in HIV is on the rise, especially in the last 2 years, with an outcome similar to that reported in the literature.

Frequency comb offset detection using supercontinuum generation in silicon nitride waveguides.

We present the first direct carrier-envelope-offset (CEO) frequency detection of a modelocked laser based on supercontinuum generation (SCG) in a CMOS-compatible silicon nitride (Si(3)N(4)) waveguide. With a coherent supercontinuum spanning more than 1.5 octaves from visible to beyond telecommunication wavelengths, we achieve self-referencing of SESAM modelocked diode-pumped Yb:CALGO lasers using standard f-to-2f interferometry. We directly obtain without amplification strong CEO beat signals for both a 100-MHz and 1-GHz pulse repetition rate laser. High signal-to-noise ratios (SNR) of > 25 dB and even > 30 dB have been generated with only 30 pJ and 36 pJ of coupled pulse energy from the megahertz and gigahertz laser respectively. We compare these results to self-referencing using a commercial photonic crystal fiber and find that the required peak power for CEO beat detection with a comparable SNR is lowered by more than an order of magnitude when using a Si(3)N(4) waveguide.

Detection and quantification of EBV, HHV-6 and CMV DNA in the gastrointestinal tract of HIV-positive patients.

Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63%; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

Ultrabroadband supercontinuum generation in a CMOS-compatible platform.

We demonstrate supercontinuum generation spanning 1.6 octaves in silicon nitride waveguides. Using a 4.3 cm-long waveguide, with an effective nonlinearity of γ=1.2 W(-1) m(-1), we generate a spectrum extending from 665 nm to 2025 nm (at -30 dB) with 160 pJ pulses. Our results offer potential for a robust, integrated, and low-cost supercontinuum source for applications including frequency metrology, optical coherence tomography, confocal microscopy, and optical communications.

Long-term enzyme replacement therapy in a severe case of mucopolysaccharidosis type II (Hunter syndrome).

Hunter syndrome or mucopolysaccharidosis II (MPS II) is a rare X-linked disease caused by a deficiency of the iduronate-2-sulphatase (12S) lysosomal enzyme, resulting in a progressive accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) with recombinant human 12S idursulfase has been used infrequently in children < 5 years. We present the case of a 7 years and 10 months-old child, who was diagnosed with a severe form of MPS II at the age of 3 years, and who began a 36 months' treatment with idursulfase at 4 years 10 months. After 10 months, GAG urinary excretion was normal, but after just 4 months the liver and spleen had decreased in size, returning to normal limits by 36 months. Significant bone remodeling was noted after 16 months. Cardiac and neurological development, however, progressively deteriorated. The only adverse reactions were episodic inflammations of the upper and/or lower respiratory tract, but there was no otitis. Early use of ERT, presuming good treatment adherence, can significantly improve bone abnormalities.

Novel and potent tacrine-related hetero- and homobivalent ligands for acetylcholinesterase and butyrylcholinesterase.

Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed.

Multiplex polymerase chain reaction for the evaluation of cytomegalovirus DNA load in organ transplant recipients.

Because of the considerable impact of human cytomegalovirus (HCMV) infection, sensitive, specific, and standardized methods are required for rapid and accurate evaluation of viral load in monitoring transplant recipients. The aim of the present study was to evaluate the usefulness of a multiplex polymerase chain reaction (PCR) for the coamplification of HCMV-DNA and beta-globin genomic sequence in polymorphonuclear leukocytes (PMNL). Analysis and quantification of PCR products were carried out by a DNA enzyme immunoassay (DEIA), which is based on the hybridization of amplified DNA with a single-stranded DNA probe, which coats microtitre wells. Colorimetric detection of the DNA-antibody complex was carried out and optical density (O.D.) was recorded at 450/630 nm. To quantify HCMV/DNA load, a standard curve to which samples O.D. refer was obtained by amplifying serial dilutions of recombinant PGEM-3Z plasmid DNA containing a genomic fragment of glycoprotein B. 340 PMNL specimens from 102 solid organ recipients were tested for the detection of pp65 antigen and HCMV-DNA. The results showed a good correlation between viral load and clinical symptoms of HCMV infection; high specificity and predictive values for HCMV disease were found by PCR, using a cut-off limit of 10(3) genomic copies per 2 x 10(5) PMNL. These findings indicate that the system described is an efficient and reproducible diagnostic method easy to apply for routine diagnosis and therapeutic monitoring of transplanted patients.

Critical power for self-focusing in bulk media and in hollow waveguides.

We determine the threshold power for self-focusing collapse both in a bulk medium and in a hollow-core waveguide for various spatial profiles. We find that the threshold power for collapse in the waveguide is always equal to the lower-bound prediction for a bulk medium.

Nonlinear propagation dynamics of an ultrashort pulse in a hollow waveguide.

We present a theoretical investigation of the self-focusing dynamics of femtosecond pulses in a hollow waveguide. We show that transverse effects play an important role in these dynamics, even for pulses that are significantly below the critical power for self-focusing in free space, and that excitation of higher-order modes of the waveguide results in the spreading of the pulse in time. Inclusion of self-steepening and space-time focusing in our model is necessary for properly capturing the pulse dynamics.

Infrared photosensitivity in silica glasses exposed to femtosecond laser pulses.

We investigate the use of infrared femtosecond laser pulses to induce highly localized refractive-index changes in fused-silica glasses. We characterize the magnitude of the change as a function of exposure and measure index changes as large as 3x10(-3) and 5x10(-3) in pure fused silica and boron-doped silica, respectively. The potential of this technique for writing three-dimensional photonic structures in bulk glasses is demonstrated by the fabrication of a Y coupler within a sample of pure fused silica.

Breakdown of the slowly varying envelope approximation in the self-focusing of ultrashort pulses.

We show theoretically and experimentally that with ultrashort pulses much longer than a single optical cycle, the effects of self-steepening and space-time focusing are important for describing the nonlinear dynamics of self-focusing. Asymmetric temporal splitting of the pulse envelope is observed in which the relative magnitudes of the peaks are reversed as the input power is increased.

Femtosecond ultraviolet autocorrelation measurements based on two-photon conductivity in fused silica.

We utilize the two-photon conductivity of a fused-silica substrate to produce a photoconductive switch for use in an intensity autocorrelator for ultraviolet ultrashort pulses. We perform measurements at 267 nm with pulse durations in the range of 110-330 fs and with energies as weak as 10 nJ. Based on the bandgap of fused silica, this device can potentially operate in the wavelength range of 140-280 nm.