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High-directivity and low-loss directional couplers based on Empty Substrate Integrated Coaxial Line (ESICL) technology are presented in this article. The proposed coupled line directional couplers are based on the combination of a high-isolation section, a tapered transition based on splines between the access lines and the high-isolation sections, coupled lines of reduced width and inclined arms. The design evolution has justified the combination and precise adjustment of these elements, proving to be a solution to increase directivity, improve return losses and achieve a more stable coupling coefficient. The use of ESICL technology shows great promise in terms of electrical performance, bandwidth, seamless integration with other planar circuits and ease of manufacture. For comparison, two directional couplers with the same coupling coefficient but different operating frequencies have been designed and fabricated. A microstrip coupler was also designed and fabricated for comparison. The simulated and measured results clearly show that the ESICL directional couplers outperform their microstrip counterparts in terms of losses and directivity, without the need for additional lumped elements or complex geometries.

Synthetic Aperture Radar (SAR) has become, nowadays, one of the most important techniques in remote-sensing, and the increasing interest in Earth monitoring reinforces this trend. Next-generation SAR sensors will enhance the radar resolution capabilities by means of digital beamforming (DBF) techniques along with multistatic systems. In order to support the technological development of future spaceborne SAR missions, airborne sensors become an essential scope of research. Thereby, future airborne SAR systems demand enhanced DBF capabilities that involve phased array antennas with a high density of array elements. However, the antenna aperture size is significantly limited in airborne applications, which leads to low-profile and highly integrated antenna solutions, becoming a more challenging task for lower frequency operations such as L-band. In this work, a compact L-band dual-polarized multilayer phased array antenna with beam steering in elevation, developed for the next-generation German Aerospace Center (DLR) airborne SAR system, is presented. The proposed design makes use of truncated cavities to improve the array element isolation and provides 66% more antenna elements than the previous L-band phased array of the current DLR airborne SAR sensor with the same antenna aperture size. Measurements of a manufactured prototype show an antenna bandwidth of almost 20%, matching levels better than 17 dB, up to 15 dB gain, and cross-polarization suppression values higher than 35 dB. Thus, the proposed work will allow the application of advanced DBF techniques in the upcoming first pulsed bistatic L-band airborne SAR sensor.

El objetivo del presente estudio bibliométrico consistió en analizar la producción científica acumulada sobre los factores de riesgo biopsicosocial conducentes al suicidio en la infancia y la adolescencia mediante la implementación de la teoría de grafos. Se consultaron las bases de datos Scopus (Elsevier) y Web of Science, y el análisis se efectuó en bibliometrix, Sci2 tool y Gephi. Se encontraron 2,058 registros. El análisis mostró una red de citaciones de 2,905 registros y cuatro clústeres principales. Los resultados arrojaron una estructura de red de la producción de conocimiento en cuatro tendencias de investigación: (1) factores de predicción de tipo psiquiátrico del comportamiento suicida en niños y adolescentes; (2) asociación entre conducta autolesiva no suicida y comportamiento suicida en adolescentes; (3) relación entre maltrato infantil y suicidio; (4) uso de antidepresivos en la niñez y adolescencia y comportamiento suicida. Finalmente, se plantean consideraciones para la prevención del suicidio en la población objeto de estudio.

This article presents the theoretical study, numerical simulation and fabrication of a phase shifter and a stub resonator for use in microstrip ridge gap waveguide (MRGW) technology, using a liquid crystal (LC) in the substrate as a reconfigurable material. The phase shifter and the stub resonator are filled with LC, and thanks to the LC’s dielectric anisotropy properties, the phase shift and the resonance response can be easily controlled using an external electric or magnetic bias field. The phase shifter was designed to operate in the range of 10 to 20 GHz, and the resonator was designed to operate in the range of 7.8 to 8.8 GHz. The phase shifter’s responses (including both phase shift and insertion losses), associated with both the parallel and perpendicular permittivity values of the LC, were computed and measured, and then the corresponding figure of merit (FoM) was extracted. The resonator’s frequency responses, associated with both the LC’s parallel and perpendicular permittivity, were computed. The resonator’s frequency responses, which provided different polarization voltages, were measured and compared to the simulation results. All technological issues related to both prototypes are also discussed here. The good agreement between the simulation and measurement results confirm this technology as a viable approach to the practical implementation of these microwave reconfigurable devices.

Introduction: The course of autosomal dominant polycystic kidney disease (ADPKD) varies greatly among affected individuals, necessitating natural history studies to characterize the determinants and effects of disease progression. Therefore, we conducted an observational, longitudinal study (OVERTURE; NCT01430494) of patients with ADPKD. Methods: This prospective study enrolled a large international population (N = 3409) encompassing a broad spectrum of ages (12–78 years), chronic kidney disease (CKD) stages (G1–G5), and Mayo imaging classifications (1A–1E). Outcomes included kidney function, complications, quality of life, health care resource utilization, and work productivity. Results: Most subjects (84.4%) completed ≥12 months of follow-up. Consistent with earlier findings, each additional l/m of height-adjusted total kidney volume (htTKV) on magnetic resonance imaging (MRI) was associated with worse outcomes, including lower estimated glomerular filtration rate (eGFR) (regression coefficient 17.02, 95% confidence interval [CI] 15.94–18.11) and greater likelihood of hypertension (odds ratio [OR] 1.25, 95% CI 1.17–1.34), kidney pain (OR 1.22, 95% CI 1.11–1.33), and hematuria (OR 1.35, 95% CI 1.21–1.51). Greater baseline htTKV was also associated with worse patient-reported health-related quality of life (e.g., ADPKD Impact Scale physical score, regression coefficient 1.02, 95% CI 0.65–1.39), decreased work productivity (e.g., work days missed, regression coefficient 0.55, 95% CI 0.18–0.92), and increased health care resource utilization (e.g., hospitalizations, OR 1.48, 95% CI 1.33–1.64) during follow-up. Conclusion: Although limited by a maximum 3-year duration of follow-up, this observational study characterized the burden of ADPKD in a broad population and indicated the predictive value of kidney volume for outcomes other than kidney function.

This article describes the use of dielectric rods to reconfigure combline filters both with respect to center frequency and bandwidth. In this context, a new filter topology is developed in order to maximize the achievable reconfiguration range. The design of a prototype is discussed in detail, clearly demonstrating the feasibility of center frequency and bandwidth reconfiguration, with the same filter structure, while maintaining an equiripple return loss. In addition to theory, a combline filter prototype is also fabricated, tuned and measured in several configurations showing excellent agreement with simulations, thereby fully validating both the basic concept and the design procedure.

In this paper, a very efficient procedure for designing waveguide combline bandpass filters with an advanced electrical response is presented. The proposed technique is based on a segmentation strategy, which reduces the number of variables to be optimized by dividing the design process into simpler stages. The electrical response of an appropriate equivalent circuit model of the waveguide structure considered in each stage is used to generate the target curve needed in the optimization process. Moreover, the well-known Aggressive Space Mapping technique has been also implemented to improve the computational efficiency of the whole method. In order to validate the proposed design procedure, two high-order combline bandpass filters, with symmetric and asymmetric electrical responses including transmission zeros, have been successfully designed and simulated with full-wave analysis tools. Furthermore, as an experimental validation, a prototype of the symmetric filter has been manufactured, showing a good agreement between simulated and experimental data.

In this paper, we discuss how the use of the recently developed modified tuning pin (MTP) can be extended to the design of filters and diplexers implemented in rectangular waveguide, that can be reconfigured in a number of discrete states, and that can be used in high-power payloads. As an application example, the design of two reconfigurable filters and a reconfigurable diplexer is fully described. The high-power behavior of these components (in particular, with respect to corona and multipaction effects) is also studied in detail, in order to demonstrate that the structures that we discuss can operate correctly under high-power conditions. Furthermore, comparisons between simulations and measurements of several prototypes are also included, showing an excellent agreement between simulated and experimental data, thereby fully validating both the design approach and the filter reconfiguration strategy.

Abstract An integral equation technique for the analysis of multiport H‐plane microwave circuits composed of an unlimited number of arbitrarily shaped metallic and/or dielectric elements is proposed. The structure under study is divided into different regions after the application of the surface equivalence principle. Following this approach, the access waveguide ports are modelled by means of parallel plate Green's functions, whereas the central region is characterised by 2D rectangular cavity Green's functions. The use of this kind of Green's functions represents a novelty for solving H‐plane integral equation problems. For the first time, the Ewald method has been employed in order to accelerate the computation of the 2D rectangular cavity Green's functions and their derivatives, needed in the integral equation. In addition, convergence studies show the numerical convenience of using the Ewald method to achieve a fast and accurate evaluation of these Green's functions. Results show that the analysis can be very efficient if the structure is segmented in a proper way based on fitting the cavity resonator within the geometry of the structure under analysis. In fact, all the walls of the structure that are coincident with the auxiliary resonator need not to be discretised during the numerical solution. Finally, several simulation examples of practical inductive microwave circuits are presented and discussed, showing a good agreement and higher computational efficiency when compared to results provided by commercial full‐wave software tools and measurements.

In this paper, a miniaturized wideband bandpass filter in coaxial substrate integrated waveguide (SIW) technology is presented. To improve the response selectivity and coupling control, a multi-layer structure has been implemented, introducing both strong magnetic and electric couplings. To reduce the physical size of the device, surfaced-mounted device (SMD) capacitors have been integrated on the top layer. These allow both resonant frequency and capacitive coupling level control. Thus, a 4-th order Chebyshev filter with an absolute bandwidth (BW) of 2.9 GHz centered at 5.35 GHz has been designed, fabricated and measured. An extremely small filter size of $7 \times 7$ ,mm2 has been obtained. A study of manufacturing tolerances are also presented in this paper, together with a post-manufacturing response correction allowed by the SMD elements. As it is shown in the paper, the filter’s out-of-band rejection can be easily enhanced by introducing additional transmission zeros (TZs).

The progression of autosomal dominant polycystic kidney disease (ADPKD), an inherited kidney disease, is associated with renal interstitial inflammation and fibrosis. CD74 has been known not only as a receptor of macrophage migration inhibitory factor (MIF) it can also have MIF independent functions. In this study, we report unknown roles and function of CD74 in ADPKD. We show that knockout of CD74 delays cyst growth in Pkd1 mutant kidneys. Knockout and knockdown of CD74 (1) normalize PKD associated signaling pathways, including ERK, mTOR and Rb to decrease Pkd1 mutant renal epithelial cell proliferation, (2) decrease the activation of NF-κB and the expression of MCP-1 and TNF-alpha (TNF-α) which decreases the recruitment of macrophages in Pkd1 mutant kidneys, and (3) decrease renal fibrosis in Pkd1 mutant kidneys. We show for the first time that CD74 functions as a transcriptional factor to regulate the expression of fibrotic markers, including collagen I (Col I), fibronectin, and α-smooth muscle actin (α-SMA), through binding on their promoters. Interestingly, CD74 also regulates the transcription of MIF to form a positive feedback loop in that MIF binds with its receptor CD74 to regulate the activity of intracellular signaling pathways and CD74 increases the expression of MIF in ADPKD kidneys during cyst progression. We further show that knockout of MIF and targeting MIF with its inhibitor ISO-1 not only delay cyst growth but also ameliorate renal fibrosis through blocking the activation of renal fibroblasts and CD74 mediated the activation of TGF-β-Smad3 signaling, supporting the idea that CD74 is a key and novel upstream regulator of cyst growth and interstitial fibrosis. Thus, targeting MIF-CD74 axis is a novel therapeutic strategy for ADPKD treatment.

ADPKD is caused by pathogenic variants in PKD1 or PKD2, encoding polycystin-1 and -2 proteins. Polycystins are expressed in osteoblasts and chondrocytes in animal models, and loss of function is associated with low bone mineral density (BMD) and volume. However, it is unclear whether these variants impact bone strength in ADPKD patients. Here, we examined BMD in ADPKD after kidney transplantation (KTx). This retrospective observational study retrieved data from adult patients who received a KTx over the past 15 years. Patients with available dual-energy X-ray absorptiometry (DXA) of the hip and/or lumbar spine (LS) post-transplant were included. ADPKD patients (n = 340) were matched 1:1 by age (±2 years) at KTx and sex with non-diabetic non-ADPKD patients (n = 340). Patients with ADPKD had slightly higher BMD and T-scores at the right total hip (TH) as compared to non-ADPKD patients [BMD: 0.951 vs. 0.897, p

3D printing is one of the most promising manufacturing methods in the most developed technological fields, including microwave hardware fabrication. On the other hand, the well-known manufacturing methods of planar substrate integrated circuits allow high-quality prototypes to be made at low cost and with mass production capabilities. The combination of both manufacturing methods, 2D or 2.5D (substrate integrated circuits) and 3D (3D printed structures), will allow us to take advantage of the main strengths of each technology and minimise disadvantages. In this article, for the first time, a transition structure between the Empty Substrate-Integrated Waveguide (ESIW) technology—a planar waveguide integrated on a printed circuit board—and a standard rectangular waveguide manufactured by 3D printing is proposed. This transition will make it possible to combine planar circuits with 3D structures, thus taking advantage of the benefits of both types of technologies. The fabricated prototype presents low losses (0.6 dB for the transmission coefficient and 15 dB for reflection coefficient), good electrical response (very flat), and simultaneously good mechanical stability and robustness to manufacturing and assembly errors. The proposed design for this transition piece is easily realisable for a wide range of affordable 3D printers. Repeatability is guaranteed and the proposed transition allows us to combine different SIC structures to 3D printed circuits. Hence, this transition will enable advancements in the fabrication of microwave devices, particularly with regard to satellite communications.

Background: No dairy breed or crossbreed has superior overall performance in all environments; therefore, it is necessary to determine which crossbreed is the most suitable for the Mexican tropic and what proportion of European breed is optimum for reproduction. Objective: To assess the effect of the proportion of Bos taurus (Bt) genes on reproductive performance of Holstein×Zebu (HZ) and Brown Swiss×Zebu (BZ) cows, and compare reproductive performance of these genotypes in a dual-purpose production system. Methods: Cows were maintained in a rotational grazing system on African star grass (Cynodon plectostachyus) in Veracruz, Mexico. Cows were milked twice daily. Calves were kept tied to the side of their dams while the cows were milked. Results: The percentage of Bt genes did not affect (p>0.05) fertility traits (age at first calving, days to first service after calving, services per conception, conception rate at first service, days open until conception, gestation length, and calving interval) of BZ cows. In contrast, HZ cows with less than 75% Holstein (H) genes were 0.3 years younger (p

En un diseño en bloques al azar con arreglo factorial 2 x 2, se estudió la calidad, desarrollo y acumulación de biomasa del pasto Cenchrus purpureus vc. CT-115. Los tratamientos consistieron en aplicación o no de riego durante el periodo seco, con un corte a 56 y 98 días. Se midieron el largo del tallo (cm), largo de hoja (cm), largo y grosor del segundo entrenudo (cm) y los rendimientos tMSha -1 totales, y de hojas y tallos, así como los porcentajes de PC (proteína cruda), FDA (fibra detergente ácido), FDN (fibra detergente neutro) y lignina en hoja. No se encontraron interacciones entre edad y riego para ninguna de las variables. El rendimiento de hojas, tallos y total fue mayor (P = 0.0001) cuando se aplicó riego y se cortó a los 98 días. Los indicadores: largo del tallo y hojas, grosor del tallo y largo de los entrenudos, fueron mejores cuando se aplicó riego. La PC en hoja fue mayor (P = 0.0007) a los 56 días con 11.45% y de 8.30% a los 98 días. La PC fue mayor (P= 0.0064) con riego 11.05% y de 8.70% sin riego. Se concluye que los incrementos en producción de MS total (tMSha -1 ) y la calidad de la biomasa indican la posibilidad de acortar los tiempos de reposo e incrementar la capacidad productiva de sistemas con bancos de biomasa de Cuba CT-115 cuando se aplica riego.

This work focuses on the study of the corona discharge breakdown in groove gap waveguides (GGWs) and inductive bandpass filters (BPFs) based on this technology. With the main aim of improving the peak power handling capability (PPHC), the location of the maximum normalized electric field strength $(|{\hat {E}}_{\text {MAX}}|)$ as a function of the geometrical parameters is analyzed. First, the research deals with wave-guiding structures, comparing the distribution of the transverse electric TE10-like mode of a GGW to that of an equivalent rectangular waveguide (RW). Next, a design strategy based on the adjustment of the geometrical dimensions of the bed of nails is proposed, thus achieving a considerable reduction of $|{\hat {E}}_{\text {MAX}}|$ . The second part of this paper aims for vertically polarized GGW BPFs, where the inductive irises become the most critical part of the component. By a simple modification of their dimensions, a second design criterion is suggested for improving the PPHC. Finally, several Ku-band BPFs centered at 14 GHz and 16 GHz have been manufactured and experimentally verified at the European High-Power Radiofrequency Space Laboratory. This measurement campaign shows peak power thresholds up to 1.09 kW and 3.59 kW at 600 mbar for the non- and full-optimized GGW BPFs, respectively, thereby demonstrating a PPHC enhancement up to 5.16 dB in the high-pressure range when both strategies, proposed in this work, are used.

The space industry is seeking new solutions for the development of lightweight, inexpensive and easy-to-manufacture on-board communication payload devices. One of the proposed technologies is additive manufacturing (AM) of polymeric materials that are subsequently metallized. The devices developed using this technique must be operational in the particular space environment conditions. In this work we study the integrity of filters made by additive manufacturing against the extreme conditions of mechanical stress, temperature and power management as described in the standard of the European Space Agency (ESA) for satellite payload. To carry out this qualification for space, two types of X-band filters with identical frequency responses have been designed and manufactured: a classic H-plane waveguide cavities filter, and three filters on surface-mount technology (SMT). Two of the SMT filters are low height rectangular cavities filters, while the third one is a high circular cavities filter. This selection was intended to verify that the AM technique offered good results regardless of the devices topology. Two mechanical vibration tests were performed: sinusoidal sweep and random vibration. These tests emulate the transport and launching conditions of the satellite payload. Furthermore, it was measured the mechanical natural frequency of the filters, and its variation after being exposed to the tests in order to evaluate their physical integrity. The thermal analysis was performed emulating the temperature profile experienced by the satellite payload during working conditions. Then, the power handling tests were carried out. The secondary electron emission yield of the material (metallized polymer) was firstly measured. The power levels, location and frequency at which a multipactor discharge would occur were analyzed for both, low-height and standard-height, filters. Finally, both filters were subjected to those power levels, under high vacuum conditions, to check if the said multipactor discharges occurred. The mechanical stress and temperature tests prove that the developed filters can survive the hard launching and operation conditions of commercial satellite payloads. The multipactor tests report the high power levels that the devices can handle without risk of radiofrequency (RF) breakage. All these tests allow to fully qualify the proposed manufacturing technique for spatial applications.

The objective of this paper is to show how inductive quadruplets with diagonal cross-couplings can be used as building blocks for filters in rectangular waveguide. Starting with the coupling matrix synthesis, we show how very general transfer functions can be easily implemented with a very simple step-by-step procedure. In addition to coupling matrix theory, we also describe distributed networks that can be effectively used to carry out the transition from coupling matrix descriptions to actual waveguide structures. Several filter design examples are also described in detail. Finally, measured results are also discussed showing excellent agreement with simulations, thereby fully validating both the new family of filter structures and the related design procedures.

Multipactor has become a keylimiting factor of the final performance of satellite communication systems, due to the increase in power levels and/or operating frequency bands. As a result, the critical components of these systems must meet demanding multipactor specifications which should be considered during the design process. This paper describes the different techniques available to predict the multipactor threshold power for radio frequency (RF) and microwave passive hardware under continuous wave (CW) excitation, from cumbersome particle simulations to fast approximate methods based on circuit models. All these techniques have been described and compared together for the first time, including also a detailed description of the configuration issues of commercial particle simulators required to obtain accurate multipactor threshold predictions. The techniques are applied to both wideband and narrowband application examples. The predictions have been compared with measured thresholds of manufactured samples obtained with a novel multipactor test bed, thus allowing to highlight the advantages and limitations of each technique and particle simulator. From this paper, it will be possible to choose the most suitable procedure (and an appropriate simulator, if needed) to obtain multipactor threshold prediction of passive hardware.

Empty Substrate Integrated Waveguide (ESIW) technology preserves the many advantages of the Substrate Integrated Waveguide (SIW) such as low cost, low profile, and easy integration with Printed Circuit Boards (PCBs). Moreover, it has additional advantages due to the avoidance of dielectric filling: lower insertion losses and resonators with higher quality factor. In order to connect the ESIW line to classical planar lines, the design of transitions becomes specially important. Due to this, some microstrip-to-ESIW transitions have been published in recent years. Problems of these transitions are usually the complexity of the manufacturing process or increased radiation losses. Knowing the aforementioned disadvantages of the published solutions, in this paper, the transition with an expanded ESIW section has been improved, by adding an easy-to-manufacture dielectric taper that minimizes the undesired radiation losses. Additionally, the new proposed transition can be mechanized easier than previous solutions based on sharp tapers. Moreover, the slight overlap between the microstrip line and the upper ESIW metal cover has been avoided, thus enhancing the return losses of the proposed transition. To validate the proposed transition, two back-to-back prototypes have been manufactured both in Ku- and Ka-band, obtaining insertion losses lower than 0.31 dB and return losses higher than 20.8 dB in Ku-band, and insertion losses lower than 1.36 dB and return losses higher than 14.75 dB in Ka-band.

The advantages of the Substrate-Integrated Waveguide (SIW) in terms of low profile, integration with Printed Circuit Board (PCB) and low cost are maintained by the Empty Substrate-Integrated Waveguide (ESIW). Moreover, as the dielectric fill is avoided, other advantages are also added: resonators with higher quality factor and lower insertion losses. Since 2014, when it was proposed, several devices for X-band to Ka-band applications have been accurately designed and manufactured. In this way, transitions are one of the most important components, as they allow the connection between the ESIW and other planar transmision lines such as microstrip. To accomplish this aim, different transitions have been proposed in the literature: based on sharp dielectric tapers combining metallized and non-metallized parts, which increases the manufacture complexity; with a broadened ESIW section, that is less complex at the cost of increasing reflection and radiation losses due to the abrupt discontinuity; based on tapered artificial dielectric slab matrix, more difficult to mechanize; using a tapered microstrip transition, with high radiation losses; and even transitions for multilayer devices. Among all the transitions, the most versatile one is the through-wire transition, as microstrip and ESIW can be implemented in different layers and allows any feeding angle between the microstrip line and the ESIW. In this paper the through-wire transition has been properly validated at Ku- and Ka-bands. Moreover, a back-to-back transition has been accurately manufactured in Ka-band with measured insertion losses lower than 3.7 dB and return losses higher that 11.7 dB, concluding that the transition is not frequency dependent.

Rationale & Objective: Venglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in mouse models of autosomal dominant polycystic kidney disease (ADPKD). STAGED-PKD aims to determine the safety and efficacy of venglustat and was designed using patient enrichment for progression to end-stage kidney disease and modeling from prior ADPKD trials. Study Design: STAGED-PKD is a 2-stage, international, double-blind, randomized, placebo-controlled trial in adults with ADPKD (Mayo Class 1C-1E) and estimated glomerular filtration rate (eGFR) 45-

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes shared by many other diseases. Dysfunction of the polycystins, encoded by the PKD genes, is closely associated with disruption of calcium and upregulation of cyclic AMP and protein kinase A (PKA) signaling, affecting most downstream regulatory, signaling, and pathophysiologic pathways altered in this disease. Interventions acting on G protein coupled receptors to inhibit of 3′,5′-cyclic adenosine monophosphate (cAMP) production have been effective in preclinical trials and have led to the first approved treatment for ADPKD. However, completely blocking cAMP mediated PKA activation is not feasible and PKA activation independently from cAMP can also occur in ADPKD. Therefore, targeting the cAMP/PKA/CREB pathway beyond cAMP production makes sense. Redundancy of mechanisms, numerous positive and negative feedback loops, and possibly counteracting effects may limit the effectiveness of targeting downstream pathways. Nevertheless, interventions targeting important regulatory, signaling and pathophysiologic pathways downstream from cAMP/PKA activation may provide additive or synergistic value and build on a strategy that has already had success. The purpose of this manuscript is to review the role of cAMP and PKA signaling and their multiple downstream pathways as potential targets for emergent therapies for ADPKD.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) causes kidney failure typically in adulthood, but the disease starts in utero. Copeptin, epidermal growth factor (EGF), and monocyte chemoattractant protein-1 (MCP-1) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is suggested from rodent models. Methods: In a cross-sectional study, plasma copeptin, urinary EGF, and urinary MCP-1 were evaluated in a pediatric ADPKD cohort and compared with age-, sex-, and body mass index (BMI)-matched healthy controls. MCP-1 was studied in mouse collecting duct cells, human proximal tubular cells, and fetal kidney tissue. Results: Fifty-three genotyped ADPKD patients and 53 controls were included. The mean (SD) age was 10.4 (5.9) versus 10.5 (6.1) years (P = 0.543), and the estimated glomerular filtration rate (eGFR) was 122.7 (39.8) versus 114.5 (23.1) ml/min per 1.73 m2 (P = 0.177) in patients versus controls, respectively. Plasma copeptin and EGF secretion were comparable between groups. The median (interquartile range) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD patients (185.4 [213.8]) compared with controls (154.7 [98.0], P = 0.010). Human proximal tubular cells with a heterozygous PKD1 mutation and mouse collecting duct cells with a PKD1 knockout exhibited increased MCP-1 secretion. Human fetal ADPKD kidneys displayed prominent MCP-1 immunoreactivity and M2 macrophage infiltration. Conclusion: An increase in tubular MCP-1 secretion is an early event in ADPKD. MCP-1 is an early disease severity marker and a potential treatment target.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and a loss of functioning renal mass, but a decline in glomerular filtration rate (GFR) and onset of end-stage renal disease (ESRD) occur late in the disease course. There is therefore a great need for early prognostic biomarkers in this disorder. Methods: We measured baseline serum fibroblast growth factor 23 (FGF23) levels in 192 patients with ADPKD from the Consortium for Radiologic Imaging Studies of PKD (CRISP) cohort that were followed for a median of 13 years and tested the association between FGF23 levels and change over time in height-adjusted total kidney volume (htTKV), GFR, and time to the composite endpoints of ESRD, death, and doubling of serum creatinine. Results: Patients in the highest quartile for baseline FGF23 level had a higher rate of increase in htTKV (0.95% per year, P = 0.0016), and faster rate of decline in GFR (difference of −1.03 ml/min/1.73 m2 per year, P = 0.005) compared with the lowest quartile, after adjusting for other covariates, including htTKV and genotype. The highest quartile of FGF23 was also associated with a substantial increase in risk for the composite endpoint of ESRD, death, or doubling of serum creatinine (hazard ratio [HR] of 2.45 in the fully adjusted model, P = 0.03). Conclusion: FGF23 is a prognostic biomarker for disease progression and clinically important outcomes in ADPKD, and has additive value to established imaging and genetic biomarkers.

Introduction: In pivotal trials of patients with autosomal dominant polycystic kidney disease at risk of rapid progression, tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in early-to-moderate (TEMPO 3:4 [NCT00428948]) and moderate- to late-stage (REPRISE [NCT02160145]) chronic kidney disease (CKD). Discontinuation was less frequent in REPRISE (15.0%) than TEMPO 3:4 (23.0%), given that in REPRISE, only subjects who tolerated tolvaptan 60/30 mg daily initiated the double-blind phase. We evaluated whether the greater treatment effect in REPRISE was attributable to different completion rates. Methods: We conducted post hoc analyses of TEMPO 3:4 and REPRISE completers, defined as subjects who took trial drug to the end of the treatment period in TEMPO 3:4 (3 years) or REPRISE (1 year). Efficacy (rate of change in eGFR for tolvaptan vs. placebo) was analyzed as in each trial. Subjects from TEMPO 3:4 and REPRISE were also matched by propensity score for age, gender, and baseline eGFR to explore potential additional determinants of treatment effect. Results: The annualized tolvaptan treatment effect in TEMPO 3:4 completers (difference vs. placebo of 0.98 ml/min per 1.73 m2/y) and REPRISE completers (difference of 1.23) was similar to that of the respective total trial populations (TEMPO 3:4: 0.94; REPRISE: 1.27). The treatment effect of tolvaptan was also similar between matched subjects. Conclusion: Greater treatment completion rate did not drive greater treatment effect in REPRISE. The more advanced CKD of REPRISE subjects may be more relevant. More rapid decline in kidney function in later-stage CKD enabled the effects of tolvaptan to be more easily discerned.

The Empty Substrate Integrated Waveguides (ESIW) maintain the advantages of the Substrate Integrated waveguide (SIW) (i.e. low-volume, low profile, lightweight, easy manufacturing, and integration in a planar circuit board), and present lower losses and higher quality factors in resonators due to the propagation of the fields through air, instead of through lossy dielectric as in SIW. The operational (monomode) bandwidth of the ESIW can be increased with the Single Ridge ESIW (SRESIW). However, the bandwidth can be further increased with the Double Ridge ESIW (DRESIW). In this paper, a brief study of possible DRESIW geometries has been performed, and two transitions from microstrip line (MS) to DRESIW with a dielectric taper geometry based on different equations are proposed. The new wideband transitions present simulated return losses in back-to-back configurations greater than 20 dB in more than a 95% fractional bandwidth. The transition that presents a better compromise between return losses, bandwidth and ease of fabrication is manufactured. The measured return and insertion losses are better than 19.7 dB and 1.5 dB, respectively, in a 96.4% fractional bandwidth.

This paper provides a new theoretical model for the characterization of passive intermodulation behaviour when non-contributing carriers (i.e., carriers which do not directly affect the particular non-linear contribution under analysis) are added to classical two or three carriers scenarios. According to traditional models, the power of a particular passive intermodulation frequency term is only related to the contributing carriers which combines in non-linear way to generate this term, thus the presence of additional (i.e., non-contributing) carriers should not affect to the predicted power of such an intermodulation product. However, recent laboratory tests reveal that non-contributing carriers do reduce the power of unrelated passive intermodulation terms. A heuristic model is proposed in this work to explain this effect, which shows a good matching with measured results already published in the technical literature. The study is focused in third order non-linear contributions, as being the most critical in practical applications.

Rationale & Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts’ presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease. Study Design: Case series. Setting & Participants: Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded. Results: Twelve patients with SLC34A3 pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease. Limitations: Retrospective study, possible selection bias, single-center experience. Conclusions: A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in SLC34A3 favor cyst formation.

The objective of this paper is to describe the design of an innovative and low-cost diplexer for Ka-band multi-beam satellite applications. The device is based on the use of two quadruplets to implement a number of transmission zeros (TZs) thus obtaining high-selectivity quasi-elliptic transfer functions. The resulting diplexer structure is particularly flexible in terms of layout, does not require tuning and has an excellent high-power behavior. In addition to theory, we compare the results of our simulations with the measurements obtained with a manufactured breadboard. The comparison shows excellent agreement thereby fully validating both the design procedure, and the new diplexer structure.

Substrate Integrated (SI) technologies, either completely or partially filled with dielectric, as well as completely empty (i.e. without any dielectric material), have been object of intense research in the last years. Their performance in terms of losses, cost and size are mid-way between those of classical planar lines and rectangular waveguides. Many communication devices have already been successfully designed, manufactured and measured in all these SI technologies. But these measurements are mostly done at room temperature under atmospheric pressure conditions. However, the good results (in terms of low loss, profile and cost) of these novel technologies, especially the completely empty versions, close to the performance of the rectangular waveguide, make them a very good alternative for being used in small satellite payloads. Up to now, few attention has been given to the thermal analysis of these SI technologies, still missing a complete comparative study of these effects under both, atmospheric pressure and vacuum conditions. In this work the same filter is implemented on four different SI technologies (including completely and partially filled with dielectric, as well as empty -no dielectric- versions). The four filters are designed, manufactured, and measured at different temperatures according to the thermal testing standards for space applications. The thermal study is performed under atmospheric pressure conditions and, for the first time, under high vacuum conditions. Finally, a comparison with all previous available thermal studies (all of them performed at atmospheric pressure levels) is included.

Objective: To describe first episodes of bacterial cholangitis complicating autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD) and to identify risk factors for cholangitis episodes among patients with ADPKD-associated polycystic liver disease (PLD). Patients and Methods: We searched the electronic medical records at our tertiary referral center for episodes of cholangitis in patients with ADPKD or ADPLD from January 1, 1996, through June 30, 2017. Cases were categorized as suspected or definite cholangitis by expert review. Clinical, laboratory, and radiologic data were manually abstracted. A nested case-control study was conducted to investigate risk factors for cholangitis in patients with ADPKD. Results: We identified 29 cases of definite or suspected cholangitis complicating PLD (24 with ADPKD-associated PLD and 5 with ADPLD). Among patients with definite cholangitis in ADPKD-associated PLD (n=19) vs ADPLD (n=4), the mean ± SD age was 62.4±12.2 vs 55.1±8.6 years, and 9 (47.4%) vs 0 (0%), respectively, were male. The odds of gallstones (odds ratio [OR], 21.6; 95% CI, 3.17-927; P

The use of singlets, cascaded singlets, and doublets in a coaxial substrate integrated waveguide (SIW) technology is proposed in this paper, with the aim of implementing low-loss filters with very compact size and highly selective symmetric, asymmetric as well as dual-band responses. Singlets based on coaxial SIW resonator structures with source-load coupling are presented and studied. Then, different filter examples based on N cascaded singlets are designed, fabricated, and measured at 7.5 GHz, with up to N transmission zeros that can be easily located below and above the passband. Moreover, the application of doublets based on a dual-mode coaxial SIW resonator with source-load coupling for achieving extremely compact dual-band filters is presented, and two examples with different bandwidth configuration for each channel are designed, demonstrating the flexibility of the proposed coaxial SIW structure. The obtained experimental results of the differently implemented filters show a good agreement with simulations, thus confirming the interesting potential application of these structures for the design of very compact devices with advanced filtering responses.

Recently, Empty Substrate Integrated Waveguide (ESIW) technology was proposed for embedding empty waveguides into planar substrates in order to improve their performance. A low-loss and narrow-band transition from microstrip to an increased height ESIW with 4 layers was presented in a previous work, and used to implement a very high-quality factor bandpass filter at Q-band. With such a narrow-band transition, based on a quarter-wavelength transformer, a very narrow-band filter response with resonators having a quality factor of 1000 was achieved. In this paper, in order to overcome the narrow-band and the 4-layers output restrictions, and extend the practical use of such increased height ESIWs beyond narrow-band filters, we present a novel wideband transition from microstrip to an increased height ESIW with an arbitrary number of layers. A full suite of wideband transitions to increased height ESIWs, built with different number of substrate layers ranging from 3 to 8, has been designed in this work to operate at Ka-band, though they can be easily transferred to other bands if the dimensions of the transition are properly scaled. To illustrate this, the original Ka-band transitions have been mapped to Ku-band, with excellent results. In order to test the proposed design method, a prototype of a 4-layer structure has been fabricated at Ka-band, achieving a good performance in the whole useful bandwidth of the ESIW.

En un diseño en bloques al azar con arreglo factorial 2 x 2, se estudió la calidad, desarrollo y acumulación de biomasa del pasto Cenchrus purpureus vc. CT-115. Los tratamientos consistieron en aplicación o no de riego durante el periodo seco, con un corte a 56 y 98 días. Se midieron el largo del tallo (cm), largo de hoja (cm), largo y grosor del segundo entrenudo (cm) y los rendimientos tMSha-1 totales, y de hojas y tallos, así como los porcentajes de PC (proteína cruda), FDA (fibra detergente ácido), FDN (fibra detergente neutro) y lignina en hoja. No se encontraron interacciones entre edad y riego para ninguna de las variables. El rendimiento de hojas, tallos y total fue mayor (P = 0.0001) cuando se aplicó riego y se cortó a los 98 días. Los indicadores: largo del tallo y hojas, grosor del tallo y largo de los entrenudos, fueron mejores cuando se aplicó riego. La PC en hoja fue mayor (P = 0.0007) a los 56 días con 11.45 % y de 8.30 % a los 98 días. La PC fue mayor (P = 0.0064) con riego 11.05 % y de 8.70 % sin riego. Se concluye que los incrementos en producción de MS total (tMSha-1) y la calidad de la biomasa indican la posibilidad de acortar los tiempos de reposo e incrementar la capacidad productiva de sistemas con bancos de biomasa de Cuba CT-115 cuando se aplica riego. Palabras clave Rendimiento, periodo seco, tallo, hoja.

Abstract Background Caffeine has been proposed, based on in vitro cultured cell studies, to accelerate progression of autosomal dominant polycystic kidney disease (ADPKD) by increasing kidney size. Since ADPKD patients are advised to minimize caffeine intake, we investigated the effect of caffeine on disease progression in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), a prospective, observational cohort study. Methods Our study included 239 patients (mean age = 32.3 ± 8.9 ys; 188 caffeine consumers) with a median follow-up time of 12.5 years. Caffeine intake reported at baseline was dichotomized (any vs. none). Linear mixed models, unadjusted and adjusted for age, race, sex, BMI, smoking, hypertension, genetics and time, were used to model height-adjusted total kidney volume (htTKV) and iothalamate clearance (mGFR). Cox proportional hazards models and Kaplan-Meier plots examined the effect of caffeine on time to ESRD or death. Results Caffeine-by-time was statistically significant when modeling ln(htTKV) in unadjusted and adjusted models (p 0.05). Moreover the results were similar when outcomes were modeled as a function of caffeine dose. Conclusion We conclude that caffeine does not have a significant detrimental effect on disease progression in ADPKD.

El presente texto busca mostrar las relaciones de transtextualidad que se dan entre la primera obra de Gabriela Mistral, Desolación (1922), y algunos temas recurrentes de los “poemas mayores” de san Juan de la Cruz, como la concepción de la muerte como camino hacia la vida, el dolor y la consideración de la naturaleza como reflejo de Dios, explicitando, para ello, las fuentes de dicha transtextualidad.

Background & Aims: Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, the frequency of truncating mutations to ADPLD genes in large, population sequencing databases is 1:496. With the increasing use of abdominal imaging, incidental detection of hepatic cysts and ADPLD has become more frequent. The present study was performed to ascertain the incidence and point prevalence of ADPLD in Olmsted County, MN, USA, and how these are impacted by the increasing utilisation of abdominal imaging. Methods: The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center were searched to identify all subjects meeting diagnostic criteria for definite, likely, or possible ADPLD. Annual incidence rates were calculated using incident cases during 1980–2016 as numerator, and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator, and age- and sex-specific estimates of the population of Olmsted County on 1 January 2010 as denominator. Results: The incidence rate and point prevalence of combined definite and likely ADPLD were 1.01 per 100,000 person-years and 9.5 per 100,000 population, respectively. Only 15 of 35 definite and likely incident ADPLD cases had received a diagnostic code, and only 8 had clinically significant hepatomegaly. The incidence rates were much higher when adding possible cases, mainly identified through radiology databases, particularly in recent years and in older patients because of the increased utilisation of imaging studies. Conclusions: Clinically significant isolated ADPLD is a rare disease with a prevalence

A partir de análise da argumentação habermasiana realizada em sua obra “Conhecimento e Interesse” original de 1968, a qual trabalhamos a partir da tradução de 1987; e ancorados nos trabalhos dos filósofos brasileiros Durão, publicado em seu livro “A crítica de Habermas à dedução transcendental de Kant” de 1996 e Hansen, em seu artigo publicado na Revista Crítica, intitulado “Os riscos da crítica da sociedade” de 1998, refletimos, nesse artigo, sobre como Habermas resgata a Teoria do Conhecimento da maneira desvirtuada que a legou o positivismo comteano, perpassando por Freud e Marx para recuperá-la como uma Teoria Crítica da Sociedade. E, apresentamos o advento da Era da Informação e as facilidades de comunicação que a acompanham, para apresentar o modelo da Educação à Distância como uma forma eficaz de ampliar o alcance da Crítica Social como autorreflexão que torna o conhecimento um instrumento crítico não só do indivíduo, mas também da sociedade.

Background: Knowledge of genetic correlations and the economics of traits are essential to decide which traits should be used as selection criteria. Objective: To estimate heritabilities and genetic, environmental, and phenotypic correlations, and direct (DRS) and correlated (CRS) responses to selection by scrotal circumference (SC), frame score (FS), and yearling weight (YW) of Mexican Charolais (CH), and Charbray (CB) Young bulls. Methods: Actual SC, height and YW records (10,078 for CH, and 500 for CB) were adjusted to 365 d. The 0.0505 adjustment factor recommended by the Beef Improvement Federation was used to obtain the 365-d adjusted SC for both breeds. Height and age records were used to obtain FS. Data were analyzed using a three-trait animal model. The animal model for each trait included bull breed, contemporary group (groups of young bulls born in the same herd, year, and season of the year), and age of dam as a linear covariate as fixed effects, and direct additive genetic and residual as random effects. Results: Heritability estimates for SC, FS and YW were 0.21 ± 0.04, 0.25 ± 0.04, and 0.29 ± 0.04, respectively. The genetic correlation between YW with SC was 0.37 ± 0.16, and between YW with FS was 0.42 ± 0.16. The estimate of genetic correlation between SC and FS was low and positive (0.15 ± 0.14). The DRS was 0.38 cm, 0.18 units, and 8.30 kg for SC, FS and YW. The CRS was 0.16 cm, and 0.08 units for SC and FS from indirect selection on YW. Conclusions: Direct selection for YW is expected to be effective. Indirect selection for SC and FS based on YW would not be expected to be as effective as direct selection for improving SC and FS.

Introduction: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. Methods: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin−angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR) > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI) measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. Results: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both). Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively). Conclusion: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI. Keywords: autosomal dominant polycystic kidney disease, hypertension, left ventricular hypertrophy, left ventricular mass index

Con el objetivo de estimar las varianzas y covarianzas genéticas entre producción total de leche por lactación y crecimiento corporal en una población multirracial de bovinos de doble propósito en el trópico de México, se estimaron las varianzas y covarianzas genéticas entre la producción total de leche durante la primera (PTL1L), la segunda (PTL2L) y la tercera lactaciones (PTL3L), y las varianzas y covarianzas genéticas entre PTL1L con peso al nacimiento (PN) y los pesos ajustados a los 205 (P205) y 365 (P365) días de edad. Se utilizaron 1,349 registros de lactaciones de hembras de cruzas de razas cebuinas (CE) con Holstein (HS) [558], con Suizo Pardo (SP) [444] y con Simmental (SM) [357]. Se presentan las heredabilidades estimadas en ambos análisis. Las correlaciones genéticas encontradas en el primer análisis fueron 0.77 (± 0.16) entre PTL1L y PTL2L, 0.47 (± 0.25) entre PTL1L y PTL3L, y 0.73 (± 0.21) entre PTL2L y PTL3L. Las correlaciones genéticas encontradas en el segundo análisis fueron 0.10 (± 0.35) entre PTL1L y PN, 0.20 (± 0.25) entre PTL1L y P205 y 0.21 (± 0.32) entre PTL1L y P365. Se concluye que las correlaciones genéticas son positivas entre las tres primeras lactaciones y se sugiere una correlación positiva entre la primera lactación y características de crecimiento corporal, lo cual hace factible el planteamiento de programas de mejoramiento genético que tomen en cuenta ambas características de manera simultánea.

In this work, a novel rotation approach for the antenna elements of a linear phased array is presented. The proposed method improves by up to 14 dB the cross-polarization level within the main beam by performing a sequential 90° rotation of the identical array elements, and achieving measured cross-polarization suppressions of 40 dB. This configuration is validated by means of simulation and measurements of a manufactured linear array of five dual-polarized cavity-box aperture coupled stacked patch antennas operating in L-Band, and considering both uniform amplitude and phase distribution and beamforming with amplitude tapering. The analysis is further extended by applying and comparing the proposed design with the 180° rotation and non-rotation topologies. This technique is expected to be used for the next generation L-Band Airborne Synthetic Aperture Radar Sensor of the German Aerospace Center (DLR).

Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). Experimental evidence suggests an important role of the polycystins in cardiac development and myocardial function. To determine whether ADPKD may predispose to the development of cardiomyopathy, we have evaluated the coexistence of diagnoses of ADPKD and primary cardiomyopathy in our patients. Methods: Clinical data were retrieved from medical records for patients with a coexisting diagnosis of ADPKD and cardiomyopathies evaluated at the Mayo Clinic (1984–2015). Results: Among the 58 of 667 patients with available echocardiography data, 39 (5.8%) had idiopathic dilated cardiomyopathy (IDCM), 17 (2.5%) had hypertrophic obstructive cardiomyopathy, and 2 (0.3%) had left ventricular noncompaction. Genetic data were available for 19, 8, and 2 cases of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction, respectively. PKD1 mutations were detected in 42.1%, 62.5%, and 100% of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction cases, respectively. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (15%). In at least 1 patient from 3 IDMC families and 1 patient from a hypertrophic obstructive cardiomyopathy family, the cardiomyopathy did not segregate with ADPKD, suggesting that the PKD mutations may be predisposing factors rather than solely responsible for the development of cardiomyopathy. Discussion: Coexistence of ADPKD and cardiomyopathy in our tertiary referral center cohort appears to be higher than expected by chance. We suggest that PKD1 and PKD2 mutations may predispose to primary cardiomyopathies and that genetic interactions may account for the observed coexistence of ADPKD and cardiomyopathies.

Total kidney volume (TKV) is a promising imaging biomarker for tracking and predicting the natural history of patients with autosomal dominant polycystic kidney disease. Methods: A drug development tool was developed by linking longitudinal TKV measurements to the probability of a 30% decline of estimated glomerular filtration rate (eGFR) or end-stage renal disease. Drug development tools were developed based on observational data collected over multiple decades for an eGFR decline and end-stage renal disease in 641 and 866 patients with autosomal dominant polycystic kidney disease, respectively. Results: The statistical association between predicted TKV at the time of a 30% decline of eGFR and that at the time of end-stage renal disease were both highly significant (P < 0.0001). The drug development tool was applied to demonstrate the utility of trial enrichment according to prespecified baseline TKV, age, and eGFR as enrollment criteria in hypothetical clinical trials. Patients with larger TKV (≥1000 ml) displayed steeper slopes of hazard, which translated into a higher risk of a 30% decline of eGFR within each baseline age (< or ≥40 years) or baseline eGFR (< or ≥50 ml/min per 1.73 m2) subgroups. Discussion: These results suggest that, when eGFR is preserved, patients with larger TKV are more likely to progress to a 30% decline of eGFR within the course of a clinical trial, whereas eGFR and age displayed limited predictive value of disease progression in early disease. Pharmaceutical sponsors and academic investigators are encouraged to prospectively employ the above drug development tool to optimize trial designs in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30% decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available. Methods: Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30% decline in eGFR or ESRD. Results: TKV was the most important prognostic term for 30% decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m2), the adjusted hazard ratios for a 30% decline in eGFR were 1.86 (95% CI, 1.65–2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95% CI, 2.22–3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95% CI, 1.49–1.99) and 2.36 (95% CI, 1.88–2.97), respectively. Discussion: The capability to predict 30% decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.

Patients with slowly progressive autosomal dominant polycystic kidney disease (ADPKD) are unlikely to experience outcomes during randomized controlled trials (RCTs). An image classification of ADPKD into typical (diffuse cyst distribution) class 1A to E (by age- and height-adjusted total kidney volume [TKV]) and atypical (asymmetric cyst distribution) class 2 was proposed for prognostic enrichment design, recommending inclusion of only classes 1C to 1E in RCTs. Methods: A post hoc exploratory analysis was conducted of the TEMPO 3:4 Trial, a prospective, randomized, double-blinded, controlled clinical trial in adult subjects with ADPKD, an estimated creatinine clearance >60 ml/min and total kidney volume >750 ml. Results: Due to the entry criteria, the study population of TEMPO 3:4 was enriched for classes 1C-E (89.5 % of 1436 patients with baseline magnetic resonance images) compared to unselected populations (e.g., 60.5% of 590 Mayo Clinic patients). The effects of tolvaptan on TKV and eGFR slopes were greater in classes 1C to E than in 1B. In TEMPO 3:4, tolvaptan reduced TKV and eGFR slopes from 5.51% to 2.80% per year and from −3.70 to −2.78 ml/min/1.73 m2 per year, and lowered the risk for a composite endpoint of clinical progression events (hazard ratio = 0.87). Restricting enrollment to classes 1C to E would have reduced TKV and eGFR slopes from 5.78% to 2.91% per year and from −3.93 to −2.82 ml/min/1.73 m2 per year, and the risk of the composite endpoint (hazard ratio = 0.84, P = 0.003), with 10.5% fewer patients. Discussion: Prognostic enrichment strategies such as the entry criteria used for TEMPO 3:4 or preferably the proposed image classification should be used in RCTs for ADPKD to increase power and to reduce cost.

Introducción: El objetivo de este trabajo fue describir las propiedades psicométricas preliminares de la “Escala de autoeficacia para hábitos alimentarios”. Material y métodos: Participaron en un ensayo clínico aleatorizado para la modificación del estilo de vida 135 sujetos con síndrome metabólico, divididos en dos grupos (grupo control y grupo experimental), con un seguimiento de 18 meses. La evaluación incluyó datos antropométricos, clínicos, psicológicos y de estilo de vida. Para la validez y fiabilidad se realizó análisis factorial, de la consistencia interna, estabilidad temporal, sensibilidad al cambio y validez concurrente. Resultados: La solución de 2 factores explica el 60,97% de la varianza común. La consistencia interna para la puntuación total fue de 0,971 - alfa de Cronbach. En cuanto a la estabilidad temporal, no se observó ningún cambio en el grupo control. Con respecto a la sensibilidad al cambio, el grupo experimental presentó mayor autoeficacia a lo largo del seguimiento. Conclusiones: Los resultados preliminares mostraron niveles adecuados de validez y fiabilidad, demostrando ser una escala útil para evaluar la autoeficacia relacionada a la alimentación.