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Objective: To evaluate the clinical outcomes of pediatric patients implanted a novel 4.5 mm wide laser ablated titanium bone anchored implant system and to evaluate the implant stability over the first 12-month period. Study Design: A prospective, single-subject, repeated measure, cohort study. Participants served as their own controls. Setting: Community and tertiary referral hospital pediatric assessment center. Patients: A total of 115 consecutive pediatric patients aged 4 to 15 years were implanted with 176 laser ablated titanium bone anchored implants from January 2016 to January 2019. Main Outcome Measure: Clinical outcomes, implant failure rates, and post implantation implant stability quotient (ISQ) scores were studied over the first 12-month period. Data were analyzed for statistical significance through mixed effect modeling, with the significance level p = 0.01. Results: A median 12-month survival of 96.6% was observed. Six implants (3.5%) were lost in total, one of these (0.6%) was lost due to trauma. Adverse skin reactions (Holgers grade 2–4) were observed in 4.4% of all postoperative visits, occurring in 22 individuals (19.1%). Neither the ISQ high (ISQH) nor ISQ low (ISQL) values increased significantly between the stage 1 and 2 surgeries. In contrast, the ISQ results, irrespective of abutment size, demonstrated an increasing trend from 49.1 to 57 over the 12 months review period. A statistically significant change was only demonstrated from the 3 months follow up onwards. Conclusion: The use of 4.5 mm wide laser-ablated titanium bone anchored hearing implants resulted in superior survival rates and excellent clinical outcomes compared with previous implant systems.

Fixed-beam, high-gain antenna systems can be used for a finer partitioning of the currently used cell-sectoring. This partitioning has the benefit of reducing the number of users seen per antenna beam, which reduces interference. Furthermore, the high antenna gain allows for a high effective isotropic radiated power while keeping the transmit power low. In this paper, we study the performance of such a fixed-beam, high gain antenna system design for millimeter-wave mobile communications. The antenna system is designed to keep the inter-sector interference in a multi-site scenario low. The performance is analyzed for single- and multi-user environments. In single-input single-output mode, the 50th percentile of the signal-to-interference-plus-noise ratio lies between 12.5 dB to 39.7 dB if 3 to 0 interferers are present, respectively. For multiple-input multiple-output transmission using zero-forcing, the signal-to-interference-plus-noise ratio increases and the 50th percentile ranges from 36.1 dB to 43.3 dB if 3 to 0 interferes are present, respectively. By using maximum ratio transmission, the best performance is achieved with no interferers present, while a plunge in performance is observed with interferers. Furthermore, the study revealed that the narrow beam antenna system can also provide a clear signal separation for small spatial separations. In the given example, the signal-to-interference-plus-noise ratio is larger than 32.1 dB with 11 active antenna elements, where 2.8 meters separate the users. Hence, the paper shows that the cell-partitioning antenna systems provide coverage in the desired area while keeping the inter-sector interference low, and the considered transmission techniques can be used for situation optimized mobile communication links.

ispartof: Ieee Antennas And Wireless Propagation Letters vol:21 issue:9 pages:1-5 status: accepted

Heterogeneity in Parkinson’s disease (PD) presents a barrier to understanding disease mechanisms and developing new treatments. This challenge may be partially overcome by stratifying patients into clinically meaningful subtypes. A recent subtyping scheme classifies de novo PD patients into three subtypes: mild-motor predominant, intermediate, or diffuse-malignant, based on motor impairment, cognitive performance, REM-sleep behavior disorder, and autonomic function. We aimed to validate this approach in a large longitudinal cohort of early-stage PD (n=517). Furthermore, we assessed the influence of subtype on clinical motor phenotype and on one-year clinical disease progression. Diffuse-malignant patients (14%) differed from mild-motor predominant patients (48%) in three ways: involvement of more clinical domains, more diffuse hypokinetic-rigid symptoms (less lateralization, less hand/foot focality), and faster one-year progression. These findings extend the classification of diffuse-malignant and mild-motor predominant subtypes to early-stage PD and suggest that different pathophysiological mechanisms (focal versus diffuse cerebral propagation) may play a role.

There is an urgent need for new treatment options in metastatic drug-resistant prostate cancer. Combining immunotherapy with other targeted therapies may be an effective strategy for advanced prostate cancer. In the present study, we sought to investigate to enhance the efficacy of anti-CTLA-4 therapy against prostate cancer by the combination with STAT3 inhibition. Male C57BL6 mice were subcutaneously inoculated with the murine prostate cancer cell line RM-1. Tumor progression was monitored following treatment with vehicle, the small molecule STAT3 inhibitor GPB730, anti-CTLA-4 or GPB730 + anti-CTLA-4. Treatment with anti-CTLA-4 or anti-CTLA-4 + GPB730 significantly inhibited tumor growth and enhanced survival compared to vehicle. Combining anti-CTLA-4 treatment with GPB730 resulted in a significantly prolonged survival compared to anti-CTLA-4 alone. GPB730 significantly increased infiltration of CD45 + cells in tumors of anti-CTLA-4-treated mice compared to anti-CTLA-4 alone. The levels of tumor-infiltrating Tregs were significantly decreased and the CD8:Treg ratio significantly increased by GPB730 treatment in combination with anti-CTLA-4 compared to anti-CTLA-4 alone. Immunohistochemical analysis showed a significant increase in CD45-positive cells in anti-CTLA-4 and anti-CTLA-4 + GPB730-treated tumors compared to vehicle or GPB730 monotherapy. Plasma levels of IL10 were significantly increased by anti-CTLA-4 compared to vehicle but no increase was observed when combining anti-CTLA-4 with GPB730. In conclusion, STAT3 inhibition by GPB730 enhances the antitumoral activity of anti-CTLA-4 and decreases the intratumoral Treg frequency in a prostate cancer mouse model. These results support the combination of STAT3 inhibition with anti-CTLA-4 therapy to increase clinical responses in patients with prostate cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02915-6.

THG1L-associated autosomal recessive ataxia belongs to a group of disorders that occur due to abnormal mitochondrial tRNA modification. The product of THG1L is the tRNA-histidine guanylyltransferase 1-like enzyme that catalyzes the 3'-5"addition of guanine to the 5"-end of tRNA-histidine in the mitochondrion. To date, five individuals with homozygosity for p.(Val55Ala) in THG1L have been reported and presented with mild delays or normal development and cerebellar dysfunction. We present seven individuals with biallelic variants in THG1L. Three individuals were compound heterozygous for the p.(Cys51Trp) and p.(Val55Ala) variants and presented with profound developmental delays, microcephaly, intractable epilepsy, and cerebellar hypoplasia. Four siblings were homozygous for the p.(Val55Ala) variant and presented with cerebellar ataxia with cerebellar vermis hypoplasia, dysarthria, mild developmental delays, and normal/near-normal cognition. All seven patients were of Ashkenazi Jewish descent. Carrier rates for the two variants were calculated in a cohort of 26,731 Ashkenazi Jewish individuals tested by the Dor Yeshorim screening program. The p.(Cys51Trp) variant is novel and was found in 40 of the Ashkenazi Jewish individuals tested, with a carrier rate of 1 in 668 (0.15%). The p.(Val55Ala) variant was found in 229 of the Ashkenazi Jewish individuals tested, with a carrier rate of 1 in 117 (0.85%). The individuals with compound heterozygosity of the p.(Val55Ala) and p.(Cys51Trp) variants expand the phenotypic spectrum of THG1L-related disorders to include severe epileptic encephalopathy. The individuals with homozygosity of the p.(V55A) variant further establish the associated mild and slowly progressive or nonprogressive neurodevelopmental phenotype.

A new method is proposed to analyze antenna arrays including mutual coupling, which is based on the concept of multiple scattering and relates to the iterative Jacobi and Gauss-Seidel methods. The method employs sampled far-field data of an isolated element, which can be obtained by any full-wave simulator and consists of far fields for excitation at the antenna feed and for plane waves with different angles of incidence. Mutual interactions between the array elements are modeled by approximating the incident field as a single dual-polarized plane wave taken from the spherical wave expansion of the scattered field from any other element in the array. The accuracy and run-time performances of the method are evaluated mainly by comparing simulations for several array geometries to MoM-based full-wave solutions. The method is primarily intended as a tool for the fast sequential analysis of arrays while varying the array lattice, particularly in case of irregular or sparse lattices and complex elements requiring dense meshes in full-wave simulators. The applications of the method may thus range from the systematic analysis of mutual coupling to optimization and synthesis. The article is currently available in the early-access version on IEEE Xplore. ispartof: IEEE Transactions on Antennas and Propagation vol:69 issue:1 pages:206-218 status: accepted

Antenna and low-noise amplifier (LNA) co-design is a promising method for increasing the sensitivity of millimeter-wave (mmWave) receiver systems. Co-design involves several individual steps which usually do not intersect with each other in one design flow, but this method combines all of them together and allows to obtain mutual benefits for all components. This paper gives an overview of several different mmWave engineering tasks like antennas and monolithic microwave integrated circuit (MMIC) design together with RF interconnection solutions like wirebonding, flip-chip and packaging technology. The suggestion of the mmWave receiver co-design for achieving minimum noise figure at low costs is also provided.

Experimental data on pulmonary regurgitation has linked right ventricular longitudinal function to left ventricular filling pressure in animals with induced and treated pulmonary regurgitation but this relationship has not been investigated in patients with repaired Tetralogy of Fallot (rToF). The aim of this study was to determine if right ventricular longitudinal function assessed using cardiovascular magnetic resonance (CMR) is associated with left ventricular filling pressure in patients with rToF. A second objective of this study was to determine if direction of septal movement is related to right ventricular pressure load in rToF. Eighteen patients with rToF undergoing CMR and heart catheterization prior to pulmonary valve replacement were retrospectively included and catheter-based pressure measurements were compared with CMR-derived RV regional function. Left ventricular filling pressure was measured as precapillary wedge pressure (PCWP). Longitudinal contribution to RV stroke volume correlated with PCWP (r = 0.48; p = 0.046) but not with RV EF or pulmonary regurgitation. Neither RV longitudinal strain nor TAPSE showed correlation with PCWP. Longitudinal contribution to stroke volume was lower for the RV compared to the LV (49 vs 54%; p = 0.039). Direction of septal movement did not show a correlation with RV end-systolic pressure. Right ventricular longitudinal pumping is associated with left ventricular filling pressure in rToF-patients and this inter-ventricular coupling may explain LV underfilling in patients with pulmonary regurgitation and rToF and may be of value to determine right ventricular dysfunction. RV systolic pressure, however, cannot be assessed from the direction of septal movement, in these patients.

Clear cell renal cell carcinoma (ccRCC) is the most common form of renal cancer. Due to inactivation of the von Hippel–Lindau tumour suppressor, the hypoxia‐inducible transcription factors (HIFs) are constitutively activated in these tumours, resulting in a pseudo‐hypoxic phenotype. The HIFs induce the expression of genes involved in angiogenesis and cell survival, but they also reset the cellular metabolism to protect cells from oxygen and nutrient deprivation. ccRCC tumours are highly vascularized and the cytoplasm of the cancer cells is filled with lipid droplets and glycogen, resulting in the histologically distinctive pale (clear) cytoplasm. Intratumoural heterogeneity may occur, and in some tumours, areas with granular, eosinophilic cytoplasm are found. Little is known regarding these traits and how they relate to the coexistent clear cell component, yet eosinophilic ccRCC is associated with higher grade and clinically more aggressive tumours. In this study, we have for the first time performed RNA sequencing comparing histologically verified clear cell and eosinophilic areas from ccRCC tissue, aiming to analyse the characteristics of these cell types. Findings from RNA sequencing were confirmed by immunohistochemical staining of biphasic ccRCC. We found that the eosinophilic phenotype displayed a higher proliferative drive and lower differentiation, and we confirmed a correlation to tumours of higher stage. We further identified mutations of the tumour suppressor p53 (TP53) exclusively in the eosinophilic ccRCC component, where mTORC1 activity was also elevated. Also, eosinophilic areas were less vascularized, yet harboured more abundant infiltrating immune cells. The cytoplasm of clear cell ccRCC cells was filled with lipids but had very low mitochondrial content, while the reverse was found in eosinophilic tissue. We herein suggest possible transcriptional mechanisms behind these phenomena. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

The use of millimeter-wave (mm-wave) frequency bands for fifth-generation (5G) cellular mobile communications has led to intense interest from academia and industry over these spectrum resources. Despite extensive measurement campaigns and channel modeling efforts, there is a lack of deterministic backscattering models addressing the impact of the size and orientation of static scatterers on the radio channel. In this article, two 3-D computationally efficient models for calculating backscattering based on the Fresnel integrals and the error function are proposed and validated both against simulations and measurements. In addition, applying the same methodology, state-of-the-art mm-wave blockage (forward-scattering) models are modified to capture backscattered fields. Furthermore, both the introduced and the modified models preserve the structure of geometry-based stochastic channel models (GSCMs) and thus their implementation in system-level simulators is substantially beneficial due to their good accuracy and short computation time.

Aim: Physical activity is important for health but injuries might affect the level of activity. The aim of this study was to evaluate change in physical activity after fracture and to determine pre...

Introduction: Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years. Methods: The study population included 69 infants with gestational age (GA) 22.3–31.9 weeks (n = 29 with GA Results: Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA Conclusion: Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.

Aim To investigate neurodevelopmental outcome in 12-year-old children born very preterm in relation to perinatal, neonatal and socioeconomic variables. To examine whether previously described positive effects of antenatal steroids on cognition persist at 12 years. Methods Prospective cohort, 78 children with gestational ages 22.7–31.9 weeks, born in 2004–2007 and examined at 12 years of age with cognitive, motor and visual motor integration tasks and compared to an age-matched control group (n = 50). Two preterm subgroups were studied: very preterm children (28–31 gestational weeks, n = 53) and extremely preterm children (22–27 gestational weeks, n = 25). Results The preterm children had significantly lower scores on all cognitive, motor and visual motor integration tasks than the controls. Gestational age and maternal education influenced associations differently in the two preterm subgroups. Also, severe retinopathy of prematurity demonstrated strong associations to outcome. In the extremely preterm group, administration of antenatal steroids was associated with better cognition, basic attention, word generation and motor skills. Conclusion At 12 years of age, very preterm children born in the 2000s still have deficits across several neurodevelopmental domains compared to term-born peers. Administration of antenatal steroids has long-lasting associations to cognition and motor skills in extremely preterm-born children.

Renal cell carcinoma (RCC) is a tumour type with an indolent growth pattern and rather vague symptoms. The present study developed a platform for liquid biopsy of RCC based upon the isolation of circulating tumour cells (CTCs). Founded on the observation that RCC tumour cells are considerably larger than leucocytes, the present study employed a microfluidics-based system for isolation of RCC CTCs from whole blood. Using this system, it was revealed that 66% of spiked-in RCC tumour cells could be retrieved using this approach. Furthermore, it was demonstrated that these cells could be molecularly detected with digital PCR using RCC-specific genes down to one tumour cell, whilst avoiding detection in samples lacking tumour cells. Finally, subtype specific transcripts were identified to distinguish the different subtypes of RCC, which were then validated in patient tumours. The present study established a novel workflow for the isolation of RCC CTCs from whole blood, with the potential to detect these cells irrespective of subtype.

To fulfil the global sustainable development goals (SDGs), achieving sustainable development is becoming urgent, not least in the transportation sector. In response to this, the sustainability framework Sustainability National Road Administrations (SUNRA) was developed to contribute to improving the sustainability performance of national road administrations across Europe. In the present study, the framework has been tested, applied and further developed to be applicable for target setting and follow-up at the project level at both the Swedish Transport Administration (STA) and at municipal levels. The aim was a framework relevant for investment, re-investments, maintenance and operation projects and also to make it more user applicable. The study also investigated how the framework can contribute to sustainability, identified drivers and barriers for applying the framework and examined whether the framework can be applied and adapted to projects of different complexities. The adaptations and developments were done in collaboration between researchers and practitioners. The results show that the framework could easily be used and adapted for investment, re-investment, maintenance and operation projects in the planning stage, as well as for small municipal establishments, construction or reconstruction of residential areas and frequent maintenance. The framework contributes to increased awareness on sustainability, and it provides a common structure and transparency on how infrastructure project goals/targets are set and fulfilled. The framework can also be applied to follow the fulfilment of the goals/targets and thereby adapt the project to better fulfil the goals. Identified barriers include the lack of obligations and lack of experience in using sustainability frameworks. Funding Agencies|MISTRA (Stiftelsen for miljostrategisk forskning), through the research program Mistra Infra Maint Projects [1.12, 1.8]; Swedish Transport Administration [10609]; library of the KTH Royal Institute of Technology

Background: The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated in cancer drug resistance, metastasis, and immunosuppression and has been identified as a promising therapeutic target for new anticancer drugs. Myeloid-derived suppressor cells (MDSCs) play a major role in the suppression of antitumor immunity and STAT3 is involved in the accumulation, generation, and function of MDSCs. Thus, targeting STAT3 holds the potential of reversing immunosuppression in cancer. This study aims to investigate the effect of the small molecule STAT3 inhibitor galiellalactone on prostate cancer cell– induced generation of MDSCs from monocytes and the effect on immunosuppressive factors and inflammatory cytokines. Methods: Primary human monocytes were cocultured with prostate cancer cells (DU145, PC3, and LNCaP-IL6) or with conditioned medium (CM) from prostate cancer cells in the presence or absence of the STAT3 inhibitor galiellalactone. Monocytes were analyzed by flow cytometry for an MDSC-like phenotype (CD14+ HLA-DR−/lo). The secretion and gene expression of immunosuppressive factors and inflammatory cytokines from prostate cancer cells and monocytes were investigated. Results: Galiellalactone blocked the prostate cancer cell–induced generation of MDSC-like monocytes with an immunosuppressive phenotype ex vivo. Monocytes cultured with CM from prostate cancer cells showed increased expression of phosphorylated STAT3. Prostate cancer cells increased the expression of interleukin1β (IL1β), IL10, and IL6 in monocytes which was inhibited by galiellalactone. In addition, galiellalactone decreased indoleamine 2,3-dioxygenase gene expression in monocytes. Galiellalactone reduced the levels of IL8 and granulocyte macrophage-colony stimulating factor in prostate cancer cells per se. Conclusion: The STAT3 inhibitor galiellalactone may prevent the prostate cancer cell–induced generation of MDSCs and reverse the immunosuppressive mechanisms caused by the interplay between prostate cancer cells and MDSCs. This is a potential new immunotherapeutic approach for the treatment of prostate cancer. (Less)

Warsaw breakage syndrome (WABS), caused by bi-allelic variants in the DDX11 gene, is a rare cohesinopathy characterized by pre- and postnatal growth retardation, microcephaly, intellectual disability, facial dysmorphia, and sensorineural hearing loss due to cochlear hypoplasia. The DDX11 gene codes for an iron-sulfur DNA helicase in the Superfamily 2 helicases and plays an important role in genomic stability and maintenance. Fourteen individuals with WABS have been previously reported in the medical literature. Affected individuals have been of various ethnic backgrounds with different pathogenic variants. We report two unrelated individuals of Ashkenazi Jewish descent affected with WABS, who are homozygous for the c.1763-1G>C variant in the DDX11 gene. Their phenotype is consistent with previously reported individuals. RNA studies showed that this variant causes an alternative splice acceptor site leading to a frameshift in the open reading frame. Carrier screening of the c.1763-1G>C variant in the Jewish population revealed a high carrier frequency of 1 in 68 in the Ashkenazi Jewish population. Due to the high carrier frequency and the low number of affected individuals, we hypothesize a high rate of miscarriage of homozygous fetuses and/or subfertility for carrier couples. If the carrier frequency is reproducible in additional Ashkenazi Jewish populations, we suggest including DDX11 to Ashkenazi Jewish carrier screening panels.

Background A recurrent homozygous missense variant, c.160G>C;p.(Val54Leu) in HIKESHI, was found to cause a hypomyelinating leukodystrophy with high frequency in the Ashkenazi Jewish population. We provide extended phenotypic classification of this disorder based on clinical history of a further seven affected individuals, assess carrier frequency in the Ashkenazi Jewish population, and provide a neuropathological study. Methods Clinical information, neuroimaging, and biosamples were collected. Brain autopsy was performed for one case. Results Individuals with HIKESHI-related disease share common clinical features: early axial hypotonia evolving to dystonia or with progressive spasticity, hyperreflexia and clonus, feeding difficulties with poor growth, and nystagmus. Severe morbidity or death during febrile illness occurred in five of the nine affected individuals. Magnetic resonance images of seven patients were analyzed and demonstrated diffuse hypomyelination and thin corpus callosum. Genotyping data of more than 125,000 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 216. Gross pathology examination in one case revealed abnormal white matter. Microscopically, there was a near-total absence of myelin with a relative preservation of axons. The cerebral white matter showed several reactive astrocytes and microglia. Conclusions We provide pathologic evidence for a primary disorder of the myelin in HIKESHI-related leukodystrophy. These findings are consistent with the hypomyelination seen in brain magnetic resonance imaging and with the clinical features of early-onset spastic/dystonic quadriplegia and nystagmus. The high carrier rate of the recurrent variant seen in the Ashkenazi Jewish population requires increased attention to screening and diagnosis of this condition, particularly in this population.

A design concept for a phased-array-fed reflector antenna system intended for millimeter-wave base stations is presented. This concept is motivated by the need for efficient beamforming antenna systems with reduced power consumption as compared to the presently considered fully-populated large-scale MIMO arrays. The main idea is to use a high-gain reflector antenna to maximize the effective isotropic radiated power. That in turn, allows minimizing the number of active antenna elements of the phased-array feed, and hence limit the total supplied power. The proposed reflector antenna system is based on a torus reflector which is illuminated by an offset phased-array feed. We show how to determine the antenna design parameters to achieve the desired cell coverage.

Lower efficiencies of power amplifiers and increased path loss at higher frequencies are two reasons why utilizing millimeter-wave frequencies for future wireless communications systems is challenging. In this paper, two distinct antenna systems are presented which address this challenge by using high antenna gain. This allows lower transmit power levels, compared to conventional phased array antennas, while still providing high effective isotropic radiated power.

This paper presents angular-resolved outdoor-to-indoor measurements on an energy-efficient building with open-plan offices at 28 GHz. The impact of floor level and distance from wall on path loss and angular spread for different indoor traces are presented. Angular spread was shown to have similar behavior on all floors except the floor at the same height as the transmitter. Angular spread does not change for measurement traces parallel to (at constant distance from) the wall but increases with increasing distance from the wall.

Background The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed. Methods Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns. Findings The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR(95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59(1.49-8.62)) associations of the tumour stroma fraction with survival. Interpretation Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance. Funding The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P.O.Zetterling Foundation, and The Sjoberg Foundation, Sweden.

To identify the psychosocial assessments utilized with individuals with conductive and/or mixed hearing loss as part of a broader effort by the Auditory Rehabilitation Outcomes Network (AURONET) group to develop a core set of patient-centred outcome measures. A review of articles published between 2006 and 2016 was completed. Included studies had more than three adult participants, were available in English, and reported a psychosocial outcome from any treatment of mixed and/or conductive hearing loss. Sixty-six articles from seven databases. Sixty-six articles met our inclusion/exclusion criteria. Within this set, 15 unique psychosocial or patient-reported outcome measures (PROs) were identified, with the Abbreviated Profile of Hearing Aid Benefit (APHAB) and Glasgow Benefit Inventory (GBI) being the most frequently dispensed. Five of the fifteen were only administered in one study. In-house questionnaires (IHQs) were reported in 19 articles. Only 66 (22%) of the 300 articles with outcomes contained a PRO. Some of the mostly frequently employed PROs (e.g., APHAB) were judged to include only social items and no psychological items. Lack of PRO standardization and the use of IHQs make psychosocial comparisons across treatments in this population difficult for patients, clinicians and stakeholders.

Partitioning of mobile communication cells using high gain antennas, e.g. lens-horn antennas, has the potential to improve mobile communication links. Depending on the environment, the radiation pattern has to be shaped to achieve optimal coverage. In the case of dual-polarized elliptical-shaped horn antennas, the differences in radiation characteristics for each polarization state has to be considered. In this paper, the design of a compact elliptical lens-horn antenna fed by a circular waveguide is shown. The simulated radiation patterns of the two orthogonal radiation patterns show mainly an influence in the cut along the short axis. In this cut, the beam broadens by 3.8?. Due to the broader beamwidth, the antenna gain reduces by 1.9 dB, which has to be taken into account during the radio planning phase of the cell partitioning.

Background: The availability of an increased proportion of organs from donors after circulatory death (DCD) could solve the organ shortage globally. We present a model of extended uncontrolled DCD (uDCD), allowing sufficient time for the consent procedure in most countries. A novel reconditioning technique allows successful transplantation after prolonged warm ischemia of kidneys from uDCD donors. Methods: Two hours after circulatory death, ice slush was inserted into the abdomen of pigs. Donor organs were then retrieved 4.5 hour after death, and treated on the back-table by injecting Lys-plasminogen, antithrombin-III (AT-III), and alteplase (tPA) through the renal arteries. The kidneys were then perfused with an albumin-rich solution at 15 °C and 20 mmHg for 3 hours. Washed erythrocytes were added to the solution after increasing temperature to 32 °C and pressure to 30 mmHg, continuing the perfusion for another three hours. Argatroban and abciximab were added to inhibit re-thromboses. Reconditioning (study group) kidneys were transplanted into pigs using a novel auto-transplant technique with a single functioning autologous kidney and observed for three months. Sham-treated pigs underwent contra-lateral transplantation of the left kidney after removing the right kidney under the same anesthesia conditions and trauma as study group pigs. Findings: During perfusion, vascular resistance decreased to 100ml/100g/min, significantly higher (p < 0.00018) than kidneys not receiving thrombotlytic treatment. At 3 months post-transplant, 4/6 study and 4/6 control pigs survived. Serum creatinine and renal histology did not differ between the groups. Interpretation: We present a novel method to salvage kidneys from extended uDCD, enabling subsequent transplantation after ex-vivo reconditioning, in a clinically acceptable manner. Funding Information: Supported by grants from IngaBritt and Arne Lundbergs Research Foundation; LUA ALF Grant; The Gelin Foundation and Hans-Gabriel and Alice Trolle Wachtmeister Foundation for Medical Research. Declaration of Interests: MO is the inventor of several patents. None of the other authors reported any potential conflicts of interest Ethics Approval Statement: The Regional (Malmo/Lund) Animal Experiment Ethics Committee approved the study (Dnr 5.8.18‐13977/2018; Dnr 5.8.18‐09474/2019; Dnr 5.8.18‐09182/2020). All animals were housed and cared for in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Resources and published by the National Institute of Health (NIH, Publication No 86‐23, revised 1996).

Aim We investigated the impact of varying definitions on the prevalence of neurodevelopmental impairment (NDI) in children born very preterm at 6.5 years of age. Methods Cognitive development and neurosensory impairments were assessed in 91 children (40/51 girls/boys) born

Aim To study whether a specific cognitive profile can be identified for children born extremely preterm (EPT) by investigating: 1) strengths and weaknesses not revealed by Full-Scale IQ, 2) overlap between different cognitive deficits and 3) proportion of EPT children with multiple deficits. Methods We analysed data from the 4th version of Wechsler Intelligence Scales for Children in EPT children (n = 359) and matched controls (n = 367), collected within the 6.5-year follow-up of a population-based prospective cohort study. Results Extremely preterm children performed worse than controls on all measures. Group differences were the largest in Perceptual Reasoning (PRI) and Working Memory (WMI), but differences between indices were small. However, when conducting categorical analyses, deficits in PRI and/or WMI were not more common than other combinations. Many EPT children had no or mild cognitive deficits, although often in multiple domains. Conclusion Extremely preterm children had greater weaknesses in working memory and perceptual abilities. However, detailed analyses of cognitive subscales showed large heterogeneity and provided no support for a specific cognitive profile. In conclusion, Full-Scale IQ scores hide strengths and weaknesses and individual profiles for EPT children need to be considered in order to provide appropriate support.

Rehabilitation options for conductive and mixed hearing loss are continually expanding, but without standard outcome measures comparison between different treatments is difficult. To meaningfully inform clinicians and patients core outcome sets (COS), determined via a recognised methodology, are needed. Following our previous work that identified hearing, physical, economic and psychosocial as core areas of a future COS, the AURONET group reviewed hearing outcome measures used in existing literature and assigned them into different domains within the hearing core area.Scoping review.Literature including hearing outcome measurements for the treatment of conductive and/or mixed hearing loss.The literature search identified 1434 studies, with 278 subsequently selected for inclusion. A total of 837 hearing outcome measures were reported and grouped into nine domains. The largest domain constituted pure-tone threshold measurements accounting for 65% of the total outcome measures extracted, followed by the domains of speech testing (20%) and questionnaires (9%). Studies of hearing implants more commonly included speech tests or hearing questionnaires compared with studies of middle ear surgery.A wide range of outcome measures are currently used, highlighting the importance of developing a COS to inform individual practice and reporting in trials/research.

The fungal metabolite galiellalactone (1) was, as its acetate 4, discovered to undergo a substitution reaction with cysteine derivatives. By studying the reaction mechanism and the intermediates formed, and in an effort to expand the chemical diversity of the galiellalactonoids, a mild and general method of preparing ether, thioether, and amine analogues of galiellalactone was developed. The reaction is a formal stereoretentive nucleophilic substitution at an oxygenated tertiary carbon. NMR analysis of the progressing reaction shows that it involves an initial allylic substitution to form a new Michael acceptor, followed by the addition of a second equivalent of the nucleophile to this and, finally, a retro Michael reaction. This restores the original galiellalactone system with a double bond between C-2a and C-3, but with a new substituent at C-7b. As galiellalactone is a promising STAT3 inhibitor, this novel transformation facilitates the semisynthesis of a wide variety of new analogues for structure-activity relationship studies.

Background: The development of a reactive tumor stroma is a hallmark of tumor progression. Based on a large number of smaller studies, using different methods, desmoplasia is generally considered associated with poor prognosis. The variability between tumor types regarding stroma fraction, and its prognosis associations, have not been systematically analyzed. Methods: We quantified the tumor stroma in 16 solid cancer types from 2732 patients. The tissue segmentation into stromal and epithelial compartment was performed using objective machine-learning method, driven by a combination of pan-cytokeratin staining, tissue autofluorescence patterns and nuclei characteristics. Findings: Stroma fraction was highly variable within and across the tumor types. Survival analysis in individual tumor types revealed both positive and negative associations of the tumor stroma fraction with survival. A meta-analysis across all cancer types indicated an association of higher stroma fraction with longer survival. Interpretation: Findings strongly argue against the commonly promoted simplistic view of a general associations between high stroma abundance and poor prognosis. Findings also suggest that full exploitation of the prognostic potential of tumor stroma requires analyses that go beyond determination of stroma abundance. Funding Statement: This study was partly supported by The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, Sweden, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P. O. Zetterling Foundation, and The Sjoberg Foundation, Sweden. Image annotation was provided by HistoOne AB, Uppsala, Sweden (https://histo.one). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statements: Colon Cancer (CC) and Rectal Cancer (RC) patient cohort - (Ethical approval Uppsala, 116/07; 419/15). Pariampullary Cancer of intestinal (PACi) and pancreatobiliary (PACpb) type patient cohort - (Ethical approval Lund, 445/07). Ovarian Cancer (OVC) patient cohort - (Ethical approval Lund, 445/07). High Grade Serous Ovarian Cancer (HGSC) patient cohort - (Ethical approval Stockholm, 2016/551–32). Renal Clear Cell (RCC) patient cohort - (Ethical approval Malmo, 282/07). Urine Bladder Cancer (UBC) patient cohort - (Ethical approval Uppsala, 2005/143). Endometrial Cancer (ENC) patient cohort - (Ethical approval Helsinki, 2016/010). Non Small Cell Lung Cancer presented as Lung Squamous Cell Carcinoma (LUSC) and Lung Adenocarcinoma (LUAD) patient cohort - (Ethical approval Uppsala, 532/12). Gastroesophageal Junction Adenocarcinoma (GECA) and Stomach Cancer (SC) patient cohort - (Ethical approval Lund, 445/07). Prostate Cancer (PC) patient cohort - (Ethical approval Lund, 494/05). Breast Cancer (BRC ER- and ER+) patient cohort - (Ethical approval Uppsala, Umea, 2005/118/2).

Background The role of B-lymphocytes in solid tumours is unclear. Tumour biology studies have implied both anti- and pro-tumoural effects and prognostic studies have mainly linked B-cells to increased survival. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking. Methods Following immunohistochemistry (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in an RCC discovery- and validation cohort. Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset. Results IHC analyses of the discovery cohort identified a previously unrecognised subgroup of RCC patients with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed significantly shorter survival according to uni- and multi-variable analyses. The association between poor prognosis and high density of CD20+ B-cells was confirmed in the validation cohort. Analyses of the KIRC gene expression dataset using the B-cell signature confirmed findings from IHC analyses. Analyses of other gene expression datasets, representing 13 different tumour types, indicated that the poor survival-association of B-cells occurred selectively in RCC. Conclusion This exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.

Here, we propose a fully metallic implementation of a Luneburg lens operating at Ka-band with potential use for 5G communications. The lens is implemented with a parallel plate that is loaded with glide-symmetric holes. These holes are employed to produce the required equivalent refractive index profile of a Lune-burg lens. Glide symmetry and inner metallic pins are employed to increase the equivalent refractive index. The lens is fed with rectangular waveguides designed to match the height of the parallel plate, and it is ended with a flare to minimize the reflections.

Objective: To compare the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with those of the linear incision technique with soft-tissue preservation for bone-anchored hearing systems (BAHS). Design: Sponsor-initiated multicenter, open, randomized, controlled clinical trial. Setting: Maastricht University Medical Centre, Ziekenhuisgroep Twente and Medisch Centrum Leeuwarden, all situated in The Netherlands. Participants: Sixty-four adult patients eligible for unilateral BAHS surgery. Interventions Single-stage BAHS surgery with 1:1 randomization to the linear incision technique with soft-tissue preservation (control) or the MIPS (test) group. Primary and Secondary Outcome Measurements: Primary objective: compare the incidence of inflammation (Holgers Index ≥ 2) during 12 weeks’ follow-up after surgery. Secondary objectives: skin dehiscence, pain scores, loss of sensibility around the implant, soft-tissue overgrowth, skin sagging, implant extrusion, cosmetic results, surgical time, wound healing and Implant Stability Quotient measurements. Results: Sixty-three subjects were analyzed in the intention-to-treat population. No significant difference was found for the incidence of inflammation between groups. Loss of skin sensibility, cosmetic outcomes, skin sagging, and surgical time were significantly better in the test group. No statistically significant differences were found for dehiscence, pain, and soft-tissue overgrowth. A nonsignificant difference in extrusion was found for the test group. The Implant Stability Quotient was statistically influenced by the surgical technique, abutment length, and time. Conclusion: No significant differences between the MIPS and the linear incision techniques were observed regarding skin inflammation. MIPS results in a statistically significant reduction in the loss of skin sensibility, less skin sagging, improved cosmetic results, and reduced surgical time. Although nonsignificant, the implant extrusion rate warrants further research.

Background The number of potential options for rehabilitation of patients with conductive or mixed hearing loss is continually expanding. To be able to inform patients and other stakeholders, there is a need to identify and develop patient-centred outcomes for treatment of hearing loss. Objective of review To identify outcome measures in the physical core area used when reporting the outcome after treatment of conductive and mixed hearing loss in adult patients. Type of review Systematic review. Search strategy Systematic review of the literature related to reported physical outcome measures after treatment of mixed or conductive hearing loss without restrictions regarding type of intervention, treatment or device. Evaluation method Any measure reporting the physical outcome after treatment or intervention of mixed or conductive hearing loss was sought and categorised. The physical outcome measures that had been extracted were then grouped into domains. Results The literature search resulted in the identification of 1434 studies, of which 153 were selected for inclusion in the review. The majority (57%) of papers reported results from middle ear surgery, with the remainder reporting results from either bone conduction hearing devices or middle ear implants. Outcomes related to complications were categorised into 17 domains, whereas outcomes related to treatment success was categorised into 22 domains. Conclusions The importance of these domains to patients and other stakeholders needs to be further explored in order to establish which of these domains are most relevant to interventions for conductive or mixed hearing loss. This will allow us to then assess which outcome measures are most suitable for inclusion in the core set.

Objective To study the effect of implanting the percutaneous bone‐anchored hearing system (BAHS) itself and inflammation of the peri‐abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri‐implant skin inflammation. Materials and Methods During surgery and 12 weeks post‐implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL‐1β, IL‐6, IL‐8, TNFα, IL‐17, IL‐10, TGF‐ß, MIP‐1α, MMP‐9, TIMP‐1, COL1α1, VEGF‐A, FGF‐2 TLR‐2, and TLR‐4 was quantified using qRT‐PCR. Results Thirty‐five patients agreed to the surgery and 12‐week biopsy. Twenty‐two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft‐tissue preservation. Five biopsies were obtained during episodes of inflammation. The post‐implantation mRNA expression of IL‐1β (P = .002), IL‐8 (P = .003), MMP9 (P = .005), TIMP‐1 (P = .002), and COL1α1 (P < .001) was significantly up‐regulated. IL‐6 (P = .009) and FGF‐2 (P = .004) mRNA expression was significantly down‐regulated after implantation. Within patients, no difference between post‐implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL‐1β (P = .015) and IL‐17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12‐week follow‐up. Conclusions As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL‐8 and IL‐1β) is still relatively high compared with the baseline, steady‐state, expression. The up‐regulation of anabolic (COL1α1) and tissue‐remodeling (MMP‐9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL‐1β, IL‐17, and TNF‐α may be interesting markers associated with inflammation.