Teemanumeron saatteeksi : ajattelevan maiseman kerrostumia

Itämerensuomalaiset tarkastelivat maisemaa kysymysten sarjana. He lähestyivät maisemaa pienten ja suurten kysymysten muodostamana aineellisena ja aineettomana karttana, joka ylti yksittäisen ihmisen arjen arvoituksista maailman synnyn syövereihin. Claude Lévi-Straussin mukaan myytit ajattelevat meissä (Siikala 2013, 20). Maiseman meille muovaamat arvoitukset eivät ole kadonneet jääkauden jälkeisenä aikana mihinkään. Kun nykyihminen istuu illan tullen rantanuotiolla tai vaaran laella aamun sarastaessa, maisema tiedustelee pelkällä olemassaolollaan: mikä minä olen, mistä olen tullut, mikä minua muovaa ja miten ehkä muutun tulevaisuudessa? Mikä minun paikkani on ihmisen maailmassa?  </p

Hard Instances of the Constrained Discrete Logarithm Problem

The discrete logarithm problem (DLP) generalizes to the constrained DLP, where the secret exponent $x$ belongs to a set known to the attacker. The complexity of generic algorithms for solving the constrained DLP depends on the choice of the set. Motivated by cryptographic applications, we study sets with succinct representation for which the constrained DLP is hard. We draw on earlier results due to Erd\"os et al. and Schnorr, develop geometric tools such as generalized Menelaus' theorem for proving lower bounds on the complexity of the constrained DLP, and construct sets with succinct representation with provable non-trivial lower bounds

Natural course of Fabry disease with the p Arg227Ter (pR227*) mutation in Finland: Fast study

BackgroundFabry disease is caused by a deficient or an absent alfa‐galactosidase A activity and is an X‐linked disorder that results in organ damage and a shortened life span, especially in males. The severity of the disease depends on the type of mutation, gender, skewed X‐chromosome inactivation, and other still unknown factors.MethodsIn this article, we describe the natural course of a common classic Fabry disease mutation, p.Arg227Ter or p.R227*, in Finland.ResultsFour males and ten females belonged to two extended families. The mean age was 46 years (SD 18.4). Six patients (43%) had cardiac hypertrophy, three patients (21%) had ischemic stroke, and none had severe kidney dysfunction. Three patients had atrial fibrillation; two patients who had atrial fibrillation also had pacemakers. All males over 30 years of age had at least one of the following manifestations: cardiac hypertrophy, stroke, or proteinuria. In females, the severity of Fabry disease varied from classic multiorgan disease to a condition that mimicked the attenuated cardiac variant. No one was totally asymptomatic without any signs of Fabry disease. Cardiac magnetic resonance imaging was performed on nine of 14 patients was the most sensitive for detecting early cardiac manifestations. Five patients (55%) had late gadolinium enhancement‐positive segments.ConclusionCardiac involvement should be effectively detected in females before considering them asymptomatic mutation carriers.</div

Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex

Abstract Background and aims Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers. Methods QST data of 1252 patients (669 female, 583 male) with PNI (n=342), PNP (n=571) or CRPS (n=339), and average pain intensity reports from previously published studies were included. Absolute and z-values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects. Results Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (pPeer reviewe

Keinot edistää sää- ja ilmastoriskien hallintaa

ELASTINEN-tutkimushankkeessa selvitettiin sää- ja ilmastoriskien hallinnan tilaa Suomessa ja arvioitiin riskienhallintakeinoja sekä eri toimijoiden roolia. Lisäksi tarkasteltiin, miten riskienhallinnan kustannuksia ja hyötyjä arvioidaan sekä miten riskienhallinta voidaan kääntää liiketoiminnaksi. Yhteiskunnan toimivuuden ja turvallisuuden ylläpitäminen edellyttää aktiivista varautumista sään ääriilmiöihin. Hankkeen tulosten mukaan suomalaiset organisaatiot eivät usein arvioi sää- ja ilmastoriskejä systemaattisesti. Varautumisessa tulee ottaa huomioon, että ilmastonmuutos voi muuttaa sään ääri-ilmiöitä, niiden esiintymistiheyttä ja voimakkuutta. Näin varautuminen sään ääri ilmiöihin on myös osa sopeutumista ilmastonmuutokseen. ELASTINEN-hanke esittää kolme suositusta, joilla sää- ja ilmastoriskien hallintaa voitaisiin parantaa ja sopeutumistyötä tukea: 1) monipuolistetaan tiedon tuottoa ja käyttöä, 2) vahvistetaan yhteistyötä ja kehitetään toimintatapoja sekä 3) kehitetään palveluita ja liiketoimintamahdollisuuksia. Suositusten toteuttamiseksi esitetään toimenpide-ehdotuksia, minkä lisäksi on tunnistettu toimien toteuttajatahoja. Nykyistä monipuolisempi ja helpommin saatavilla oleva tieto parantaisi mahdollisuuksia arvioida ja hallita sää- ja ilmastoriskejä sekä kykyä sopeutua ilmastonmuutoksen vaikutuksiin. Suomessa tulisi myös arvioida säännöllisesti Suomen ulkopuolella tapahtuvia ilmastonmuutoksen vaikutuksia, jotka voivat heijastua Suomeen. Sää- ja ilmastoriskien hallintatoimia tulisi valita ja arvioida myös taloudellisen tehokkuuden näkökulmasta

Translation and cultural adaptation of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale into Arabic for use with patients with diabetes in Libya.

In Libya neuropathic pain is rarely assessed in patients with diabetes. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale is used worldwide to screen for neuropathic pain. There is no Arabic version of LANSS for use in Libya. The aim of this study was to develop an Arabic version of LANSS and to assess its validity and reliability in diabetic patients in Benghazi, Libya. LANSS was translated into Arabic by four bilingual translators and back translated to English by a university academic. Validity and reliability of the Arabic LANSS was assessed on 110 patients attending a Diabetes Centre in Benghazi. Concurrent validity was tested and compared with the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS). Test-retest reliability was conducted 1-2 weeks later. Internal consistency and inter-class correlation (ICC) between LANSS and S-LANSS was also tested. Internal consistency within first completion of the Arabic LANSS was acceptable (Cronbach's alpha = 0.793) and similar to the Arabic S-LANSS (0.796) and the second completion of the Arabic LANSS (0.795). ICC between the Arabic LANSS and the Arabic S-LANSS was 0.999 (p 0.95, p < 0.0001). We concluded that the Arabic version of LANSS pain scale was valid and reliable for use on Libyan diabetic patients. This study provided results suggesting that the S-LANSS could also be used on diabetic patients

Gabapentin for complex regional pain syndrome in Machado-Joseph disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic pain is a common problem for patients with Machado-Joseph disease. Most of the chronic pain in Machado-Joseph disease has been reported to be of musculoskeletal origin, but now there seems to be different chronic pain in patients with Machado-Joseph disease.</p> <p>Case presentation</p> <p>A 29-year-old man (Han Chinese, Hoklo) with Machado-Joseph disease experienced severe chronic pain in both feet, cutaneous thermal change, thermal hypersensitivity, focal edema, and sweating and had a history of bone fracture. These symptoms were compatible with a diagnosis of complex regional pain syndrome. After common analgesics failed to relieve his pain, gabapentin was added and titrated to 2000 mg/day (500 mg every six hours) in less than two weeks. This relieved 40% of his pain and led to significant clinical improvement.</p> <p>Conclusions</p> <p>The pathophysiology of complex regional pain syndrome includes peripheral and central sensitizations, the latter of which might be associated with the neurodegeneration in Machado-Joseph disease. In this report, we suggest that gabapentin could inhibit central sensitization as an adjunct for complex regional pain syndrome in patients with Machado-Joseph disease.</p

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / +, KINSSHIP/KINSSHIP, LoF/ +, LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.</p