Evaluation Methodologies in Software Protection Research

Man-at-the-end (MATE) attackers have full control over the system on which the attacked software runs, and try to break the confidentiality or integrity of assets embedded in the software. Both companies and malware authors want to prevent such attacks. This has driven an arms race between attackers and defenders, resulting in a plethora of different protection and analysis methods. However, it remains difficult to measure the strength of protections because MATE attackers can reach their goals in many different ways and a universally accepted evaluation methodology does not exist. This survey systematically reviews the evaluation methodologies of papers on obfuscation, a major class of protections against MATE attacks. For 572 papers, we collected 113 aspects of their evaluation methodologies, ranging from sample set types and sizes, over sample treatment, to performed measurements. We provide detailed insights into how the academic state of the art evaluates both the protections and analyses thereon. In summary, there is a clear need for better evaluation methodologies. We identify nine challenges for software protection evaluations, which represent threats to the validity, reproducibility, and interpretation of research results in the context of MATE attacks

Discrimination, narratives and family history: an experiment with Jordanian host and Syrian refugee children

We measure the prevalence of discrimination between Jordanian host and Syrian refugee children attending school in Jordan. Using a simple sharing experiment, we find only little discrimination. Among the Jordanian children, however, we see that those who descended from Palestinian refugees do not discriminate at all, suggesting that a family history of refugee status can generate solidarity with new refugees. We also find that parents' narratives about the refugee crisis are correlated with the degree of discrimination, suggesting that discriminatory preferences are being transmitted through parental attitudes

The role of an advanced practice midwife in perinatal mental health: Outlining the process of role development and implementation

INTRODUCTION Perinatal mental health disorders (PMDs) are a global health concern. In industrialized countries, the prevalence of PMDs is estimated to be 20%, and they are associated with serious negative effects for women, their children and their families, along with high societal costs related to long-term impacts. In Switzerland, the PMD detection rate during obstetrical healthcare provision is very low (1–3%), and specialized healthcare services are limited. This study aimed to develop and implement an advanced practice midwife (APM) role at a Swiss obstetrics and gynecology hospital using the PEPPA framework to provide adequate screening and first-consultation services. METHODS The study uses a qualitative approach and follows the research stages using the 8-step from the participatory, evidence-based, patient-focused process for advanced practice nursing role development, implementation and evaluation (PEPPA) framework to develop and implement the APM role. RESULTS Utilizing the PEPPA framework, we were able to develop, implement, and evaluate the APM role in the field of perinatal mental health. Through appropriate screening and first-consultation services, we were able to identify affected women early and facilitate treatment. CONCLUSIONS In addition to stakeholder engagement and interprofessional collaboration, PEPPA serves as a beneficial framework for the process of role development, implementation, and evaluation in the midwifery profession. This study aims to assist midwives with Master's degrees in establishing corresponding roles within their practice areas, thereby enhancing care delivery. Furthermore, the current APM approach is intended to be continuously evaluated to gain new insights into its effectiveness

Residue concentrations of cloxacillin in milk after intramammary dry cow treatment considering dry period length

Dry cow treatment with an intramammary antibiotic is recommended to reduce the risk of mastitis at the beginning of the next lactation. The dry period may be shortened unintentionally, affecting antibiotic residue depletion and the time when residues reach concentrations below the maximum residue limit (MRL). The objective of this study was to evaluate residue depletion in milk after dry cow treatment with cloxacillin, considering dry periods of 14 (G14d), 21 (G21d), and 28 d (G28d). Overall, fifteen cows with 60 udder quarters were included in the study. For each cow, three of the udder quarters were treated with 1000 mg cloxacillin benzathine (2:1) on d 252, d 259, and d 266 of gestation; one quarter was left untreated. Milk samples were drawn until 20 DIM and milk composition, somatic cell count and cloxacillin residues were analyzed. The HPLC-MS/MS revealed different excretion kinetics for the compounds cloxacillin and cloxacillin benzathine (1:1). All cows showed a cloxacillin and cloxacillin benzathine (1:1) concentration below the MRL of 30 µg/kg after 5 d. In the udder quarters of G21d and G28d, the cloxacillin concentration was already below the MRL at first milking after calving. The cloxacillin benzathine (1:1) concentration in the milk of G28d, G21d, and G14d fell below 30 µg/kg on the 5th, 3rd, and 5th DIM, respectively. Shortening the dry period affects residue depletion after dry cow treatment with cloxacillin. The risk of exceeding the MRL, however, seems low, even with dry periods shorter than 14 d

Medical futility regarding cardiopulmonary resuscitation in in-hospital cardiac arrests of adult patients: A Systematic Review and Meta-analysis

For some patients, survival with good neurologic function after cardiopulmonary resuscitation (CPR) is highly unlikely, thus CPR would be considered medically futile. Yet, in clinical practice, there are no well-established criteria, guidelines or measures to determine futility. We aimed to investigate how medical futility for CPR in adult patients is defined, measured, and associated with do-not-resuscitate (DNR) code status as well as to evaluate through meta-analysis the predictive value of clinical risk scores.; We searched Embase, PubMed, CINAHL, and PsycINFO from the inception of each database up to January 22, 2021. Data were pooled using a fixed-effects model. Data collection and reporting followed the PRISMA guidelines.; Thirty-one studies were included in the systematic review and 11 in the meta-analysis. Medical futility defined by risk scores was associated with a significantly higher risk of in-hospital mortality (5 studies, 3102 participants with Pre-Arrest Morbidity (PAM) and Prognosis After Resuscitation (PAR) score; overall RR 3.38 [95% CI 1.92-5.97]) and poor neurologic outcome/in-hospital mortality (6 studies, 115213 participants with Good Outcome Following Attempted Resuscitation (GO-FAR) and Prediction of Outcome for In-Hospital Cardiac Arrest (PIHCA) score; RR 6.93 [95% CI 6.43-7.47]). All showed high specificity (>90%) for identifying patients with poor outcome.; There is no international consensus and a lack of specific definitions of CPR futility in adult patients. Clinical risk scores might aid decision-making when CPR is assumed to be futile. Future studies are needed to assess their clinical value and reliability as a measure of futility regarding CPR

Predicting neurological outcome in adult patients with cardiac arrest: systematic review and meta-analysis of prediction model performance

This work aims to assess the performance of two post-arrest (out-of-hospital cardiac arrest, OHCA, and cardiac arrest hospital prognosis, CAHP) and one pre-arrest (good outcome following attempted resuscitation, GO-FAR) prediction model for the prognostication of neurological outcome after cardiac arrest in a systematic review and meta-analysis. A systematic search was conducted in Embase, Medline, and Web of Science Core Collection from November 2006 to December 2021, and by forward citation tracking of key score publications. The search identified 1'021 records, of which 25 studies with a total of 124'168 patients were included in the review. A random-effects meta-analysis of C-statistics and overall calibration (total observed vs. expected [O:E] ratio) was conducted. Discriminatory performance was good for the OHCA (summary C-statistic: 0.83 [95% CI 0.81-0.85], 16 cohorts) and CAHP score (summary C-statistic: 0.84 [95% CI 0.82-0.87], 14 cohorts) and acceptable for the GO-FAR score (summary C-statistic: 0.78 [95% CI 0.72-0.84], five cohorts). Overall calibration was good for the OHCA (total O:E ratio: 0.78 [95% CI 0.67-0.92], nine cohorts) and the CAHP score (total O:E ratio: 0.78 [95% CI 0.72-0.84], nine cohorts) with an overestimation of poor outcome. Overall calibration of the GO-FAR score was poor with an underestimation of good outcome (total O:E ratio: 1.62 [95% CI 1.28-2.04], five cohorts). Two post-arrest scores showed good prognostic accuracy for predicting neurological outcome after cardiac arrest and may support early discussions about goals-of-care and therapeutic planning on the intensive care unit. A pre-arrest score showed acceptable prognostic accuracy and may support code status discussions

PLCζ is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLC zeta has been proposed as the physiological agent that triggers the Ca2+ oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLC zeta induces Ca2+ oscillations in eggs and debilitating mutations in the PLCZ1 gene are associated with infertility in men. However, there has been no evidence that knockout of the gene encoding PLC. abolishes the ability of sperm to induce Ca2+ oscillations in eggs. Here, we show that sperm derived from Plcz1(-/-) male mice fail to trigger Ca2+ oscillations in eggs, cause polyspermy and thus demonstrate that PLC zeta is the physiological trigger of these Ca2+ oscillations. Remarkably, some eggs fertilized by PLC zeta-null sperm can develop, albeit at greatly reduced efficiency, and after a significant time-delay. In addition, Plcz1(-/-) males are subfertile but not sterile, suggesting that in the absence of PLC zeta, spontaneous egg activation can eventually occur via an alternative route. This is the first demonstration that in vivo fertilization without the normal physiological trigger of egg activation can result in offspring. PLC zeta-null sperm now make it possible to resolve long-standing questions in fertilization biology, and to test the efficacy and safety of procedures used to treat human infertility

Reasons for prehospital delay in acute ischemic stroke

Background Prehospital delay reduces the proportion of patients with stroke treated with recanalization therapies. We aimed to identify novel and modifiable risk factors for prehospital delay. Methods and Results We included patients with an ischemic stroke confirmed by diffusion-weighted magnetic resonance imaging, symptom onset within 24 hours and hospitalized in the Stroke Center of the University Hospital Basel, Switzerland. Trained study nurses interviewed patients and proxies along a standardized questionnaire. Prehospital delay was defined as >4.5 hours between stroke onset-or time point of wake-up-and admission. Overall, 336 patients were enrolled. Prehospital delay was observed in 140 patients (42%). The first healthcare professionals to be alarmed were family doctors for 29% of patients (97/336), and a quarter of these patients had a baseline National Institute of Health Stroke Scale score of 4 or higher. The main modifiable risk factor for prehospital delay was a face-to-face visit to the family doctor (adjusted odds ratio, 4.19; 95% CI, 1.85-9.46). Despite transport by emergency medical services being associated with less prehospital delay (adjusted odds ratio, 0.41; 95% CI, 0.24-0.71), a minority of patients (39%) who first called their family doctor were transported by emergency medical services to the hospital. The second risk factor was lack of awareness of stroke symptoms (adjusted odds ratio, 4.14; 95% CI, 2.36-7.24). Conclusions Almost 1 in 3 patients with a diffusion-weighted magnetic resonance imaging-confirmed ischemic stroke first called the family doctor practice. Face-to-face visits to the family doctor quadrupled the odds of prehospital delay. Efforts to reduce prehospital delay should address family doctors and their staffs as important partners in the prehospital pathway. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02798770

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario