Criminal rituals

Why do criminals use rituals? Past work argues that criminal rituals provide a sense of continuity or certainty in an inherently uncertain environment. We argue instead that rituals play an important organisational role. Criminal rituals facilitate internal governance and promote group activity through three mechanisms: creating common knowledge, mitigating the costs of asymmetric information, and shaping identity among group members. Using internal documents and written constitutions, we apply this framework to understand the internal governance mechanisms used by the late-nineteenth- and twentieth-century Chinese-based Green Gang.postprin

A potential library for primary MFL pedagogy: the case of Young Pathfinders

As readers of this journal will know very well, 2010 will see all KS2 (ages 7-11) pupils in England entitled to learn a modern foreign language in normal curriculum time. This development of the commitment to primary language learning should provide an excellent opportunity and experience for pupils, whilst at the same time requiring some radical changes for many teachers, schools and much of the wider language learning community. Recent research has indicated general trends suggesting an increase in primary languages already, in anticipation of this development and even beforehand. One of the most recent studies indicates that 43% of primary children currently learn a foreign language at KS2, either in class or as an extra-curricular activity, although the extent of this learning varies considerably (Driscoll, Jones and Macrory, 2004). It has also been suggested (Muijs et al, 2005) that there are certain aspects of the process that will be particularly demanding if the challenge of providing this entitlement are to be met

Prison Gangs and the Community Responsibility System

Why do prison gangs exist? Despite the prominence of formal governance mechanisms, inmates also require self-governance institutions to facilitate illicit trade. This article examines how inmates enforce agreements in the illicit contraband trade and how they resolve social disputes. We first describe how the informal prison society operates as a community responsibility system. We then present a model of prison gang organization that accounts for both environmental factors and the endogenous actions of the prison administration, encapsulated in the "warden." We find that gangs organize based on exogenous characteristics. The "warden" diffuses gang influence by maintaining the oligopolistic structure, which limits contraband but allows for orderly private allocation of prison-provided goods and dispute resolution

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

P10 Haemophagocytic lymphohistiocytosis in the returning traveller with fever... especially if slow to defervesce on treatment!

Abstract Introduction Haemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening hyperinflammatory disorder characterised by dysregulated immune activity resulting in malignant inflammation and multi-organ failure. Early recognition and treatment reduces mortality. HLH associated with rickettsial infection is described, and we present two cases of HLH secondary to severe rickettsial infection. We compare clinical and biochemical responses to IV methylprednisolone versus anakinra after HLH was suspected, identified and treated early in both presentations. We recommend a low index of suspicion for HLH for the returning traveller with fever where rickettsial infection is considered possible, especially if patients are slow to defervesce on treatment with doxycycline. Case description Case 1 was of a 63-year old-male with no past medical history of note, who presented to hospital with fevers, rigors, loose stool and jaundice one week after returning from Ethiopia. He had stayed exclusively in Addis, had not visited any rural locations and did not recall any insect bites during his trip but had contact with one dog. On review, he denied any symptoms of systemic upset prior to his presentation and had no symptoms suggestive of an underlying rheumatological disease other than myalgia and arthralgia. On examination, he had no evidence of synovitis or rash, but had hepatosplenomegaly. He was diaphoretic with daily temperature spikes of up to &amp;gt; 39 degrees Celsius. He was investigated extensively as an inpatient, but no clear infectious trigger was identified. He was treated empirically on admission with IV ceftriaxone, but continued to deteriorate and a state of hyperinflammation was suspected. By day two of his admission, his HScore was 166 and he improved rapidly after treatment with oral doxycycline and two doses of IV methylprednisolone. Case 2 was a 44-year-old male with no past medical history of note, who presented to hospital with fever, myalgia and arthralgia two weeks after returning from Cameroon. Again, he denied any rural travel and did not recall having sustained any insect bites or animal exposure. On review, he denied systemic upset prior to this presentation or other symptoms suggestive of an underlying rheumatological disease. Clinically, he had no rash, synovitis or organomegaly. He was also treated empirically with IV ceftriaxone. Two days later, initial infection screening was negative but fever persisted, and doxycycline was added. Fever persisted still, and by day four, HScore was 167. Anakinra was initiated, resulting in marked clinical improvement. Discussion Fever in the returning traveller is often associated with serious illness and the initial focus of evaluation should be trying to identify infections that are potentially life-threatening, treatable or transmissible. In both cases, this was done and patients were investigated thoroughly and extensively, but no clear infectious trigger had been identified at the time of deterioration. Treatment was therefore empirical as both people were at risk of rickettsial infection. In both cases, systemic symptoms progressed and, despite a lack of immediate identification of a causal agent, there was recognition of a hyperinflammatory response to a likely infectious trigger. Hyperinflammation and HLH have a high mortality, prompting discussion in respective HLH MDTs for initiation of immunomodulation in parallel to anti-microbial treatment. Interestingly, in case one, doxycycline was started at the same time as IV methylprednisolone, which raises the question of whether the clinical and biochemical improvement was due to the antimicrobial treatment rather than corticosteroids. However in case two, there was no immediate improvement with introduction of oral doxycycline, and it was after anakinra was introduced at least two days later that there was a dramatic clinical and biochemical response. Both cases raise the question of how much inflammation is acceptable in the context of acute inflammation when the body is trying to respond to, and tackle, an infectious agent. At what point does the inflammatory response become harmful, and is consideration and introduction of an immunomodulatory or immunosuppressive agent in the context of unidentified infection dangerous? What is the local pathway for urgent discussion of patients with hyperinflammation? These cases highlight that while the cause or trigger for HLH is unknown, the patient still needs immunomodulation promptly to prevent the potentially life-threatening manifestations of hyperinflammatory syndromes. Joint working between infectious disease and rheumatology is imperative. Key learning points • It is recognised that systemic hyperinflammation and HLH can occur in nearly any inflammatory state, but certain predisposing conditions and/or triggers warrant a high index of suspicion. These cases suggest that rickettsial infection, when considered, should prompt the clinician to have a low index of suspicion for associated HLH, and that early recognition using the HScore and treatment can lead to a good outcome. Although the exact mechanisms that trigger HLH are not fully understood, it is interesting to consider why certain infections are more likely to cause it than others. In rickettsial disease, the fourth most common infectious group of diseases associated with HLH, it is likely that the cytokine storm associated with the immune response to rickettsial infection may be involved in the pathogenesis of complicated typhus that can lead to life-threatening complications such as ARDS, DIC and HLH. It is possible that early identification of HLH in our two cases with early control of the cytokine storm with immunosuppressive and immunomodulatory treatment halted progression of further life-threatening complications associated with rickettsial disease. Although treatment in our cases with doxycycline was started early, it is interesting to think what would have happened if treatment for identified HLH was started promptly, but specific anti-rickettsial treatment delayed. Would we have allowed the host more time to mount an appropriate level of response to infection pending decision about correct and definitive treatment, or would ongoing manifestations of life-threatening complications have ensued regardless? It is also interesting to note that in both cases, only a short course of immunosuppression was required to treat HLH which is not always the case with infectious triggers of HLH. This raises the question of whether early treatment can also lead to shorter duration of disease, and highlights the role of the MDT approach to HLH. </jats:sec

Combined strategy based on pre-activated analogs of oxazaphosphorines for increased therapeutic index and immune modulation

Oxazaphosphorines (Oxaza) represented by cyclophosphamide (CPA) and ifosfamide (IFO) are still the corner stone of several polychemotherapy protocols as they are widely indicated in the treatment of numerous cancer from soft tissue sarcomas to lymphomas and immune-related diseases. However, Oxaza are prodrugs requiring cytochrome (CYP) P450 bioactivation responsible of limiting adverse effects. In the case of IFO, bioactivation leads to a low release of 4-OH-IFO (10%), which generates the active nitrogen mustard displaying DNA cross-links. Associated toxicities of IFO due to acrolein, (urotoxicity) and to chloroacetaldehyde (neuro and nephrotoxicity) have been described. Thus, increasing IFO therapeutic index could be of major interest. To circumvent these toxicities, our team has designed new pre-activated IFO analogs to avoid CYP bioactivation (Skarbek et al J Med Chem 2015). Among these analogues some have the ability to self-assemble as nanoassemblies (NAs), the others can be encapsulated within nano-lipid capsules (NLCs). These new drug delivery systems (DDS) can take advantage of passive targeting, as stealthiness of these DDS can be provided by PEGylation by using Cholesterol-polyethylene glycol or the use of surfactant. These DDS can also be functionalized by appropriate monoclonal antibodies leading to multi stage DDS with active targeting properties. Regarding CPA, it has been shown and described in literature that low doses of CPA enhance the immunity by promoting differentiation of CD4⁺ cell toward Th1. As IFO is isomeric form of CPA, it was assumed that IFO could also have such properties. Studies on immunocompetent MCA205 mouse model, an immunogenic fibrosarcoma mouse model, demonstrate a dose-dependent immunomodulation of IFO towards a modulation of the secretion of IFNy, IL-17A and IL-6 cytokines. The ongoing experiments on mouse model depleted in CD4⁺ T cells and CD8⁺ T cells show the antitumor efficacy of IFO 150mg/kg on these immune cells in tumor regression. Both strategies could lead to the design of nano-immuno-conjugates (NICs) which could benefit of the immunomodulatory effects of X-Oxaza combined to their antiproliferative properties targeted through immune checkpoint antibodies. These new functionalized DDS may provide a useful strategy to give specificity to active drugs used for many years in clinical practice. Both DDS could be grafted with mAbs which could lead to a new family of DDS aiming to combine antiproliferative and immunomodulatory properties for a dual antitumoral action Citation Format: Julia Delahousse, Charles Skarbek, Valentine Gauthier, M Desbois, Emilie Roger, C. Pioche-Durieu, M. Rivard, D. Desmaële, T. Martens, E. LeCam, Jean-Pierre Benoit, P. Couvreur, Nathalie Chaput-Gras, Angelo Paci. Combined strategy based on pre-activated analogs of oxazaphosphorines for increased therapeutic index and immune modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2195. doi:10.1158/1538-7445.AM2017-219

Analysis of density based and fuzzy c-means clustering methods on lesion border extraction in dermoscopy images

<p>Abstract</p> <p>Background</p> <p>Computer-aided segmentation and border detection in dermoscopic images is one of the core components of diagnostic procedures and therapeutic interventions for skin cancer. Automated assessment tools for dermoscopy images have become an important research field mainly because of inter- and intra-observer variations in human interpretation. In this study, we compare two approaches for automatic border detection in dermoscopy images: density based clustering (DBSCAN) and Fuzzy C-Means (FCM) clustering algorithms. In the first approach, if there exists enough density –greater than certain number of points- around a point, then either a new cluster is formed around the point or an existing cluster grows by including the point and its neighbors. In the second approach FCM clustering is used. This approach has the ability to assign one data point into more than one cluster.</p> <p>Results</p> <p>Each approach is examined on a set of 100 dermoscopy images whose manually drawn borders by a dermatologist are used as the ground truth. Error rates; false positives and false negatives along with true positives and true negatives are quantified by comparing results with manually determined borders from a dermatologist. The assessments obtained from both methods are quantitatively analyzed over three accuracy measures: border error, precision, and recall. </p> <p>Conclusion</p> <p>As well as low border error, high precision and recall, visual outcome showed that the DBSCAN effectively delineated targeted lesion, and has bright future; however, the FCM had poor performance especially in border error metric.</p

The burden of breast, cervical, and colon and rectum cancer in the Balkan countries, 1990–2019 and forecast to 2030.

Background Despite effective prevention and control strategies, in countries of the Balkan region, cancers are the second leading cause of mortality, closely following circulatory system diseases. Objective To describe trends in the burden of breast, cervical, and colon and rectum cancer in the Balkan region and per country between 1990 and 2019, including a forecast to 2030. Methods We described the 2019 Global Burden of Disease (GBD) estimates for breast, cervical, and colon and rectum cancers in eleven Balkan countries over the period 1990–2019, including incidence, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALYs) rates per 100,000 population and accompanied 95% uncertainty interval. With the Autoregressive Integrated Moving Average, we forecasted these rates per country up to 2030. Results In the Balkan region, the highest incidence and DALYs rates in the study period were for colon and rectum, and breast cancers. Over the study period, the DALYs rates for breast cancer per 100,000 population were the highest in Serbia (reaching 670.84 in 2019) but the lowest in Albania (reaching 271.24 in 2019). In 2019, the highest incidence of breast cancer (85 /100,000) and highest YLD rate (64 /100,000) were observed in Greece. Romania had the highest incidence rates, YLD rates, DALY rates, and YLL rates of cervical cancer, with respective 20.59%, 23.39% 4.00%, and 3.47% increases for the 1990/2019 period, and the highest forecasted burden for cervical cancer in 2030. The highest incidence rates, YLD rates and DALY rates of colon and rectum cancers were continuously recorded in Croatia (an increase of 130.75%, 48.23%, and 63.28%, respectively), while the highest YLL rates were in Bulgaria (an increase of 63.85%). The YLL rates due to colon and rectum cancers are forecasted to progress by 2030 in all Balkan countries. Conclusion As most of the DALYs burden for breast, cervical, and colon and rectum cancer is due to premature mortality, the numerous country-specific barriers to cancer early detection and quality and care continuum should be a public priority of multi-stakeholder collaboration in the Balkan region