Avioero-osituksen sovittelu

Tutkielman aiheena ja tutkimusongelmana on avioero-osituksen sovittelusäännös erityisesti harkintakriteerien osalta ja millaiseksi osituksen sovittelusäännöksen harkintakriteerien sisältö on muotoutunut lain esitöiden, oikeuskirjallisuuden sekä oikeuskäytännön perusteella. Aviovarallisuusyhteyden purkamiseen liittyvä sääntely on edelleen ajankohtaista yhteiskunnassamme ja siten myös ajatus varallisuuden oikeudenmukaisesta jakamisesta. Sovittelusäännös on myös osa varallisuuden oikeudenmukaista jakoa silloin, kun puolittamisperiaatteen puhdas noudattaminen tai omaisuuden erottelu johtaisi kohtuuttomuuteen. Tutkielman tarkoituksena on selventää harkintakriteerien sisältöä osana sovitteluharkintaa. Sovittelusäännös on avoin normi, joten tarkoituksena on nostaa esiin esitöissä, oikeuskirjallisuudessa sekä oikeuskäytännössä syntyneet määritelmät, painotukset ja mahdolliset oikeusohjeet. Tutkielman tarkoituksena on myös nostaa sovittelusäännös tuoreemman tarkastelun kohteeksi, sillä vaarana avoimen normin osalta on, että tämä saattaa jäädä harvoin sovellettavaksi poikkeussäännökseksi, vaikka edellytykset sovitteluun olisivat olemassa. Tutkielmassa olen käyttänyt lainopillista näkökulmaa. Tärkeimpänä kirjallisuuslähteenä on käytetty Pertti Välimäen väitöskirjaa Osituksen sovittelu vuodelta 1995, mutta myös lain esitöillä, muulla oikeuskirjallisuudella sekä oikeuskäytännöllä on ollut tutkielmassani keskeinen merkitys. Tutkielman perusteella osituksen sovittelusäännöksen yleisille edellytyksille tai harkintakriteereille ei löydy yksityiskohtaisia määritelmiä. Lain esitöiden, oikeuskirjallisuuden sekä oikeuskäytännön perusteella on kuitenkin löydettävissä sovitteluharkintaa täsmentäviä kannanottoja eikä kyse ole siten säännöksestä, jolla ei ole yksittäistapauksen ulkopuolella merkityssisältöä. Selkeää on, että panostukseen viittaavat harkintakriteerit saavat suuremman painoarvon sovitteluharkinnassa, mutta esimerkiksi tarveperusteitakaan ei ole täysin torjuttu. Osituksen sovittelusäännös olisi kuitenkin hyvä ottaa laajemman tutkimuksen kohteeksi, jotta saadaan selville, miten osituksen sovittelusäännös harkintakriteereineen nähdään oikeusoppineiden keskuudessa käytännössä, mutta tutkimus olisi tarpeellista myös siksi, että voidaan arvioida, pystyykö osituksen sovittelusäännös edelleen sellaisenaan vastaamaan nyky-yhteiskunnan uusiin instituutioihin

BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients

Although new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) +/- MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75-89) were treated with BRAFi +/- MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, response rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1-2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0-57), and the median OS was 15 months (range 0-71). Tailored BRAFi +/- MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting responses. Hence, it seems that older patients may benefit from BRAFi treatment.Peer reviewe

Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Objective: Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients. Design: A retrospective single-institution study. Methods: We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed the endocrine toxicity and the best possible treatment outcomes from electronic patient records, including laboratory parameters and radiological images. Results: Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and 6 (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1-11.1 months vs 2.7 months, range 2.4-3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5-79.5 months vs 23.7 months, range 15.3-32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs. Conclusions: The higher number of endocrine AEs suggest that regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.Peer reviewe

A real-time health notification system aimed at enhancing the interaction between animal care staff and researchers promotes animal welfare

Regardless of the microbiological status of an animal facility, research animals may experience health problems, leading to pain, suffering and distress. Simple and efficient tools are needed to collect data systematically, allowing researchers to react and resolve animals' health issues. We have developed a real-time notification method for recording clinical observations, which caretakers can input into the ELLI record-keeping system, accompanied by a picture or video. A browser-based interface system sends alerts using a three-tier scale (+, 120 hours; ++, 72 hours; +++, 24 hours) by email and/or SMS. The percentage of animal health notifications for rodents was 1.31% in 2016, 1.33% in 2017 and 1.58% in 2018, with 34-44% for coat and skin conditions (wounds, bites and scratches). All other notifications, including environment and behaviour, procedure-specific indicators (weight loss, bleeding and abnormal secretions) and other abnormalities such as eye and teeth malformations, ranged from 5% to 10% during the three-year period. Researchers displayed good compliance by reacting to the notifications within the expected time frame. Most health notifications concerned genetically modified (GM) animals without a predetermined harmful phenotype, regardless of being on project licence or maintenance licence. Health notification records may be useful retrospectively not only to review the health and welfare issues of new GM lines but also to evaluate the actual severity of procedures. The health notification system described here provides valuable information to the veterinarian and the animal welfare body by helping to address specific health conditions and to improve animal welfare and implement the 3Rs

In vivo Induction of Functional Inhibitory IgG Antibodies by a Hypoallergenic Bet v 1 Variant

Allergic sensitization to the major allergen Bet v 1 represents the dominating factor inducing a vast variety of allergic symptoms in birch pollen allergic patients worldwide, including the pollen food allergy syndrome. In order to overcome the huge socio-economic burden associated with allergic diseases, allergen-specific immunotherapy (AIT) as a curative strategy to manage the disease was introduced. Still, many hurdles related to this treatment exist making AIT not the patients' first choice. To improve the current situation, the development of hypoallergen-based drug products has raised attention in the last decade. Herein, we investigated the efficacy of the novel AIT candidate BM4, a hypoallergenic variant of Bet v 1, to induce treatment-relevant cross-reactive Bet v 1-specific IgG antibodies in two different mammals, Wistar rats and New Zealand White rabbits. We further analyzed the cross-reactivity of BM4-induced Wistar rat antibodies with the birch pollen-associated food allergens Mal d 1 and Cor a 1, and the functional capability of the induced antibodies to act as IgE-blocking IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) was used to determine the titers of rat IgG1, IgG2a, IgG2b, and IgE, as well as rabbit IgG and IgE antibodies. To address the functional relevance of the induced IgG antibodies, the capacity of rat sera to suppress binding of human IgE to Bet v 1 was investigated by using an inhibition ELISA and an IgE-facilitated allergen-binding inhibition assay. We found that the treatment with BM4 induced elevated Bet v 1-specific IgG antibody titers in both mammalian species. In Wistar rats, high BM4-specific IgG1, IgG2a, and IgG2b titers (10(4)to 10(6)) were induced, which cross-reacted with wild-type Bet v 1, and the homologous allergens Mal d 1 and Cor a 1. Rat allergen-specific IgG antibodies sustained upon treatment discontinuation. Sera of rats immunized with BM4 were able to significantly suppress binding of human IgE to the wild-type allergens and CD23-mediated human IgE-facilitated Bet v 1 binding on B cells. By contrast, treatment-induced IgE antibody levels were low or undetectable. In summary, BM4 induced a robust IgG immune response that efficiently blocked human IgE-binding to wild-type allergens, underscoring its potential therapeutic value in AIT

A method to collect high volumes of milk from mice (Mus musculus)

Collecting milk samples from mice (Mus musculus) may be interesting for a variety of preclinical research. References in the literature for protocols describing how to milk a dam are scarce, and a major limitation of such protocols is the small sample volume that is generally collected. The aim of our study was to develop a practical protocol to collect substantial amounts of milk from mice. Adult female outbred NMRI and inbred BALB/c mice with nursing litters were used in this study. The milking was carried out on days 7–12 after parturition. The pups were separated from their mothers for 6–12 h before milking to allow accumulation of milk in the glands. Dams were anesthetized using either an injectable mixture of midazolam and ketamine, or by use of the inhalational agent isoflurane. To induce milk flow, the mice were given 2-8 IU of oxytocin intraperitoneally. The milk was collected using an electric human breast pump that was modified to accommodate mouse nipples and to handle small liquid volumes. With this protocol, the total amount of milk collected from each dam per each milking ranged between 0.2 and 1.5 mL. We concluded that this milking method provides an excellent means for acquiring substantial amounts of mouse milk.La obtención de leche a partir de ratones de laboratorio (Mus musculus) podría ser interesante para una gran variedad de estudios preclínicos. Son muy escasas las referencias en la literatura científica sobre protocolos que describan como obtener estas muestras, siendo la principal limitación de tales protocolos el pequeño volumen de muestra que es habitual obtener. El objetivo de nuestro estudio fue desarrollar un método funcional para obtener fácilmente cantidades considerables de leche de ratón. Hembras adultas de la variedad no consanguíneas NMRI y de la consanguínea BALB/c con su camada fueron utilizadas en este estudio. La leche fue recogida entre los días 7-12 tras el parto. Las crías fueron separadas de sus madres entre 6-12 horas antes del ordeño para permitir la acumulación de leche en las glándulas. Las hembras fueron anestesiadas usando o una mezcla de midazolam y ketamina, o empleando isoflurano como agente inhalatorio. Para inducir la eyección de la leche, se administro una dosis de 2-8 UI de oxitocina intraperitonealmente. La leche fue recogida usando un sacaleches eléctrico para humanos que fue modificado para adaptarse al pezón de los ratones y para recoger pequeños volúmenes. Con este procedimiento, la cantidad de leche obtenida de los ratones osciló entre los 0,2 y los 1,5 ml. Concluimos por tanto, que este método proporciona una excelente manera de adquirir cantidades considerables de leche de ratón

In vivo Induction of Functional Inhibitory IgG Antibodies by a Hypoallergenic Bet v 1 Variant

Allergic sensitization to the major allergen Bet v 1 represents the dominating factor inducing a vast variety of allergic symptoms in birch pollen allergic patients worldwide, including the pollen food allergy syndrome. In order to overcome the huge socio-economic burden associated with allergic diseases, allergen-specific immunotherapy (AIT) as a curative strategy to manage the disease was introduced. Still, many hurdles related to this treatment exist making AIT not the patients’ first choice. To improve the current situation, the development of hypoallergen-based drug products has raised attention in the last decade. Herein, we investigated the efficacy of the novel AIT candidate BM4, a hypoallergenic variant of Bet v 1, to induce treatment-relevant cross-reactive Bet v 1-specific IgG antibodies in two different mammals, Wistar rats and New Zealand White rabbits. We further analyzed the cross-reactivity of BM4-induced Wistar rat antibodies with the birch pollen-associated food allergens Mal d 1 and Cor a 1, and the functional capability of the induced antibodies to act as IgE-blocking IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) was used to determine the titers of rat IgG1, IgG2a, IgG2b, and IgE, as well as rabbit IgG and IgE antibodies. To address the functional relevance of the induced IgG antibodies, the capacity of rat sera to suppress binding of human IgE to Bet v 1 was investigated by using an inhibition ELISA and an IgE-facilitated allergen-binding inhibition assay. We found that the treatment with BM4 induced elevated Bet v 1-specific IgG antibody titers in both mammalian species. In Wistar rats, high BM4-specific IgG1, IgG2a, and IgG2b titers (104 to 106) were induced, which cross-reacted with wild-type Bet v 1, and the homologous allergens Mal d 1 and Cor a 1. Rat allergen-specific IgG antibodies sustained upon treatment discontinuation. Sera of rats immunized with BM4 were able to significantly suppress binding of human IgE to the wild-type allergens and CD23-mediated human IgE-facilitated Bet v 1 binding on B cells. By contrast, treatment-induced IgE antibody levels were low or undetectable. In summary, BM4 induced a robust IgG immune response that efficiently blocked human IgE-binding to wild-type allergens, underscoring its potential therapeutic value in AIT

A method to collect to high volumes of milk from mice (Mus musculus)

ABSTRACT Collecting milk samples from mice (Mus musculus) may be interesting for a variety of preclinical research. References in the literature for protocols describing how to milk a dam are scarce, and a major limitation of such protocols is the small sample volume that is generally collected. The aim of our study was to develop a practical protocol to collect substantial amounts of milk from mice. Adult female outbred NMRI and inbred BALB/c mice with nursing litters were used in this study. The milking was carried out on days 7–12 after parturition. The pups were separated from their mothers for 6–12 h before milking to allow accumulation of milk in the glands. Dams were anesthetized using either an injectable mixture of midazolam and ketamine, or by use of the inhalational agent isoflurane. To induce milk flow, the mice were given 2-8 IU of oxytocin intraperitoneally. The milk was collected using an electric human breast pump that was modified to accommodate mouse nipples and to handle small liquid volumes. With this protocol, the total amount of milk collected from each dam per each milking ranged between 0.2 and 1.5 mL. We concluded that this milking method provides an excellent means for acquiring substantial amounts of mouse milk.RESUMEN La obtención de leche a partir de ratones de laboratorio (Mus musculus) podría ser interesante para una gran variedad de estudios preclínicos. Son muy escasas las referencias en la literatura científica sobre protocolos que describan como obtener estas muestras, siendo la principal limitación de tales protocolos el pequeño volumen de muestra que es habitual obtener. El objetivo de nuestro estudio fue desarrollar un método funcional para obtener fácilmente cantidades considerables de leche de ratón. Hembras adultas de la variedad no consanguíneas NMRI y de la consanguínea BALB/c con su camada fueron utilizadas en este estudio. La leche fue recogida entre los días 7-12 tras el parto. Las crías fueron separadas de sus madres entre 6-12 horas antes del ordeño para permitir la acumulación de leche en las glándulas. Las hembras fueron anestesiadas usando o una mezcla de midazolam y ketamina, o empleando isoflurano como agente inhalatorio. Para inducir la eyección de la leche, se administro una dosis de 2-8 UI de oxitocina intraperitonealmente. La leche fue recogida usando un sacaleches eléctrico para humanos que fue modificado para adaptarse al pezón de los ratones y para recoger pequeños volúmenes. Con este procedimiento, la cantidad de leche obtenida de los ratones osciló entre los 0,2 y los 1,5 ml. Concluimos por tanto, que este método proporciona una excelente manera de adquirir cantidades considerables de leche de rató