Halo observations provide evidence of airborne cubic ice in the Earth’s atmosphere

An ice crystal halo display that contains several previously unknown halo phenomena was observed in Northern Chile. Analysis of computer simulations of the halos demonstrates that most of the new halo arcs in the display can be explained by the presence of airborne and preferentially oriented crystals of cubic ice. These observations therefore provide evidence of the existence of the cubic phase of ice in the Earth's atmosphere

Robot-assisted versus three-dimensional laparoscopic radical prostatectomy : 12-month outcomes of a randomised controlled trial

Objectives: To compare functional and oncological outcomes of robot-assisted laparoscopic prostatectomy (RALP) to three-dimensional laparoscopic radical prostatectomy (3D-LRP) at 12 months after surgery. Patients and methods: Prospective randomised single-centre study of 145 consecutive men referred to radical prostatectomy in a tertiary referral centre in Finland. Patients were randomised 1:1 to the RALP (N = 75) and 3D-LRP (N = 70) groups. The primary outcome was urinary continence evaluated with the Expanded Prostate Cancer Index Composite 26-item version (EPIC-26) incontinence domain score at 12 months after surgery. Secondary outcomes included the use of protective pads at 12 months after surgery, EPIC-26 domain scores of irritative/obstructive, bowel, sexual and hormonal symptoms, positive surgical margin (PSM) rate, and biochemical recurrence (BCR). Complication frequency within the 3-month period after surgery was evaluated according to Clavien–Dindo classification. Statistical significance between groups was analysed using Mann–Whitney, chi-square and Fisher's exact tests. The trial was terminated after interim analysis based on no statistically significant difference in EPIC-26 urinary incontinence domain scores. Altogether 145 patients of the target accrual of 280 patients were recruited. Results: Postoperative continence at 12 months after surgery according to the EPIC-26 incontinence domain was 79.25 in both groups (P = 0.4). Between group difference was −5.8 (95% confidence interval –15.2 to 3.6). There was no statistically significant difference in the rates of PSM or BCR between the two surgical modality groups. Conclusion: We were unable to demonstrate a difference between the RALP and 3D-LRP groups for functional and oncological outcomes at 12 months after surgery.Peer reviewe

Kelan monimuotoisen perhekuntoutuksen kehittämistyö : Palveluntuottajien näkökulma

Kelan Lasten perhekuntoutuksen kehittämishankkeissa (LAKU- ja Etä-LAKU-hankkeet) on kehitetty monimuotoista perhekuntoutusta 5–12-vuotiaille lapsille ja heidän perheilleen. Kehittämistyötä on toteutettu vuosina 2012–2018, minkä jälkeen kuntoutuspalvelu jalkautetaan soveltuvin osin Kelan valtakunnalliseen kuntoutustoimintaan. Kehittämistyön aikana on saatu paljon arvokasta tietoa niin asiakkailta, palveluntuottajilta kuin yhteistyökumppaneiltakin. Tieteellisen seurantatutkimuksen keskeiset tulokset julkaistaan erillisessä raportissa. Tässä raportissa kuvataan lyhyesti hankkeen taustaa sekä kuntoutuksen sisältöä. Pääpaino on kuitenkin palveluntuottajien kirjoittamissa teksteissä, jossa he kuvaavat omin sanoin työryhmän, asiakkaiden sekä yhteistyötahojen kokemuksia LAKU- ja Etä-LAKU-kuntoutuksesta. Lapsen kuntoutuksessa on tärkeää ottaa mukaan koko perhe sekä arjen toimintaympäristö, kuten koulu ja päiväkoti. Tämä mahdollistui LAKU-kuntoutuksessa. Yhteistyö hoitavan tahon kanssa oli joissakin tapauksissa haasteellista mm. aikataulujen suhteen, mutta toteutui pääasiassa hyvin. Kuntoutus sisältää joustavuutta niin käyntikertojen rakenteessa kuin sisällössäkin. Sitä toivottiin kuitenkin jatkossa lisää, koska perheiden haasteet ovat erilaisia. LAKU- ja Etä-LAKU-kuntoutukseen kuuluivat perheiden kuntoutusviikonloput, joita pidettiin toimivina. Niissä korostui erilaiset ryhmätoiminnat sekä erityisesti vertaistuki. Asiakkaat toivoivat enemmän kuin kaksi viikonloppua kuntoutusprosessin aikana, mutta palveluntuottajien näkemyksen mukaan määrä oli riittävä. Etä-LAKU-hankkeessa kuntoutus tapahtui pääasiassa perheen kotona niillä paikkakunnilla, joissa etäisyydet ovat pitkiä ja palveluita vähän. Malli haastoi työntekijät, mutta myös antoi paljon. Perheet olivat tyytyväisiä ja hyvin sitoutuneita kotona tehtävään kuntoutukseen. Asiakasperheet, yhteistyökumppanit että työntekijät kokivat LAKU- ja Etä-LAKU-kuntoutuksen pää-sääntöisesti hyödylliseksi ja lapsen sekä perheen toimintakykyä parantavaksi kuntoutusmuodoksi. Yhtenäisenä toiveena oli, että kuntoutus jatkuisi Kelan vakiintuneena toimintana hankkeiden jälkeen

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy : study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting. This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanrnaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.Peer reviewe

Discovery and development of ODM-204: A Novel nonsteroidal compound for the treatment of castration-resistant prostate cancer by blocking the androgen receptor and inhibiting CYP17A1

We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form of prostate cancer characterised by high androgen receptor (AR) expression and persistent activation of the AR signaling axis by residual tissue androgens. For ODM-204, has a dual mechanism of action. The compound is anticipated to efficiently dampen androgenic stimuli in the body by inhibiting CYP17A1, the prerequisite enzyme for the formation of dihydrotestosterone (DHT) and testosterone (T), and by blocking AR with high affinity and specificity. In our study, ODM-204 inhibited the proliferation of androgen-dependent VCaP and LNCaP cells in vitro and reduced significantly tumour growth in a murine VCaP xenograft model in vivo. Intriguingly, after a single oral dose of 10-30 mg/kg, ODM-204 dose-dependently inhibited adrenal and testicular steroid production in sexually mature male cynomolgus monkeys. Similar results were obtained in human chorionic gonadotropin-treated male rats. In rats, leuprolide acetate-mediated (LHRH agonist) suppression of the circulating testosterone levels and decrease in weights of androgen-sensitive organs was significantly and dose-dependently potentiated by the co-administration of ODM-204. ODM-204 was well tolerated in both rodents and primates. Based on our data, ODM-204 could provide an effective therapeutic option for men with CRPC.</p

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins’ efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT.Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial.Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.</p

Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension

Background: It remains unclear whether patients with positive surgical margins or extracapsular extension benefit from adjuvant radiotherapy following radical prostatectomy. Objective: To compare the effectiveness and tolerability of adjuvant radiotherapy following radical prostatectomy. Design, setting, and participants: This was a randomised, open-label, parallel-group trial. A total of 250 patients were enrolled between April 2004 and October 2012 in eight Finnish hospitals, with pT2 with positive margins or pT3a, pN0, M0 cancer without seminal vesicle invasion. Intervention: A total of 126 patients received adjuvant radiotherapy at 66.6 Gy. Outcome measurements and statistical analysis: The primary endpoint was biochemical recurrence-free survival, which we analysed using the Kaplan-Meier method and Cox proportional hazard regression. Overall survival, cancer-specific survival, local recurrence, and adverse events were secondary endpoints. Results and limitations: The median follow-up time for patients who were alive when the follow-up ended was 9.3 yr in the adjuvant group and 8.6 yr in the observation group. The 10-yr survival for biochemical recurrence was 82% in the adjuvant group and 61% in the observation group (hazard ratio [HR] 0.26 [95% confidence interval {CI} 0.14-0.48], p <0.001), and for overall survival 92% and 87%, respectively (HR 0.69 [95% CI 0.29-1.60], p = 0.4). Two and four metastatic cancers occurred, respectively. Out of the 43 patients with biochemical recurrence in the observation group, 37 patients received salvage radiotherapy. In the adjuvant group, 56% experienced grade 3 adverse events, versus 40% in the observation group (p = 0.016). Only one grade 4 adverse event occurred (adjuvant group). A limitation of this study was the number of patients. Conclusions: Adjuvant radiotherapy following radical prostatectomy is generally well tolerated and prolongs biochemical recurrence-free survival compared with radical prostatectomy alone in patients with positive margins or extracapsular extension. Patient summary: Radiotherapy given immediately after prostate cancer surgery prolongs prostate-specific antigen progression-free survival, but causes more adverse events, when compared with surgery alone. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

Length of prostate biopsies is not necessarily compromised by pooling multiple cores in one paraffin block: an observational study

Background Individually submitted prostatic needle biopsies are recommended by most guidelines because of their potential advantage in terms of core quality. However, unspecified bilateral biopsies are commonly submitted in many centers. The length of the core is the key quality indicator of prostate biopsies. Because there are few recent publications comparing the quality of 12 site-designated biopsies versus pooled biopsies, we compared the lengths of the biopsies obtained by both methods. Methods The material was obtained from 471 consecutive subjects who underwent prostatic needle biopsy in the Tampere University Hospital district between January and June 2013. Biopsies from 344 subjects fulfilled the inclusion criteria. The total number of cores obtained was 4047. The core lengths were measured on microscope slides. Extraprostatic tissue was subtracted from the core length. Results The aggregate lengths observed were 129.5 ± 21.8 mm (mean ± SD) for site-designated cores and 136.9 ± 26.4 mm for pooled cores (p = 0.09). The length of the core was 10.8 ± 1.8 mm for site-designated cores and 11.4 ± 2.2 mm for pooled cores (p = 0.87). The median length for pooled cores was 11 mm (range 5 mm – 18 mm). For individual site-designated cores, the median length was 11 mm (range 7 mm −15 mm). The core length was not correlated with the number of cores embedded into one paraffin block (r = 0.015). There was no significant difference in cancer detection rate (p = 0.62). Conclusions Our results suggest that unspecified bilateral biopsies do not automatically lead to reduced core length. We conclude that carefully embedded multiple (three to nine) cores per block may yield cores of equal quality in a more cost-efficient way and that current guidelines favoring individually submitted cores may be too strict.BioMed Central open acces