Abstract
All jurisdictions assume a concept of an act of a sexual nature by regulating sex crimes. Until the sex revolution and feminist movements for equality in sexual relations, criminal law was ...mostly concerned with specific types of sexual acts, particularly non-marital sexual intercourse. With the paradigm shift of recent years, criminalization tends to embrace all acts of a sexual nature with another person without her valid consent. Whether the law contains a definition of a sexual act or not, borderline cases show that neither merely objective criteria nor purely subjective elements can serve as basis for the description of the conduct under prohibition. Our Article tries to overcome this deficit in the criminal law theory. Sexual acts should not be understood through the metaphor of a “picture,” as German legal scholars believe, but with the metaphor of a script played out by an actor as sexual theorists put it.
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NUK, ODKLJ, PRFLJ, UL, UM, UPUK
The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA ...SIOP-RTSG 2016 (the UMBRELLA protocol), to continue international collaboration in the treatment of childhood renal tumours. This protocol will support integrated biomarker and imaging research, focussing on assessing the independent prognostic value of genomic changes within the tumour and the volume of the blastemal component that survives preoperative chemotherapy. Treatment guidelines for Wilms tumours in the UMBRELLA protocol include recommendations for localized, metastatic, and bilateral disease, for all age groups, and for relapsed disease. These recommendations have been established by a multidisciplinary panel of leading experts on renal tumours within the SIOP-RTSG. The UMBRELLA protocol should promote international collaboration and research and serve as the SIOP-RTSG best available treatment standard.
According to investigations in phytomedicine and ethnopharmacology, the therapeutic properties of garlic (Allium sativum) have been described by ancestral cultures. Notwithstanding, it is of ...particular concern to elucidate the molecular mechanisms underlying this millenary empirical knowledge. Allicin (S-allyl prop-2-ene-1-sulfinothioate), a thioester of sulfenic acid, is one of the main bioactive compounds present in garlic, and it is responsible for the particular aroma of the spice. The pharmacological attributes of allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others). The primary goal of the present article is to review and clarify the common molecular mechanisms by which allicin and its derivates molecules may perform its therapeutic effects on cardiovascular diseases and neuroinflammatory processes. The intricate interface connecting the cardiovascular and nervous systems suggests that the impairment of one organ could contribute to the dysfunction of the other. Allicin might target the cornerstone of the pathological processes underlying cardiovascular and neuroinflammatory disorders, like inflammation, renin-angiotensin-aldosterone system (RAAS) hyperactivation, oxidative stress, and mitochondrial dysfunction. Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes. Finally, allicin represents an attractive therapeutic alternative targeting the complex interaction between cardiovascular and neuroinflammatory disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background Before this study started, the standard postoperative chemotherapy regimen for stage II–III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, ...avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II–III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. Methods For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II–III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m2 at weeks 1–8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m2 given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. Findings Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8–79·8). 2 year event-free survival was 92·6% (95% CI 89·6–95·7) for treatment including doxorubicin and 88·2% (84·5–92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4–9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3–98·8) for treatment including doxorubicin and 95·8% (93·3–98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence. Interpretation Doxorubicin does not need to be included in treatment of stage II–III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification. Funding See Acknowledgments for funders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Metal ions are the common pollutants in the aquatic environment, harmful to living organisms, non-biodegradable, and toxic even at low concentrations, thus, the present study aimed theoretically ...evaluate the potential for interaction of Fe
2+
, Co
2+
, Ni
2+
, Cu
2+
, Zn
2+
, Pb
2+
, and Cr
3+
metal ions potentially toxic with B
12
N
12
nanocage. The location of the possible interaction sites was initially assessed by the Frontier Molecular Orbitals (FMOs), Molecular Electrostatic Potential, atomic charges NPA and the analysis allowed to predict the possible interaction sites. The results show that for ions with unpaired electrons in the valence shell, the interaction can occur on the boron atom or on the nitrogen atom. The interaction of the metal ions in the six-atom ring B–N–B–N–B–N is also possible, and site of interaction presented the longest bond lengths, > 3.2 Å. The calculations of the energies involved in the processes, binding energy (
E
Bind
), Gibbs and enthalpy proved that the interaction of the metal cations with the B
12
N
12
nanocage is almost all spontaneously and follows the order: Zn
2+
> Ni
2+
> Cu
2+
> Cr
3+
> Co
2+
> Fe
2+
> Pb
2+
. The Quantum Theory of Atoms in Molecule (QTAIM) was used to determine the nature of the interaction between the metal ions and the nanocage showing that interactions are non-covalent or partially covalent. Finally, the results from NPA charge after the interaction showed that the direction of charge transfer is from metal ions to the nanocage.
Graphic abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms ...tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence.
Methods
Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) registries and the SIOP‐RTSG network (1989‐2019). Events were defined as relapse, metachronous tumors, or death.
Results
Forty‐three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6‐44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5‐year event‐free survival rate was 84.3% (95% confidence interval, 72.4%‐98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%‐100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1).
Conclusions
Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised.
Lay Summary
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor.
In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) and the SIOP‐RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur.
Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised.
Patients with WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) and Wilms tumor/nephroblastomatosis, identified through the International Society of Pediatric Oncology Renal Tumor Study Group registries and network, have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing Wilms tumor protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Belgium had a long tradition of direct informal employment in paid domestic work, which has undergone formalisation through the introduction of the ‘service voucher system’. This policy triangulates ...the employment relationship between workers and clients through introducing third-party employing agencies, and guarantees workers’ access to labour and social security rights. Up until now, most international studies of paid domestic work have focused on direct and privatized worker-employer relationships (Anderson, Doing the dirty work?: The global politics of domestic labour, 2000); Hondagneu-Sotelo, Domestica: Immigrant workers cleaning and caring in the shadows of affluence, 2001); (Lutz, The New Maids: Transnational women and the care economy, 2011); Moras (Sociology Mind, 3(3), 248–256, 2013); (Romero, Maid in the U.S.A., 1992). This literature has shown that paid domestic work often features ‘personalised’ (emotionally-loaded) worker-employer relationships. The goal of this article is to analyse the impact of the introduction of the service voucher system on personalisation processes affecting paid domestic work in Belgium. Is personalisation bound to disappear with the sector’s formalisation or is it intrinsic to paid domestic work?
We show that personalisation is not threatened by formalisation policies which do not challenge the structural inequalities underpinning paid domestic work (and to which personalisation develops as a remedy). In the Belgian case, the service voucher policy did not challenge the crucial role of personalisation for finding and keeping jobs, as well as improving working conditions. The article shows that personalisation is an informal social protection strategy which developed in the exploitative conditions of informality, but is likely to survive formalising policies. Indeed, formalisation did not eliminate the need for personalisation, as it did not substantially improve working conditions in the sector, failed to recognise workers’ qualifications and to challenge the gendered and migrantized character of domestic work employment.
Bone cancers occur frequently in children, adolescents, and young adults aging 15 to 29 years. Osteosarcoma and Ewing sarcoma are the most frequent subtypes in this population. The aim of this study ...was to describe incidence and mortality trends of bone cancers among Brazilian children, adolescents and young adults.
Incidence information was obtained from 23 population-based cancer registries. Mortality data were extracted from the Atlas of Cancer Mortality from 1979 to 2013. Specific and adjusted rates per million were analyzed according to gender, morphology and age at diagnosis. Median rates were used as a measure of central tendency. Joinpoint regression was applied to analyze trends.
Median incidence rates were 5.74 and 11.25 cases per million in children and young adults respectively. Osteosarcoma in the 15-19 years aged group had the highest incidence rates. Stable incidence rates were observed among five registries in 0-14 year's age group. Four registries had a decreased incidence trend among adolescents and young adults. Median mortality rates were 1.22 and 5.07 deaths per million in children and young adults respectively. Increased mortality was observed on the North and Northeast regions. Decreased mortality trends were seen in the South (children) and Southeast (adolescents and young adults).
Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
More than one in four Brazilians have private health insurance (PHI), even thought it covers mostly the same procedures as the Brazilian Unified National Health System (SUS). This literature review ...included articles and monographs published since 1990 about the utilization of SUS by privately insured individuals. Considering outpatient care and hospitalization, privately insured people in Brazil use SUS in approximately 13% of the times they receive health care, and approximately 7% of people receiving care paid by SUS are privately insured; these findings vary depending on the type of service studied and on study methods. Utilization of SUS is more frequent in less developed regions, by people with more restricted PHI plans and by people with worse health status. Privately insured people report the limitations of PHI plans as their reasons for resorting to SUS. Sometimes, beneficiaries of PHI plans owned by nonprofit hospitals (which also provide health care financed by SUS) have easier access to care than uninsured people financed by SUS. Anecdotally, privately insured people are satisfied with SUS, but not to the point of adopting SUS as their preferred source of care. In short, for privately insured people, SUS only plays a secondary role in their health care. Despite PHI taking over part of the SUS's health care demand, PHI represents a restriction of the universal, equitable character of the SUS.
Outcomes are excellent for the majority of patients with Wilms tumors (WT). However, there remain WT subgroups for which the survival rate is approximately 50% or lower. Acknowledging that the ...composition of this high‐risk group has changed over time reflecting improvements in therapy, we introduce the authors’ view of the historical and current approach to the classification and treatment of high‐risk WT. For this review, we consider high‐risk WT to include patients with newly diagnosed metastatic blastemal‐type or diffuse anaplastic histology, those who relapse after having been initially treated with three or more different chemotherapeutics, or those who relapse more than once. In certain low‐ or low middle‐income settings, socio‐economic factors expand the definition of what constitutes a high‐risk WT. As conventional therapies are inadequate to cure the majority of high‐risk WT patients, advancement of laboratory and early‐phase clinical investigations to identify active agents is urgently needed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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