A review of early numeracy interventions for children at risk in mathematics

Peer reviewe

Kieli objektina - miten lapset mieltävät kielen?

In this article, children’s views to language are discussed. The data comes from a project called Situated metalinguistic awareness and foreign language learning. It is argued that in children’s conceptualizations, the knowledge and skills that are required at school are separate from the skills of everyday life. For example, the English they learn in everyday life - “Play Station English” - is not identified with the “Classroom English”. It is suggested that the gap between school and everyday life, or, between different school subjects dealing with language (mother tongue and foreign languages) should be better bridged.peerReviewe

Accuracy of preoperative MRI to assess lateral neck metastases in papillary thyroid carcinoma

Primary treatment of papillary thyroid carcinoma (PTC) with lateral lymph node metastasis is surgery, but the extent of lateral neck dissection remains undefined. Preoperative imaging is used to guide the extent of surgery, although its sensitivity and specificity for defining the number and level of affected lymph nodes on the lateral neck is relatively modest. Our aim was to assess the role of preoperative magnetic resonance imaging (MRI) in predicting the requisite levels of neck dissection in patients with regionally metastatic PTC, with a focus on Levels II and V. All patients with PTC and lateral neck metastasis who had undergone neck dissection at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland from 2013 to 2016 and had a preoperative MRI available were retrospectively reviewed. A head and neck radiologist re-evaluated all MRIs, and the imaging findings were compared with histopathology after neck dissection. In the cohort of 39 patients, preoperative MRI showed concordance with histopathology for Levels II and V as follows: sensitivity of 94 and 67%, specificity of 20 and 91%, positive predictive value of 56 and 75%, and negative predictive value of 75 and 87%, respectively. In PTC, MRI demonstrated fairly high specificity and negative predictive value for Level V metastasis, and future studies are needed to verify our results to omit prophylactic dissection of this level. Routine dissection of Level II in patients with regionally metastatic PTC needs to be considered, as MRI showed low specificity.Peer reviewe

Changes in emotions and personal goals in primiparous pregnant women during group intervention for fear of childbirth

The changes in emotions, subjective fear of childbirth, and personal goals were examined during a group intervention to treat fear of childbirth (FOC). The objective was to gain a more detailed understanding of the changes occurring during the group intervention of FOC. The changes in emotions, subjective FOC, and personal goals were studied in primiparous pregnant women with severe FOC participating in a group intervention (n = 105). The group intervention contained six sessions during pregnancy and one after childbirth. At every session, the participants filled in a questionnaire regarding their experiences of current positive and negative emotions and the subjective FOC. The participants also set and reported their personal goals in their preparation for childbirth and parenthood. The negative emotions decreased from the beginning of the intervention. The change became significant after the fourth session. The amount of positive emotions increased but became statistically significant only after the delivery. The subjective FOC decreased significantly from the beginning of the intervention. Personal goals shifted from being mainly self-related to being mostly related to parenthood. The group intervention decreased FOC and promoted changes in emotions and personal goals that foster emotional preparedness for childbirth. It seems that the decrease in FOC was made possible through gaining a better capacity to regulate emotions, especially negative emotions. As negative emotions and fear decreased, personal goals simultaneously changed in the direction known to be adaptive for the new life situation as a parent of a newborn.Peer reviewe

Prognostic Value of Apparent Diffusion Coefficient in Oropharyngeal Carcinoma

Purpose To investigate clinical and radiological factors predicting worse outcome after (chemo)radiotherapy ([C]RT) in oropharyngeal squamous cell carcinoma (OPSCC) with a focus on apparent diffusion coefficient (ADC). Methods This retrospective study included 67 OPSCC patients, treated with (C)RT with curative intent and diagnosed during 2013-2017. Human papilloma virus (HPV) association was detected with p16 immunohistochemistry. Of all 67 tumors, 55 were p16 positive, 9 were p16 negative, and in 3 the p16 status was unknown. Median follow-up time was 38 months. We analyzed pretreatment magnetic resonance imaging (MRI) for factors predicting disease-free survival (DFS) and locoregional recurrence (LRR), including primary tumor volume and the largest metastasis. Crude and p16-adjusted hazard ratios were analyzed using Cox proportional hazards model. Interobserver agreement was evaluated. Results Disease recurred in 13 (19.4%) patients. High ADC predicted poor DFS, but not when the analysis was adjusted for p16. A break in RT (hazard ratio, HR = 3.972, 95% confidence interval, CI 1.445-10.917, p = 0.007) and larger metastasis volume (HR = 1.041, 95% CI 1.007-1.077, p = 0.019) were associated with worse DFS. A primary tumor larger than 7 cm(3) was associated with increased LRR rate (HR = 4.861, 1.042-22.667, p = 0.044). Among p16-positive tumors, mean ADC was lower in grade 3 tumors compared to lower grade tumors (0.736 vs. 0.883; p = 0.003). Conclusion Low tumor ADC seems to be related to p16 positivity and therefore should not be used independently to evaluate disease prognosis or to choose patients for treatment deintensification.Peer reviewe

Lung function and exercise capacity 6 months after hospital discharge for critical COVID-19

Background The significant morbidity caused by COVID-19 necessitates further understanding of long-term recovery. Our aim was to evaluate long-term lung function, exercise capacity, and radiological findings in patients after critical COVID-19. Methods Patients who received treatment in ICU for COVID-19 between March 2020 and January 2021 underwent pulmonary function tests, a 6MWD and CXR 6 months after hospital discharge. Results A restrictive ventilatory defect was found in 35% (23/65) and an impaired diffusing capacity in 52% (32/62) at 6 months. The 6-minute walk distance was reduced in 33% (18/55), and 7% (4/55) of the patients had reduced exercise capacity. Chest X-ray was abnormal in 78% (52/67) at 6 months after hospital discharge. Conclusion A significant number of patients had persisting lung function impairment and radiological abnormalities at 6 months after critical COVID-19. Reduced exercise capacity was rare.Peer reviewe

Kohti hiilineutraalia kuntaa: ilmastoverkoston vaikutus kunnan ilmastotyöhön ja päästöihin

Kunnilla on suuri rooli ilmastonmuutoksen hillitsemisessä. Yhä useampi kunta on asettanut itselleen merkittäviä päästövähennystavoitteita. Tavoitteilla ja suunnitelmilla nähdään olevan tärkeä rooli kansallisen ilmastopolitiikan toteuttamisessa. Kuntien strategioiden yhteyttä päästövähennyksiin on ollut kuitenkin vaikea osoittaa. Edes lisääntyneen ilmastotyön yhteyttä päästövähennyksiin ei ole pystytty suoraan todentamaan. Tässä työssä selvitettiin Kohti hiilineutraalia kuntaa (Hinku) -verkoston vaikutusta kuntien kasvihuonekaasupäästöihin, aurinkosähkön käyttöönottoon ja kuntien ilmastotyöhön. Verkostoon liittyneet kunnat pyrkivät saavuttamaan 80 prosentin kasvihuonekaasupäästövähennyksen vuoteen 2030 mennessä verrattuna vuoden 2007 päästöihin. Työssä tarkasteltiin Manner-Suomen kuntien päästökehitystä tilastollisella analyysillä, jossa useita muun muassa kuntien rakenteeseen, energiajärjestelmään ja maantieteeseen liittyviä tekijöitä kontrolloitiin niin, että Hinku-verkoston vaikutukseen päästiin käsiksi. Tämän lisäksi haastateltiin 40 ennen vuotta 2019 verkostoon liittyneen Hinku-kunnan edustajat. Haastatteluissa kysyttiin Hinku-verkoston roolista kunnan ilmastotyössä. Lisäksi kysyttiin kuntien kohtaamista ilmastotyön haasteista ja onnistumisista, sekä eri toimijoiden rooleista kunnan ilmastotyössä. Työn tulokset osoittavat, että Hinku-verkoston jäsenyydellä ja kunnan kasvihuonekaasupäästöjen välillä on tilastollisesti merkitsevä yhteys. Analyysin mukaan Hinku-verkostoon liittyminen pienentää kunnan päästöjä, niiden ollessa noin 3,1 prosenttia alemmalla tasolla kuin mitä ne olisivat ilman Hinku-verkostoa, kun muut päästöihin vaikuttavat tekijät on huomioitu. Hinkuun liitytään kunnanvaltuuston päätöksellä, usein aktiivisen kunnan avainhenkilön tai verkostoa koordinoivan Suomen ympäristökeskuksen edustajan kannustuksesta. Haastattelujen mukaan johdon sitoutuminen on ollut tärkeää. Usein verkostoon liittyminen on ollut luonnollinen jatkumo kunnassa jo tehdylle ilmastotyölle, mutta liittyminen on voitu nähdä myös uutena avauksena tai imagoa nostattavana tekijänä. Haastattelujen mukaan verkostolta on saatu motivaatiota, inspiraatiota ja vertaistukea. Lähes puolessa haastatelluista kunnista verkoston kautta saatu asiantuntijatuki koettiin arvokkaaksi. Verkostolta oltiin saatu myös viestintätukea ja medianäkyvyyttä. Muutamassa kunnassa Hinkun myötä kunnan strategioihin oltiin lisätty ilmastotyön kirjauksia, joskin monissa kunnissa konkreettiset toimenpiteet olivat lähteneet liikkeelle hitaasti. Ilmastotyön haasteina oli koettu muun muassa organisaatiomuutosten ja henkilövaihdosten vaikutukset Hinku-työn eteenpäin viemiseen, sekä niukat taloudelliset resurssit. Konkreettisia ilmastotoimia oli toisaalta edistänyt se, että niitä oli voitu perustella päättäjille Hinku-jäsenyydellä. Kuntien edustajista 60 prosenttia koki, että Hinku-verkostoon liittyminen on edistänyt päästövähennyksiä konkreettisten toimenpiteiden kautta. Haastattelujen mukaan tärkeimpien konkreettisten toimien joukossa on ollut muun muassa energiantuotantoon, rakennusten energiatehokkuuteen, liikenteeseen ja aurinkosähköön liittyviä toimia. Hinku-kunnat eroavat keskenään suuresti ilmastotyön suunnitelmallisuudessa ja toimeenpanossa. Tässä työssä tunnistetut, ilmastotyössä onnistuneiden kuntien käyttöön ottamat toimenpiteet liittyvät käytännössä kunnan johdon sitoutumiseen, henkilöstön aktiivisuuteen ja työn riittävään resurssointiin. Onnistumisia on koettu, kun ilmastotyö on jalkautettu läpi toimialojen, kokemuksia on vaihdettu, ja ilmastotyöhön on osallistettu useita eri toimijoita. Työn tulosten perusteella Hinku-verkoston keskitetylle tuelle ja kuntien yhteistoiminnalle voidaan suunnitella uusia toimintamalleja

Adenovirus Encoding Tumor Necrosis Factor Alpha and Interleukin 2 Induces a Tertiary Lymphoid Structure Signature in Immune Checkpoint Inhibitor Refractory Head and Neck Cancer

Immune checkpoint inhibitors (ICI) have provided significant improvement in clinical outcomes for some patients with solid tumors. However, for patients with head and neck cancer, the response rate to ICI monotherapy remains low, leading to the exploration of combinatorial treatment strategies. In this preclinical study, we use an oncolytic adenovirus (Ad5/3) encoding hTNF alpha and hIL-2 and non-replicate adenoviruses (Ad5) encoding mTNF alpha and mIL-2 with ICI to achieve superior tumor growth control and improved survival outcomes. The in vitro effect of Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 was characterized through analyses of virus replication, transgene expression and lytic activity using head and neck cancer patient derived cell lines. Mouse models of ICI naive and refractory oral cavity squamous cell carcinoma were established to evaluate the local and systemic anti-tumor immune response upon ICI treatment with or without the non-replicative adenovirus encoding mTNF alpha and mIL-2. We delineated the mechanism of action by measuring the metabolic activity and effector function of CD3(+) tumor infiltrating lymphocytes (TIL) and transcriptomic profile of the CD45(+) tumor immune compartment. Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 demonstrated robust replicative capability in vitro across all head and neck cell lines screened through potent lytic activity, E1a and transgene expression. In vivo, in both ICI naive and refractory models, we observed improvement to tumor growth control and long-term survival when combining anti-PD-1 or anti-PD-L1 with the non-replicative adenovirus encoding mTNF alpha and mIL-2 compared to monotherapies. This observation was verified by striking CD3(+) TIL derived mGranzyme b and interferon gamma production complemented by increased T cell bioenergetics. Notably, interrogation of the tumor immune transcriptome revealed the upregulation of a gene signature distinctive of tertiary lymphoid structure formation upon treatment of murine anti-PD-L1 refractory tumors with non-replicative adenovirus encoding mTNF alpha and mIL-2. In addition, we detected an increase in anti-tumor antibody production and expansion of the memory T cell compartment in the secondary lymphoid organs. In summary, a non-replicative adenovirus encoding mTNF alpha and mIL-2 potentiates ICI therapy, demonstrated by improved tumor growth control and survival in head and neck tumor-bearing mice. Moreover, the data reveals a potential approach for inducing tertiary lymphoid structure formation. Altogether our results support the clinical potential of combining this adenovirotherapy with anti-PD-1 or anti-PD-L1.Peer reviewe

Adenovirus Encoding Tumor Necrosis Factor Alpha and Interleukin 2 Induces a Tertiary Lymphoid Structure Signature in Immune Checkpoint Inhibitor Refractory Head and Neck Cancer

Immune checkpoint inhibitors (ICI) have provided significant improvement in clinical outcomes for some patients with solid tumors. However, for patients with head and neck cancer, the response rate to ICI monotherapy remains low, leading to the exploration of combinatorial treatment strategies. In this preclinical study, we use an oncolytic adenovirus (Ad5/3) encoding hTNF alpha and hIL-2 and non-replicate adenoviruses (Ad5) encoding mTNF alpha and mIL-2 with ICI to achieve superior tumor growth control and improved survival outcomes. The in vitro effect of Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 was characterized through analyses of virus replication, transgene expression and lytic activity using head and neck cancer patient derived cell lines. Mouse models of ICI naive and refractory oral cavity squamous cell carcinoma were established to evaluate the local and systemic anti-tumor immune response upon ICI treatment with or without the non-replicative adenovirus encoding mTNF alpha and mIL-2. We delineated the mechanism of action by measuring the metabolic activity and effector function of CD3(+) tumor infiltrating lymphocytes (TIL) and transcriptomic profile of the CD45(+) tumor immune compartment. Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 demonstrated robust replicative capability in vitro across all head and neck cell lines screened through potent lytic activity, E1a and transgene expression. In vivo, in both ICI naive and refractory models, we observed improvement to tumor growth control and long-term survival when combining anti-PD-1 or anti-PD-L1 with the non-replicative adenovirus encoding mTNF alpha and mIL-2 compared to monotherapies. This observation was verified by striking CD3(+) TIL derived mGranzyme b and interferon gamma production complemented by increased T cell bioenergetics. Notably, interrogation of the tumor immune transcriptome revealed the upregulation of a gene signature distinctive of tertiary lymphoid structure formation upon treatment of murine anti-PD-L1 refractory tumors with non-replicative adenovirus encoding mTNF alpha and mIL-2. In addition, we detected an increase in anti-tumor antibody production and expansion of the memory T cell compartment in the secondary lymphoid organs. In summary, a non-replicative adenovirus encoding mTNF alpha and mIL-2 potentiates ICI therapy, demonstrated by improved tumor growth control and survival in head and neck tumor-bearing mice. Moreover, the data reveals a potential approach for inducing tertiary lymphoid structure formation. Altogether our results support the clinical potential of combining this adenovirotherapy with anti-PD-1 or anti-PD-L1.Peer reviewe