Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1)

Congenital nephrotic syndrome of the Finnish type (NPHS1) is a rare genetic disease caused by mutations in the NPHS1 gene encoding a major podocyte slit-diaphragm protein, nephrin. Patients with NPHS1 have severe nephrotic syndrome from birth and develop renal fibrosis in early childhood. In this work, we studied the development of glomerular sclerosis in kidneys removed from 4- to 44-month-old NPHS1 patients. The pathological lesions and expression of glomerular cell markers were studied in nephrectomized NPHS1 and control kidneys using light and electron microscopy and immunohistochemistry. An analysis of 1528 glomeruli from 20 patients revealed progressive mesangial sclerosis and capillary obliteration. Although few inflammatory cells were detected in the mesangial area, paraglomerular inflammation and fibrosis was common. The podocytes showed severe ultrastructural changes and hypertrophy with the upregulation of cyclins A and D1. Podocyte proliferation, however, was rare. Apoptosis was hardly detected and the expression of antiapoptotic B-cell lymphoma-2 and proapoptotic p53 were comparable to controls. Moderate amounts of podocytes were secreted into the urine of NPHS1 patients. Shrinkage of the glomerular tuft was common, whereas occlusion of tubular opening or protrusion of the glomerular tuft into subepithelial space or through the Bowman's capsule were not detected. The results indicate that, in NPHS1 kidneys, the damaged podocytes induce progressive mesangial expansion and capillary obliteration. Podocyte depletion, glomerular tuft adhesion, and misdirected filtration, however, seem to play a minor role in the nephron destruction

Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation

Background. Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. Methods. In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Delta) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). Results. Positive transrenal gradients of tPA antigen occurred at 1 minute [Delta = 14 (3-46) ng/mL, P <.01] and 5 minutes [Delta = 5 (-3 to 27) ng/mL, P <.01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Delta = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P <.001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P = .006). Conclusions. The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation.Peer reviewe

Partners of nulliparous women with severe fear of childbirth: a longitudinal 1 study of psychological well being

Background: Little is known about the psychological status of partners of women with severe fear of childbirth (FOC). In this longitudinal study from Helsinki University Central Hospital, we investigated FOC, depression and post- traumatic stress in the partners of women with severe FOC, and possible effects of group psychoeducation and mode of birth. Methods: During pregnancy, 250 partners of nulliparous women with severe FOC participated, 93 in the intervention group and 157 in the control group. At three months postpartum 52 partners in the intervention group and 93 in the control group participated. Both the partners and the childbearing women filled in the Wijma Delivery Expectancy Questionnaire and the Edinburgh Postnatal Depression Scale mid-pregnancy as well as three months postpartum, when they also filled in the Traumatic Event Scale. Results: Partners of women with severe FOC reported less antenatal and postnatal FOC and fewer depressive symptoms than the childbearing women. No partner reached the threshold of severe FOC. No partner reported a possible post-traumatic stress disorder. Group psychoeducation with relaxation was not associated with better or worse psychological well being of the partners. An emergency cesarean section 1 was associated with a more fearful delivery experience in the partners. Conclusion: Partners of nulliparous women with severe FOC neither seem to suffer from severe FOC nor reported post-traumatic stress symptoms after childbirth. They reported better psychological well being than the mothers both during pregnancy and after delivery. An unexpected cesarean may be a negative experience even for 6 partners of childbearing women

Exome sequencing reveals independent SGCD deletions causing limb girdle muscular dystrophy in Boston terriers

Background: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked muscle weakness and atrophy in the shoulder and hips during puppyhood. Methods: Following clinical evaluation, the identification of the dystrophic histological phenotype on muscle histology, and demonstration of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome sequencing was performed on five Boston terriers: one affected dog and its three family members and one unrelated affected dog. Results: Within sarcoglycan-delta (SGCD), a two base pair deletion segregating with LGMD in the family was discovered, and a deletion encompassing exons 7 and 8 was found in the unrelated dog. Both mutations are predicted to cause an absence of SGCD protein, confirmed by immunohistochemistry. The mutations are private to each family. Conclusions: Here, we describe the first cases of canine LGMD characterized at the molecular level with the classification of LGMD2F.Peer reviewe

Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions

Healthy people in healthy premises: the Finnish Indoor Air and Health Programme 2018-2028

Clean and fresh indoor air supports health and well-being. However, indoor air can contain pollutants that can cause a variety of symptoms and reduce well-being. Individual exposure agents can also increase the risk of certain diseases. Finns have taken major steps to improve the quality of indoor air for several decades. The primary focus of these activities has been the prevention and reduction of exposure to poor indoor air quality through guidance and regulation directing remediation of damaged buildings. Nevertheless, reported symptoms related to poor indoor air quality are common in Finland. In addition to exposure to indoor air pollutants, this may be partly due to the lively public discussion on the health risks caused by poor indoor air quality, conflicting views between experts, and mistrust towards public authorities, building owners and builders. Because of the scale of the indoor air problems in Finland, people's needs for reliable information and support, and the major costs involved, there is a call for new evidence-based methods, perspectives and solutions. Therefore, the Finnish Institute for Health and Welfare initiated the Finnish Indoor Air and Health Programme 2018-2028 together with a number of collaborators and stakeholders. The primary, long-term objective of the programme is to reduce hazards to health and well-being linked to indoor environments in Finland. To fulfill this objective, the programme will focus on the promotion of human health and well-being, the prevention of hazards, improved communication and engage the whole health-care sector to manage better patients ' symptoms and complaints. The 10-year Finnish Indoor Air and Health Programme consists of four areas that aim (1) to increase understanding of the effects of indoor environments on health and well-being; (2) to develop the management of problems linked to indoor environments; (3) to improve the treatment and working and functional capacity of people with symptoms and illnesses; and (4) to strengthen the competence in matters related to indoor environments. The progress of the programme and reaching the predefined, quantitative goals will be monitored throughout the programme

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Peer reviewe

A Flexible LDPC/Turbo Decoder Architecture

Low-density parity-check (LDPC) codes and convolutional Turbo codes are two of the most powerful error correcting codes that are widely used in modern communication systems. In a multi-mode baseband receiver, both LDPC and Turbo decoders may be required. However, the different decoding approaches for LDPC and Turbo codes usually lead to different hardware architectures. In this paper we propose a unified message passing algorithm for LDPC and Turbo codes and introduce a flexible soft-input soft-output (SISO) module to handle LDPC/Turbo decoding. We employ the trellis-based maximum a posteriori (MAP) algorithm as a bridge between LDPC and Turbo codes decoding. We view the LDPC code as a concatenation of n super-codes where each super-code has a simpler trellis structure so that the MAP algorithm can be easily applied to it. We propose a flexible functional unit (FFU) for MAP processing of LDPC and Turbo codes with a low hardware overhead (about 15% area and timing overhead). Based on the FFU, we propose an area-efficient flexible SISO decoder architecture to support LDPC/Turbo codes decoding. Multiple such SISO modules can be embedded into a parallel decoder for higher decoding throughput. As a case study, a flexible LDPC/Turbo decoder has been synthesized on a TSMC 90 nm CMOS technology with a core area of 3.2 mm2. The decoder can support IEEE 802.16e LDPC codes, IEEE 802.11n LDPC codes, and 3GPP LTE Turbo codes. Running at 500 MHz clock frequency, the decoder can sustain up to 600 Mbps LDPC decoding or 450 Mbps Turbo decoding.NokiaNokia Siemens Networks (NSN)XilinxTexas InstrumentsNational Science Foundatio

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Dissolving the digital divide : Creating coherence in young people's social ecologies of learning and identity building

This chapter discusses current research on educational efforts to connect school learning with young people’s digital practices in- and out-of-school. Instead of focusing on divides between in-school and out-of-school learning or between the “digital generation” and other age groups, in this chapter we discuss what recent research says about the ways in which school can become a space in which young people’s digital practices can transformatively converge with schooling, and how this convergence is related to their learning and identity building. We begin our narrative reflection of current research by focusing on the myth of digital natives. Next, we will conceptualize recent efforts to researching and understanding young people’s engagement, learning and identity building across sites and contexts. We will then turn to illuminating some key rationales of current educational research on creating convergence in young people’s social ecologies via the use of digital technologies and media. We conclude our reflections by pointing out that although there are some promising findings on how digital technologies and media can create convergence in young people’s engagement and learning across sites and contexts, less research attention is given to young people’s personal sense-making and self-making mediated by their digital practices, and how formal education could build on those practices for academic, vocational and/or civic ends.Peer reviewe