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Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8+ T cell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target.

Tiivistelmä. Entropialla on monta tulkintaa. Useimmiten entropian yhteydessä puhutaan, tavalla tai toisella, systeemin epäjärjestyksestä tai kaaoksesta. Tämä on luonteva tulkinta myöskin dynaamisen systeemin topologiselle entropialle, josta lähdemme liikkeelle tässä tekstissä. Tämän jälkeen etenemme entropiaan, joka on yhtenevä klassisen, termodynaamisen entropian määritelmän kanssa, ja tällöin oleellista on entropian tulkinta informaationa. Tämä kyseinen entropia määritellään avaruuden ositukselle, ja sen pohjalta määritellään lopulta mittateoreettinen entropia avaruuden dynamiikalle, joka jälleen oleellisesti liityy dynamiikan kaoottisuuteen. Eräs tärkeimmistä tuloksista tässä tekstissä on Kolmogorov-Sinai-lause, jonka avulla laskemme mittateoreettisen entropian konkreettisesti muutamalle tunnetulle, yksinkertaiselle dynaamiselle systeemille. Mittateoreettinen entropia on keskeinen käsite ergodisessa teoriassa ja siksi onkin luontevaa, että määrittelemme tässä tekstissä myös ergodisen kuvauksen käsitteen, sekä vertaamme toisiinsa entropiaa ja ergodisuutta. Lopuksi näytämme yhteyden topologisen entropian ja mittateoreettisen entropian välillä niin sanotun variaatioperiaatteen muodossa. Teksti pohjautuu pääosin kirjaan M. Brin, G. Stuck: “Introduction to Dynamical systems”. Toisena lähteenä on erään luentomonisteen ensimmäinen kappale: “Measure-Theoretic Entropy, Introduction”.

Purpose: This paper empirically demonstrates the major organizational events of a rolling forecasting process and the roles of controllers therein. In particular, this study aims to investigate how the understanding of a “realistic forecast” is translated and questioned by various mediators in the rolling forecasting process and how it affects the quality of planning as the ultimate accuracy of forecasts is seen as important. Design/methodology/approach: This study follows an actor-network theory (ANT) approach and maps the key points of translation in the rolling forecasting process by inspecting the roles of mediators. This qualitative case study is based on interviews with controllers and managers involved in the forecasting process in a single manufacturing company. Findings: The paper identified two episodes of translation in the forecasting process, in which the forecast partially stabilized to create room for managerial discussion and debate. The abilities of controllers to infiltrate various functional groups and calculative practices appeared to be one way to control the accuracy of forecasting, although this was built on a façade of neutrality. Originality/value: Prior literature identifies the aims of interactive planning processes as being to improve the quality of planning. The authors apply ANT to better understand the nature of mediators in constructing an entity called a “realistic rolling forecast”.

In Finland, many human-derived processes, including mining, municipal wastewater treatment, urban runoff, agriculture, forestry and peat extraction, lead to nitrogen and/or heavy metal loads to recipient water bodies. It is often not cost-effective to build active water treatment units for many of these operations. This is true e.g., for mining operations (especially after mine closure), municipalities producing small amounts of wastewater (e.g., in holiday resorts), urban runoffs, peat extraction and agriculture. When active treatment options are not economically feasible, passive treatment options (bioreactors, moss pools) in various combinations with active treatment can be used to treat the water in a cost-efficient manner. It is expected that the demand for passive treatment options will increase in the future, because the quality limits required in water purification are being tightened and there is a need for year-round control of contaminant load to recipient water bodies. In the TypArkt-project, the year-round monitoring of the hybrid purification systems built for the Pyhäsalmi mine in 2018 and in 2019 for the Kallo village wastewater treatment plant in Kittilä municipality has been continued to obtain longer-term performance data. In addition, the pilot structure designed for Levi’s stormwater treatment has been monitored, along with the mixed woodchip bioreactor built by the mine in October 2022 at the Kevitsa mine. Based on the results, target metals can be well removed in Pyhäsalmi in the hybrid purification system, when the last part of the hybrid purification unit, wetland is left out from the study. However, the wetland, and especially the root clumps of lake sediment brought there from a metal-contaminated area, cause an increase in the concentration of metals when the water flows through the wetland. In the hybrid purification structure of Kallo village’s wastewater treatment plant, nitrogen can be removed by an average of slightly more t, Tiivistelmä Suomessa ja erityisesti myös Suomen pohjoisosissa kylmissä olosuhteissa on monenlaista typpi ja/tai raskasmetallipitoista kuormitusta aiheuttavaa ihmistoimintaa, kuten kaivostoiminta ja jätevedenpuhdistamot. Erilaisia aktiivisia ja asianmukaisia vedenpuhdistusmenetelmiä on käytössä erityisesti toiminnassa olevilla kaivoksilla ja isoilla jätevedenpuhdistamoilla. Kustannusten vuoksi ei kaikkialle kuitenkaan ole järkevää rakentaa kokonaan aktiivista menetelmää vaan erilaiset passiivisten menetelmien (esim. bioreaktorit, sammalaltaat) sekä passiivisten ja aktiivisten menetelmien yhdistelmät voivat olla toimivia ratkaisuja esim. kaivosten jälkikäyttövaiheeseen, muutaman talon kyläyhteisön tai lomakylän jätevesienkäsittelyyn tai taajamien hulevesien käsittelyyn. Passiivisten puhdistusratkaisujen tarpeen ja kysynnän, yhdistettynä mahdollisesti aktiivisiin menetelmiin, odotetaan yhä kasvavan tulevaisuudessa, sillä vedenpuhdistukselle asetettavat vaatimukset tiukkenevat ja ympärivuotiselle kuormituksen hallinnalle on tarvetta. TypArkt-hankkeessa on jatkettu vuonna 2018 Pyhäsalmen kaivokselle ja vuonna 2019 Kittilän kunnan, Kallon kylän, jätevedenpuhdistamolle rakennettujen hybridipuhdistusratkaisujen ympärivuotista seurantaa pidempiaikaisen toimivuustiedon saamiseksi. Lisäksi on seurattu Levin hulevesien käsittelyyn suunniteltua pilottirakennetta, ja Kevitsan kaivokselle kaivoksen lokakuussa 2022 rakentamaa sekapuuhakebioreaktoria. Tulosten perusteella Pyhäsalmella saadaan hyvin poistettua tavoitemetalleja hybridipuhdistusrakenteessa, kun ei oteta huomioon hybridipuhdistusrakenteen viimeistä yksikköä, kosteikkoa. Kosteikko, ja erityisesti sinne metalleilla kontaminoituneelta alueelta tuodut järviruon juuripaakut, aiheuttavat kuitenkin metallien pitoisuuden lisääntymistä, kun vesi virtaa kosteikon läpi. Kallon kylän jätevedenpuhdistamon hybridipuhdistusrakenteessa saadaan typpeä poistumaan keskimäärin vähän yli 30 %, mikä on erittäin hyvä verrattuna lähtötilantees

We report the effect of the quantum dot aspect ratio on the sub-gap absorption properties of GaAs/AlGaAs quantum dot intermediate band solar cells. We have grown AlGaAs solar cells containing GaAs quantum dots made by droplet epitaxy. This technique allows the realization of strain-free nanostructures with lattice matched materials, enabling the possibility to tune the size, shape, and aspect ratio to engineer the optical and electrical properties of devices. Intermediate band solar cells have been grown with different dot aspect ratio, thus tuning the energy levels of the intermediate band. Here, we show how it is possible to tune the sub-gap absorption spectrum and the extraction of charge carriers from the intermediate band states by simply changing the aspect ratio of the dots. The tradeoff between thermal and optical extraction is in fact fundamental for the correct functioning of the intermediate band solar cells. The combination of the two effects makes the photonic extraction mechanism from the quantum dots increasingly dominant at room temperature, allowing for a reduction of the open circuit voltage of only 14 mV, compared to the reference cell.

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients

BACKGROUND: Open prostatectomy (OP) and transurethral resection of the prostate (TURP) have traditionally been the most common surgical approaches for the treatment of benign prostatic hyperplasia causing bladder outlet obstruction and have certainly passed the test of time. In time, many endoscopic surgical procedures have been described as an alternative mini-invasive treatment. Holmium laser enucleation (HoLEP) guaranteed functional outcomes similar to OP and TURP with lower perioperative complication rates for any prostate size. With the development of different kinds of lasers (such as thulium, "green light" and diode) and bipolar energy, the feasibility of endoscopic enucleation using these energies has been explored. EVIDENCE ACQUISITION: In this paper, recent techniques to perform true prostate enucleation have been reviewed through a search of PubMed and Web of Science, including articles published in the last 20 years in clinical journals. The review is based on a peer-review process of the authors after a structured data search. Search terms included "Thulium prostate enucleation, THULEP, TmLEP/Tm Yag enucleation" OR "Greenlight enucleation/prostate enucleation/vapoenucleation/ KTP prostate enucleation, PVP prostate enucleation, GreenLep/" OR "bipolar prostate enucleation" OR "HoLEP, Holmium prostate enucleation" OR "monopolar prostate enucleation" OR "Diode prostate enucleation" OR "DiLEP" OR "Eraser prostate enucleation" OR "ELEP". EVIDENCE SYNTHESIS: Following the example of HoLEP, many techniques have been described in the literature using a variety of energy sources and instruments either in a pure enucleative or a hybrid (mixed) fashion. However, the levels of evidence are too low and follow-up still too short to offer solid recommendations. CONCLUSIONS: HoLEP has become the conceptual and practical paradigm for the wide spread of enucleation thanks to the evidence provided by the literature and excellent outcomes. Higher level of evidence is requir, BACKGROUND: Open prostatectomy (OP) and transurethral resection of the prostate (TURP) have traditionally been the most common surgical approaches for the treatment of benign prostatic hyperplasia causing bladder outlet obstruction and have certainly passed the test of time. In time, many endoscopic surgical procedures have been described as an alternative mini-invasive treatment. Holmium laser enucleation (HoLEP) guaranteed functional outcomes similar to OP and TURP with lower perioperative complication rates for any prostate size. With the development of different kinds of lasers (such as thulium, "green light" and diode) and bipolar energy, the feasibility of endoscopic enucleation using these energies has been explored. EVIDENCE ACQUISITION: In this paper, recent techniques to perform true prostate enucleation have been reviewed through a search of PubMed and Web of Science, including articles published in the last 20 years in clinical journals. The review is based on a peer-review process of the authors after a structured data search. Search terms included "Thulium prostate enucleation, THULEP, TmLEP/Tm Yag enucleation" OR "Greenlight enucleation/prostate enucleation/vapoenucleation/ KTP prostate enucleation, PVP prostate enucleation, GreenLep/" OR "bipolar prostate enucleation" OR "HoLEP, Holmium prostate enucleation" OR "monopolar prostate enucleation" OR "Diode prostate enucleation" OR "DiLEP" OR "Eraser prostate enucleation" OR "ELEP". EVIDENCE SYNTHESIS: Following the example of HoLEP, many techniques have been described in the literature using a variety of energy sources and instruments either in a pure enucleative or a hybrid (mixed) fashion. However, the levels of evidence are too low and follow-up still too short to offer solid recommendations. CONCLUSIONS: HoLEP has become the conceptual and practical paradigm for the wide spread of enucleation thanks to the evidence provided by the literature and excellent outcomes. Higher level of evidence is requir

INTRODUCTION: To compare 2-year safety and efficacy outcomes after Aquablation or transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms related to benign prostate hyperplasia (BPH). METHODS: One hundred eighty-one patients with BPH were assigned at random (2:1 ratio) to either Aquablation or TURP. Patients and follow-up assessors were blinded to treatment. Assessments included the International Prostate Symptom Score (IPSS), Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function and uroflow. The focus of analysis was 2-year outcomes. RESULTS: At 2 years, IPSS scores improved by 14.7 points in the Aquablation group and 14.9 points in TURP (p = .8304, 95% CI for difference - 2.1 to 2.6 points). Two-year improvements in maximum flow rate (Qmax) were large in both groups at 11.2 and 8.6 cc/s for Aquablation and TURP, respectively (p = 0.1880, 95% CI for difference - 1.3 to 6.4). Sexual function as assessed by MSHQ was stable in the Aquablation group and decreased slightly in the TURP group. At 2 years, PSA was reduced significantly in both groups by 0.7 and 1.2 points, respectively; the reduction was similar across groups (p = 0.1816). Surgical retreatment rates after 12 months for Aquablation were 1.7% and 0% for TURP. Over 2 years, surgical BPH retreatment rates were 4.3% and 1.5% (p = 0.4219), respectively. CONCLUSION: Two-year efficacy outcomes after TURP and Aquablation were similar, and the rate of surgical retreatment was low and similar to TURP. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT02505919. FUNDING: PROCEPT BioRobotics.

OBJECTIVE: To test the hypothesis that benign prostatic hyperplasia (BPH) robotic surgery with aquablation would have a more pronounced benefit in certain patient subgroups, such as men with more challenging anatomies (e.g. large prostates, large middle lobes) and men with moderate BPH. METHODS: We conducted prespecified and post hoc exploratory subgroup analyses from a double-blind, multicentre prospective randomized controlled trial that compared transurethral resection of the prostate (TURP) using either standard electrocautery vs surgery using robotic waterjet (aquablation) to determine whether certain baseline factors predicted more marked responses after aquablation as compared with TURP. The primary efficacy endpoint was reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo persistent grade 1 or grade ≥2 surgical complications. RESULTS: For men with larger prostates (50-80 g), the mean IPSS reduction was four points greater after aquablation than after TURP (P = 0.001), a larger difference than the overall result (1.8 points; P = 0.135). Similarly, the primary safety endpoint difference (20% vs 46% [26% difference]; P = 0.008) was greater for men with large prostate compared with the overall result (26% vs 42% [16% difference]; P = 0.015). Postoperative anejaculation was also less common after aquablation compared with TURP in sexually active men with large prostates (2% vs 41%; P < 0.001) vs the overall results (10% vs 36%; P < 0.001). Exploratory analysis showed larger IPSS changes after aquablation in men with enlarged middle lobes, men with severe middle lobe obstruction, men with a low baseline maximum urinary flow rate, and men with elevated (>100) post-void residual urine volume. CONCLUSIONS: In men with moderate-to-severe lower urinary tract symptoms attributable to BPH and larger, more complex prostates, aquablation was associated with both superior symptom score improvem

We present a completely explicit transcendence measure for e. This is a continuation and an improvement to the works of Borel, Mahler, and Hata on the topic. Furthermore, we also prove a transcendence measure for an arbitrary positive integer power of e. The results are based on Hermite–Padé approximations and on careful analysis of common factors in the footsteps of Hata.

Tiivistelmä. Tarkoitus: Tämän kirjallisuuskatsauksena toteutetun tutkimuksen tarkoituksena on kuvailla koulu- ja opiskeluterveydenhuollon palveluiden saatavuuden ja saavutettavuuden parantamista kansainvälisen tutkimustiedon perusteella. Aineisto ja menetelmät: Aineiston keruu toteutettiin tietokantahakuna Medic-, CINAHL-, ProQuest-, Scopus- ja PubMed-tietokantoihin. Aineisto koostuu 25 kansainvälisestä tieteellisessä lehdessä julkaistusta vertaisarvioidusta alkuperäistutkimuksesta. Kyseessä on narratiivinen kirjallisuuskatsaus. Aineisto analysoitiin sisällönanalyysin periaatteita soveltaen. Tulokset: Monialainen koulun, terveydenhuollon ja oppilaan tai opiskelijan sekä perheen tiivis yhteistyö on monin tavoin hyödyllistä, kuin myös terveyspalveluita tarjoavien toimijoiden keskinäinen verkostoituminen ja yhteistyö. Kouluterveydenhoitajalta odotetaan hoidon koordinaattorina toimimista. Hyvän saavutettavuuden näkökulmasta palveluiden tulisi olla koulun yhteydessä. Eri terveyspalvelut voivat olla yhdistettynä koulun yhteydessä sijaitseviin kouluterveyskeskuksiin. Henkilöstön vastuita voidaan jakaa uudelleen siirtäen rutiinitehtäviä hoitajilta ja lääkäreiltä avustavalle henkilökunnalle. Etäyhteyden hyödyntäminen ja päällekkäiset aikojen varaukset voivat myös parantaa palveluiden saatavuutta ja saavutettavuutta. Saatavuutta ja saavutettavuutta voidaan parantaa toisaalta myös tarjoamalla enemmän ilman ajanvarausta toimivaa vastaanottoa. Asiakkaan yksityisyys on oltava turvattuna, kun ja jotta hän hakeutuu palveluihin. Palvelun sisältöä voidaan parantaa vastaamaan tarpeisiin kouluttamalla henkilöstöä kulttuurien erityispiirteistä, seksuaalisuuden ja sukupuolen moninaisuudesta sekä erityislasten kompleksisista terveydellisistä tarpeista. Palveluiden sisältöä on tärkeää markkinoida näkyvämmin. Johtopäätökset: Kansainvälistä koulu- ja opiskeluterveydenhuollon saatavuuden ja saavutettavuuden parantamisen tutkimustietoa voidaan hyödyntää koulu- ja opiskeluterveydenhuollon palve