Discussion on how to implement a verbal scale in a forensic laboratory: benefits, pitfalls and suggestions to avoid misunderstandings

In a recently published guideline for evaluative reporting in forensic science, the European Network of Forensic Science Institutes (ENFSI) recommended the use of the likelihood ratio for the measurement of the value of forensic results. As a device to communicate the probative value of the results, the ENFSI guideline mentions the possibility to define and use a verbal scale, which should be unified within a forensic institution. This paper summarizes discussions held between scientists of our institution to develop and implement such a verbal scale. It intends to contribute to general discussions likely to be faced by any forensic institution that engages in continuous monitoring and improving of their evaluation and reporting format. We first present published arguments in favour of the use of such verbal qualifiers. We emphasize that verbal qualifiers do not replace the use of numbers to evaluate forensic findings, but are useful to communicate the probative value, since the weight of evidence in terms of likelihood ratio are still apprehended with difficulty by both the forensic scientists, especially in absence of hard data, and the recipient of information. We further present arguments that support the development of the verbal scale we propose. Recognising the limits of the use of such a verbal scale, we then discuss its disadvantages: it may lead to the spurious view according to which the value of the observations made in a given case is relative to other cases. Verbal qualifiers are also prone to misunderstandings and cannot be coherently combined with other evidence. We therefore recommend not using the verbal qualifier alone in a written statement. While scientists should only report on the probability of the findings - and not on the probability of the propositions, which are the duty of the Court - we suggest showing examples to let the recipient of information understand how the scientific evidence affects the probabilities of the propositions. To avoid misunderstandings, we also advise to mention in the statement what the results do not mean. Finally, we are of the opinion that if experts were able to coherently articulate numbers, and if recipients of information could properly handle such numbers, then verbal qualifiers could be abandoned completely. At that time, numerical expressions of probative value will be appropriately understood, as other numerical measures that most of us understand without the need of any further explanation, such as expressions for length or temperature

Earthquake statistics and fractal faults

We introduce a Self-affine Asperity Model (SAM) for the seismicity that mimics the fault friction by means of two fractional Brownian profiles (fBm) that slide one over the other. An earthquake occurs when there is an overlap of the two profiles representing the two fault faces and its energy is assumed proportional to the overlap surface. The SAM exhibits the Gutenberg-Richter law with an exponent $\beta$ related to the roughness index of the profiles. Apart from being analytically treatable, the model exhibits a non-trivial clustering in the spatio-temporal distribution of epicenters that strongly resembles the experimentally observed one. A generalized and more realistic version of the model exhibits the Omori scaling for the distribution of the aftershocks. The SAM lies in a different perspective with respect to usual models for seismicity. In this case, in fact, the critical behaviour is not Self-Organized but stems from the fractal geometry of the faults, which, on its turn, is supposed to arise as a consequence of geological processes on very long time scales with respect to the seismic dynamics. The explicit introduction of the fault geometry, as an active element of this complex phenomenology, represents the real novelty of our approach.Comment: 40 pages (Tex file plus 8 postscript figures), LaTeX, submitted to Phys. Rev.

The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis

Francisella tularensis is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unknown how F. tularensisinvades these cells. Furthermore, the consequence of inhabiting the intracellular space of red blood cells (RBCs) has not been determined. Here, we provide evidence indicating that residing within an erythrocyte enhances the ability of F. tularensis to colonize ticks following a blood meal. Erythrocyte residence protected F. tularensis from a low pH environment similar to that of gut cells of a feeding tick. Mechanistic studies revealed that the F. tularensis type VI secretion system (T6SS) was required for erythrocyte invasion as mutation of mglA (a transcriptional regulator of T6SS genes), dotU, or iglC (two genes encoding T6SS machinery) severely diminished bacterial entry into RBCs. Invasion was also inhibited upon treatment of erythrocytes with venom from the Blue-bellied black snake (Pseudechis guttatus), which aggregates spectrin in the cytoskeleton, but not inhibitors of actin polymerization and depolymerization. These data suggest that erythrocyte invasion by F. tularensis is dependent on spectrin utilization which is likely mediated by effectors delivered through the T6SS. Our results begin to elucidate the mechanism of a unique biological process facilitated by F. tularensis to invade erythrocytes, allowing for enhanced colonization of ticks

Pesticide risk assessment and management in a globally changing world—report from a European interdisciplinary workshop

[Departement_IRSTEA]Eaux [TR1_IRSTEA]BELCA [Axe_IRSTEA]DTAM-QT2-ADAPTATION [TR2_IRSTEA]ARCEAU [TR2_IRSTEA]DTAMGlobal climate change will affect worldwide agriculture in many ways. The anticipated or already occurring changes raise concerns about the sustainability of production and the ability of agriculture to feed human populations. This appeals to sustainable agriculture providing ecosystem services more efficiently than today, and accordingly to substantial evolutions of pesticide risk assessment (RA) and risk management (RM). The RA/RM issues were discussed by two European research networks in a 2011 workshop. The RA-RM-monitoring conceptual cycle tends to be virtual, with poor connections between certain steps. The design of more comprehensive emissions scenarios could improve the accuracy of predicted runoff transport, while the microcosm/mesocosm approach could help establish causal relationships between fate / exposure and populations / communities. Combined with ecological modelling, effects can be extrapolated to higher spatial and temporal scales. Risk management of diffuse sources should be designed simultaneously at the watershed and individual plot scales. Monitoring is key to assessing the effectiveness of risk reduction measures reduce and evaluate the overall quality of the aquatic compartment. More flexible monitoring strategies clearly linked to RM decisions are therefore needed. Although some technical questions remain, it is time to apply passive samplers more routinely. A set of research and development needs covering the whole RA/RM cycle is listed in conclusion

Oxygen sensing coordinates photomorphogenesis to facilitate seedling survival

Successful emergence from the soil is essential for plant establishment in natural and farmed systems. It has been assumed that the absence of light in the soil is the preeminent signal perceived during early seedling development, leading to a distinct morphogenic plan (skotomorphogenesis) [1], characterized by traits providing an adaptive advantage until emergence and photomorphogenesis. These traits include suppressed chlorophyll synthesis, promotion of hypocotyl elongation, and formation of a closed apical hook that protects the stem cell niche from damage [2, 3]. However, absence of light by itself is not a sufficient environmental signal for early seedling development [4, 5]. Reduced oxygen levels (hypoxia) can occur in water-logged soils [6-8]. We therefore hypothesized that below-ground hypoxia may be an important, but thus far undiscovered, ecological component regulating seedling development. Here, we show that survival and establishment of seedlings following darkness depend on their ability to sense hypoxia, through enhanced stability of group VII Ethylene Response Factor (ERFVII) transcription factors. Hypoxia is perceived as a positive environmental component in diverse taxa of flowering plants, promoting maintenance of skotomorphogenic traits. Hypoxia greatly enhances survival once light is perceived, while oxygen is necessary for the subsequent effective completion of photomorphogenesis. Together with light perception, oxygen sensing therefore allows an integrated response to the complex and changing physical microenvironment encountered during early seedling growth. We propose that plants monitor the soil's gaseous environment after germination, using hypoxia as a key external cue to protect the stem cell niche, thus ensuring successful rapid establishment upon emergence above ground

COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study.

BACKGROUND: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort. METHODS: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples. RESULTS: Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77). INTERPRETATION: In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables

Photoacclimation strategies in northeastern Atlantic seagrasses: Integrating responses across plant organizational levels

Seagrasses live in highly variable light environments and adjust to these variations by expressing acclimatory responses at different plant organizational levels (meadow, shoot, leaf and chloroplast level). Yet, comparative studies, to identify species' strategies, and integration of the relative importance of photoacclimatory adjustments at different levels are still missing. The variation in photoacclimatory responses at the chloroplast and leaf level were studied along individual leaves of Cymodocea nodosa, Zostera marina and Z. noltei, including measurements of variable chlorophyll fluorescence, photosynthesis, photoprotective capacities, non-photochemical quenching and D1-protein repair, and assessments of variation in leaf anatomy and chloroplast distribution. Our results show that the slower-growing C. nodosa expressed rather limited physiological and biochemical adjustments in response to light availability, while both species of faster-growing Zostera showed high variability along the leaves. In contrast, the inverse pattern was found for leaf anatomical adjustments in response to light availability, which were more pronounced in C. nodosa. This integrative plant organizational level approach shows that seagrasses differ in their photoacclimatory strategies and that these are linked to the species' life history strategies, information that will be critical for predicting the responses of seagrasses to disturbances and to accordingly develop adequate management strategies.Fundacao para a Ciencia e Tecnologia (FCT), Portugal [PTDC/MAR-EST/4257/2014

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families

Isolated complex I deficiency is the most frequently observed oxidative phosphorylation defect in children with mitochondrial disease, leading to a diverse range of clinical presentations, including Leigh syndrome. For most patients the genetic cause of the biochemical defect remains unknown due to incomplete understanding of the complex I assembly process. Nonetheless, a plethora of pathogenic mutations have been described to date in the seven mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear-encoded subunits and in six assembly factors. Whilst several mitochondrial DNA mutations are recurrent, the majority of these mutations are reported in single families. We have sequenced core structural and functional nuclear-encoded subunits of complex I in a cohort of 34 paediatric patients with isolated complex I deficiency, identifying pathogenic mutations in 6 patients. These included a novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was also identified in conjunction with a novel NDUFS2 splice site mutation (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic centre, with microsatellite and single nucleotide polymorphism analyses indicating that this was due to an ancient common founder event. Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes