| 1. |
- Thompson, B.A., et al.
(author)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Journal article (peer-reviewed)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 2. |
- Ancelle-Park, R., et al.
(author)
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Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet
- 2012
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In: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 19, s. 5-13
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Journal article (peer-reviewed)abstract
- Objectives To construct a European 'balance sheet' of key outcomes of population-based mammographic breast cancer screening, to inform policy-makers, stakeholders and invited women. Methods From the studies reviewed, the primary benefit of screening, breast cancer mortality reduction, was compared with the main harms, over-diagnosis and false-positive screening results (FPRs). Results Pooled estimates of breast cancer mortality reduction among invited women were 25% in incidence-based mortality studies and 31% in case-control studies (38% and 48% among women actually screened). Estimates of over-diagnosis ranged from 1% to 10% of the expected incidence in the absence of screening. The combined estimate of over-diagnosis for screened women, from European studies correctly adjusted for lead time and underlying trend, was 6.5%. For women undergoing 10 biennial screening tests, the estimated cumulative risk of a FPR followed by non-invasive assessment was 17%, and 3% having an invasive assessment. For every 1000 women screened biennially from age 50-51 until age 68-69 and followed up to age 79, an estimated seven to nine lives are saved, four cases are over-diagnosed, 170 women have at least one recall followed by non-invasive assessment with a negative result and 30 women have at least one recall followed by invasive procedures yielding a negative result. Conclusions The chance of saving a woman's life by population-based mammographic screening of appropriate quality is greater than that of over-diagnosis. Service screening in Europe achieves a mortality benefit at least as great as the randomized controlled trials. These outcomes should be communicated to women offered service screening in Europe.
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| 3. |
- Zelenin, Pavel V, et al.
(author)
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Activity of motor cortex neurons during backward locomotion.
- 2011
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In: Journal of Neurophysiology. - 0022-3077.
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Journal article (peer-reviewed)abstract
- Forward walking (FW) and backward walking (BW) are two important forms of locomotion in quadrupeds. Participation of the motor cortex in the control of FW has been intensively studied, while cortical activity during BW has never been investigated. The aim of this study was to analyze locomotion-related activity of the motor cortex during BW, and compare it to that during FW. For this purpose, we recorded activity of individual neurons in the cat during BW and FW. We found that the discharge frequency in almost all neurons was modulated in the rhythm of stepping during both FW and BW. However, the modulation patterns during BW and FW were different in 80% of neurons. To determine the source of modulating influences (forelimb controllers versus hindlimb controllers), the neurons were recorded not only during quadrupedal locomotion, but also during bipedal locomotion (with either forelimbs or hindlimbs walking), and their modulation patterns were compared. We found that during BW (like during FW), modulation in some neurons was determined by inputs from limb controllers of only one girdle, while the other neurons received inputs from both girdles. The combinations of inputs could depend on the direction of locomotion. Most often (in 51% of forelimb-related neurons and in 34% of the hindlimb-related neurons), the neurons received inputs only from their own girdle when this girdle was leading, and from both girdles when this girdle was trailing. This reconfiguration of inputs suggests flexibility of the functional roles of individual cortical neurons during different forms of locomotion.
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| 4. |
- Zelenin, Pavel V, et al.
(author)
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Contribution of Different Limb Controllers to Modulation of Motor Cortex Neurons during Locomotion.
- 2011
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In: The Journal of Neuroscience. - 1529-2401. ; 31:12, s. 49-4636
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Journal article (peer-reviewed)abstract
- During locomotion, neurons in motor cortex exhibit profound step-related frequency modulation. The source of this modulation is unclear. The aim of this study was to reveal the contribution of different limb controllers (locomotor mechanisms of individual limbs) to the periodic modulation of motor cortex neurons during locomotion. Experiments were conducted in chronically instrumented cats. The activity of single neurons was recorded during regular quadrupedal locomotion (control), as well as when only one pair of limbs (fore, hind, right, or left) was walking while another pair was standing. Comparison of the modulation patterns in these neurons (their discharge profile with respect to the step cycle) during control and different bipedal locomotor tasks revealed several groups of neurons that receive distinct combinations of inputs from different limb controllers. In the majority (73%) of neurons from the forelimb area of motor cortex, modulation during control was determined exclusively by forelimb controllers (right, left, or both), while in the minority (27%), hindlimb controllers also contributed. By contrast, only in 30% of neurons from the hindlimb area was modulation determined exclusively by hindlimb controllers (right or both), while in 70% of them, the controllers of forelimbs also contributed. We suggest that such organization of inputs allows the motor cortex to contribute to the right-left limbs' coordination within each of the girdles during locomotion, and that it also allows hindlimb neurons to participate in coordination of the movements of the hindlimbs with those of the forelimbs.
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| 5. |
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| 6. |
- Nyström, Sofia N., et al.
(author)
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AA-Amyloid is cleared by endogenous immunological mechanisms
- 2012
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In: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 19:3, s. 138-145
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Journal article (peer-reviewed)abstract
- Reactive amyloidosis is a complication to longstanding inflammatory diseases.Protein amyloid A (AA), an N-terminal fragment of the acute phase protein serumamyloid A, undergoes conformational changes and is deposited as amyloid in tissue.AA-amyloidosis is reversible and reduction of amyloid mass has been reported as theinflammation ceases. Not much is known about the endogenous factors thatcontribute to amyloid resolution. Herein, we describe the dynamics of amyloiddegradation in experimental murine AA-amyloidosis and show that amyloiddegradation depends on macrophages and antibody formation. AA-amyloidosis wasinduced in mice and resolution of amyloid was monitored over time by histologicaltechniques. Internalized amyloid was present in macrophages that appeared at siteof deposition. At 9 months, when virtually all amyloid was cleared, amyloidosis wasre-induced in one group of animals by a single silver nitrate injection. This causedeposition of excessive amounts of amyloid, and indicate that even thoughundetectable the amyloid reseed in the body and can there act as amyloid enhancingfactor. Antibodies directed against protein AA were detected in animals duringamyloid clearance by ELISA-technique. Passive immunization with an amyloidspecific monoclonal antibody, produced by a B-cell clone recovered from an animalwith advanced AA-amyloidosis, diminish amyloid deposits in murine AA-amyloidosis.Immunoglobulins co-localize with amyloid deposits and can contribute to amyloiddegradation by Fc-receptor mediated phagocytosis.
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| 7. |
- Thyresson, Matilda, et al.
(author)
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Tracing value chains to understand effects of trade on coral reef fish in Zanzibar, Tanzania
- 2013
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In: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 38, s. 246-256
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Journal article (peer-reviewed)abstract
- Coral reef fish are an important source of food security and income for human coastal populations. They also underpin ecosystem processes vital for the future ability of coral reefs to generate ecological goods and services. Identifying socio-economic drivers behind the exploitation of fish that uphold these key ecosystem processes and the scales at which they operate is therefore critical for successful management. This study addresses this issue by examining the reef-associated fish value chain in Zanzibar, and how it links to functional groups of fish and maturity stage of fish within these groups. Semi-structured interviews with 188 respondents (fishers, traders and hotel staff) involved in the fisheries and trade with reef-associated fish in Zanzibar and participatory observations were used. The trade with reef fish in Zanzibar is a complex structure involving many different agents and this study shows that these different agents exhibit differential preferences regarding fish functional groups and/or maturity stages within these groups. Consequently, both high and low trophic species, as well as small and large fishes are fished and sold, which leaves no refuge for the fish assemblage to escape fishing. When other market agents than fishers have so much influence and there are few alternative income generating activities, it is not possible to put all burden on fishers. Management measures that extend down the value chain to include all market agents as well as their links to ecosystem processes are thus likely to be needed to reach the target of sustainable fisheries.
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