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This introduction to the book begins with a narrative of the prevalence of gun violence in the United States and the trafficking of gun violence into Mexico and Latin America. It canvasses the current statistics of gun-related murders, suicides, mass shootings, and school shootings compiled by the CDC, the Pew Research Institute, Bureau of Alcohol, Tobacco, Firearms and Explosives, the Giffords Center, and other agencies collecting gun violence data. The introduction sets forth the themes of the book, including locating the landscape of firearms litigation in the history of mass tort litigation, the ineffectiveness of various gun regulatory initiatives, the historical immunity of the firearms industry from liability for gun harms, and the recent inroads on the ability to sue firearms defendants through the enactment of targeted consumer protection and public nuisance firearms accountability statutes. The introduction suggests the argument that the 1998 Tobacco Master Settlement Agreement demonstrated that impervious, dangerous product industries could finally be held accountable, and that the Sandy Hook Elementary School litigation marked a pivotal point in opening a pathway toward suing the firearms industry and holding it accountable for gun harms.
Immune dysregulation contributes to the pathophysiology of depression and is a potential link between depression and comorbid medical conditions. DNA methylation is a dynamic transcriptional regulator of the immune system.
Aims
To study changes in DNA methylation of disease- and comorbidity-associated immune genes in patients with and without depression diagnoses from the German BiDirect Study.
Method
We performed a cross-sectional (baseline, y0) and longitudinal (consecutive assessments at 3-year intervals, y0, y3, y6) differential methylation analyses of 382 immune-related genes associated with depression, obesity, diabetes and/or gout in 276 patients with depression and in 207 individuals without a lifetime depression diagnosis from the BiDirect Study. In addition, we applied unsupervised clustering to identify subgroups of individuals with depression based on longitudinal methylation patterns.
Results
There were no significant methylation changes between individuals with depression and controls at baseline. Follow-up analyses used to assess the top (P < 0.05) 151 methylation probes longitudinally identified 42 CpG sites that showed time-dependent changes associated with depression, and defined 3 depression clusters with differential profiles of serum inflammation markers at baseline. The implicated genes corresponded in the majority to those associated with diabetes risk, and were enriched in processes relevant for haematopoiesis.
Conclusions
Our results suggest that immune dysregulation associated with DNA methylation profiles contributes to the pathophysiology of depression and is a plausible link to chronic medical conditions such as diabetes.
Cydalima perspectalis (Walker, 1859) (Lepidoptera: Crambidae) larvae feed on Buxus. It is considered to be the most critical pest of boxwood trees. This study investigated whether different strains of Trichoderma harzianum had an effect on the biocontrol of larvae feeding on boxwood leaves whose nitrogen content was varied by fertilisation. Larvae were collected while feeding on boxwood seedlings in Rize parks and gardens in June 2021. In addition, G1 (no fertilisation), G2 (1.55%), and G5 (1.67%) leaves with different nitrogen concentrations obtained by nitrogen fertilisation were also used as food. As biocontrol agents, ID11D and YP1A strains of T. harzianum were applied in three doses: 50, 100, and 200 μL per water. In total, 21 different groups were created. The nutritional indices of the larvae belonging to the different groups were calculated. In addition, the activities of phenoloxidase, superoxide dismutase, catalase, and glutathione peroxidase activities were measured by taking haemolymph samples. In both strains, the enzyme activities increased with the dose applied. However, it was found that the enzyme activities of the ID11D strain applied were higher than those of the YP1A strain. It can be said that the ID11D strain is effective in controlling C. perspectalis larvae feeding on fertilised boxwood and the YP1A strain is effective in controlling larvae feeding on unfertilised boxwood.
The Old Regime period in which war proved the norm and peace the exception witnessed the development of the modern law of nations. Questions of international law assumed a new urgency as did the status of diplomatic agents. By this time the existence of permanent embassies could still be deplored but no longer questioned, and diplomatic immunity could not be disputed, reinforced as it was by a body of precedent and tradition. This period witnessed first the expansion and later the contraction of diplomatic privilege. European aristocratic society reinforced diplomatic privilege, for the status of the ambassador was inextricably intertwined with that of the ruler. The explosive expansion of diplomats and their staff led many theorists, such as Grotius and Vattel, to analyse the evolving conventions, such as the importance of the civil immunity of the ambassador and the liability of the embassy staff. Practice tended to reinforce privileges identified as personal, that is, attached to the ambassador himself. Of these the exemption from criminal liability was perhaps the most important. Among territorially defined privileges, the right of asylum and the notorious right of quarter were first expanded and later either limited or eliminated.
This chapter charts the profound transformations undergone by diplomacy, both secular and papal, in an age of dramatic intellectual, political and military upheaval. Considering both scholarship and practice, the chapter assesses the rise of ‘resident diplomacy’ and highlights the new structures that were put in place in order to manage longer missions. The investigation of the right to send ambassadors reveals persistent traits of pluralism in early modern Europe, while the plurality of diplomatic envoys and roles is taken into account to make the complexity of the notion of diplomatic status more apparent: this status, in fact, cannot be reduced to that of a fully fledged ambassador exclusively committed to the object of their official mission. Information-gathering, negotiation and mediation are singled out as the most significant diplomatic functions. Changes in the conception of diplomatic inviolability and immunity are also considered, and include the emergence of the idea of extraterritoriality concerning both the person of the ambassador and diplomatic premises.
Varicella zoster virus is a highly infectious virus that causes a vesicular rash and associated malaise, fever, and headaches. While the majority of the population has either had previous infection in childhood or vaccination, seronegative individuals are at risk of primary infection. Primary infection in pregnancy poses a risk of fetal transmission and congenital varicella syndrome, as well as risk of severe morbidity to the mother. Congenital varicella syndrome includes a conglomeration of anomalies such as cutaneous scarring, limb hypoplasia, microcephaly, and chorioretinitis. Seronegative mothers exposed to varicella should be treated with varicella immune globulin to reduce the risk of a primary varicella infection. If a pregnant woman develops varicella, oral acyclovir should be started to reduce the severity of infectious complications and the number of lesions. All women of reproductive age should be asked about their varicella status prior to conceiving. Varicella-naïve women should ideally complete the two-dose VARIVAX vaccine at least 4 weeks prior to conceiving.
International criminal law recognizes certain defences, excuses and justifications that may be raised against a charge of genocide. These include mistake of fact, duress and necessity and self-defence. The defences are codified in detailed provisions of the Rome Statute but they are also derived from case law. The Rome Statute declares that an order to commit genocide is ’manifestly unlawful’ and therefore unavaible to an accused person. A defence of ’official capacity’ is explicitly excluded by article IV of the Convention whereby offenders must be punished ’whether they are constitutionally responsible rulers, public officials or private individuals’.
This article analyses the depictions of immunity and immunological functions employed in proprietary medical advertising in British newspapers between 1890 and 1940. Using marketing copy to gain insights into the ways immunity was presented to the public and normalised outside of medical institutions and publications, I offer four main areas of discussion. First, I present an analysis of the ways advertisements evoked both natural and artificial immunity in their marketing copy, thereby affording us insights into the ways immunity was made palatable both to those supportive of and opposed to vaccinations. I then unpack the ways in which this advertising copy often emphasised immunity rather than the immunological, that is, presented immunity as resistance to infection achieved by purchasing particular brands, rather than as part of a defensive process taking place at a cellular level. Third, I examine the ways in which advertisements engaged with futurity and drew on a narrative of social exclusion that pitted created communities of the immune against the non-immune. Finally, I analyse the ways in which immunity was used to connect the biological and the psychological, looking particularly at the ways immunity against worry was sold to the public.
We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status among six ethnic groups in Amsterdam, the Netherlands. We analysed participants of the Healthy Life in an Urban Setting cohort who were tested for SARS-CoV-2 spike protein antibodies between 17 May and 21 November 2022. We categorized participants with antibodies as only infected, only vaccinated (≥1 dose), or both infected and vaccinated, based on self-reported prior infection and vaccination status and previous seroprevalence data. We compared infection and vaccination status between ethnic groups using multivariable, multinomial logistic regression. Of the 1,482 included participants, 98.5% had SARS-CoV-2 antibodies (P between ethnic groups = 0.899). Being previously infected and vaccinated ranged from 36.2% (95% confidence interval (CI) = 28.3–44.1%) in the African Surinamese to 64.5% (95% CI = 52.9–76.1%) in the Ghanaian group. Compared to participants of Dutch origin, participants of South-Asian Surinamese (adjusted odds ratio (aOR) = 6.74, 95% CI = 2.61–17.45)), African Surinamese (aOR = 23.32, 95% CI = 10.55–51.54), Turkish (aOR = 8.50, 95% CI = 3.05–23.68), or Moroccan (aOR = 22.33, 95% CI = 9.48–52.60) origin were more likely to be only infected than infected and vaccinated, after adjusting for age, sex, household size, trust in the government’s response to the pandemic, and month of study visit. SARS-CoV-2 infection and vaccination status varied across ethnic groups, particularly regarding non-vaccination. As hybrid immunity is most protective against coronavirus disease 2019, future vaccination campaigns should encourage vaccination uptake in specific demographic groups with only infection.
Edited by
Ottavio Quirico, University of New England, University for Foreigners of Perugia and Australian National University, Canberra,Walter Baber, California State University, Long Beach
The role of judges in implementing climate policies has become a crucial component of the existing governance framework regulating climate change action. Litigation focusing on more ambitious climate action is trending globally. Individuals, local authorities and NGOs are bringing lawsuits against national governments, holding them accountable to their legal obligations and engendering policy change. Due to the constitutional doctrine of the separation of powers, the justiciability of climate policy is questioned. Disagreements exist between advocates of an activist judicial role and those in favour of legislative and executive discretion. The main question is to what extent the judiciary can oblige other government branches to take urgent preventative action, particularly to implement or adjust climate policies. Their role in implementing climate policies is analysed from a comparative perspective, considering theoretical debates on the doctrine of the separation of powers in different legal systems and relevant case-law. The chapter connects international and domestic issues and highlights recommendations to foster effective implementation of more ambitious climate policies.
Glycosylation modifications of proteins and glycan hydrolysis are critical for protein function in biological processes. Aberrations in glycosylation enzymes are linked to lysosomal storage disorders (LSDs), immune interactions, congenital disorders and tumour progression. Mannosidase alpha class 2B member 1 (MAN2B1) is a lysosomal hydrolase from the α-mannosidase family. Dysfunction of MAN2B1 has been implicated as causative factors in mannosidosis, a lysosomal storage disorder characterised by cognitive impairment, hearing loss and immune system and skeletal anomalies. Despite decades of research, its role in pathogenic infections, autoimmune conditions, cancers and neurodegenerative pathologies is highly ambiguous. Future studies are required to shed more light on the intricate functioning of MAN2B1. To this end, we review the biological functions, expression patterns, enzymatic roles and potential implications of MAN2B1 across various cell types and disease contexts. Additionally, the novel insights presented in this review may aid in understanding the role of MAN2B1 in immune cells, thereby paving the way for targeted therapeutic interventions in immune-related disorders.
This chapter presents how scientists currently use the increasing number of individuals who live to an age above 90 years (i.e. long-lived individuals) to investigate biological determinants of longevity. It will provide an overview of the most extensive studies of exceptionally long-lived individuals and long-living families that have been established since the early 1970s. The focus of the chapter will be on the metabolic phenotypes and the genetic determinants that characterize them. It will discuss the delayed occurrence of age-related disease in long-lived individuals and their offspring as well as their favourable immune-metabolic profile, that is, improved glycaemic control, lipid and thyroid metabolism and immunity. Moreover, it will provide an overview of studies focused on unravelling the genetic component of longevity, which is assumed to be partly responsible for the observed immune-metabolic profile. The findings from these studies indicate that longevity is most likely determined by many different rare protective genetic variants that still need to be identified, for example using whole genome/exome sequencing approaches. Last, but not least, the chapter will discuss some of the implications of the presented findings for medical research on ageing and age-related diseases.
Osteoarthritis (OA), a disease with a multifactorial aetiology and an enigmatic root cause, affects the quality of life of many elderly patients. Even though there are certain medications utilised to reduce the symptomatic effects, a reliable treatment method to reverse the disease is yet to be discovered. Zinc is a cofactor of over 3000 proteins and is the only metal found in all six classes of enzymes. We explored zinc’s effect on the immune system and the bones as OA affects both. We also discussed zinc-dependent enzymes, highlighting their significant role in the disease’s pathogenesis. It is important to note that both excessive and deficient zinc levels can negatively affect bone health and immune function, thereby exacerbating OA. The purpose of this review is to offer a better understanding of zinc’s impact on OA pathogenesis and to provide clarity regarding its beneficial and detrimental outcomes. We searched thoroughly systematic reviews, meta-analysis, review articles, research articles and randomised controlled trials to ensure a comprehensive review. In brief, using zinc supplementation in the treatment of OA may act as a doubled-edged sword, offering potential benefits but also posing risks.
This chapter discusses the immunities of individuals in relation to criminal prosecution for international crimes. It introduces the main two types of immunity: functional immunity and personal immunity. It discusses diplomatic immunity as a particular illustration. The chapter then discusses limits on functional immunity, with the Pinochet decision and other precedents. It then discusses the harder situation of personal immunity, as explained by the International Court of Justice in the Arrest Warrant Decision. It reviews various ways that states have relinquished immunity, including through Security Council resolutions under Chapter VII of the UN Charter, or through ratification of the ICC Statute. The chapter surveys the many issues about whether Security Council referrals to the ICC, coupled with a duty to cooperate fully, have the same effect of removing immunity. The chapter then discusses the legal position advanced by the Sierra Leone Special Court in the Taylor case, and endorsed by the ICC Appeals Chamber in the Al Bashir case, that there are no immunities before international courts, by virtue of their special nature. The chapter canvasses criticism of the theory as well arguments in favour of it.
The ICC launched in 2002 to judge cases against individuals accused of war crimes, crimes against humanity, and genocide. It is unique among international institutions in this book in that it imposes its obligations upon individual persons rather than governments. This chapter shows the powers and limits on the authority of the ICC to punish people for large-scale atrocities. The practical power of the ICC is shaped by both the difficulty of apprehending people and the active work of those who wish to remain insulated from accountability.
This chapter provides a basic introduction to virology, dealing with the history of viruses, taxonomy, virus replication stages (attachment, entry, uncoating, transcription, translation, assembly and release). It also deals with the immune response to viruses, including innate immune response, adaptive immunity, cell-mediated response, antibody-mediated response, viral pathogenesis, viral tropisms, viral spread, viral persistence, viral virulence and host factors.
We aimed to investigate the intricate interplay between genetic predisposition and lifestyle factors on stroke. We conducted a comprehensive genome-wide association study to identify the genetic variants linked to stroke in the participants who experienced a stroke event (cases; n 672) and those with no stroke history (non-stroke; n 58 029) in a large hospital-based cohort. Using generalised multifactor dimensionality reduction, we identified genetic variants with interactive effects and constructed polygenic risk scores (PRS) by summing up the risk alleles from the genetic variants. Food intake was measured with a validated semi-quantitative FFQ. No significant differences in stroke incidence were seen in demographic variables between the two groups. Among the metabolic indicators, only serum TAG levels were higher in males with stroke than those without stroke. The daily nutrient intake, dietary inflammation index, glycaemic index, dietary patterns, alcohol consumption, exercise and smoking did not display associations with the OR for stroke. The stroke-linked genetic variants were related to the IL-18 pathway. After accounting for covariates, the PRS derived from the 5-, 6- and 7-SNP models were positively associated with stroke chance with 2·5-, 2·9- and 2·8-fold. Furthermore, interactions between genetic predisposition and dietary components, including energy, carbohydrates, n-3 fatty acids and branched-chain amino acids (BCAA), that affected OR for stroke were observed. A high intake of energy, carbohydrates and BCAA and a low intake of n-3 fatty acids were positively associated with the chances of stroke occurrence. In conclusion, understanding the interaction between genetic variants and lifestyle factors can assist in developing stroke prevention and management strategies.
This chapter examines section 117 of the Australian Constitution, which prohibits States from discriminating against residents in other States. Section 117 is a peculiar provision. It is not a limitation on power that invalidates offending laws: it confers an immunity on some individuals (namely, those who are Australians resident in a State, but not those who are non-Australians resident in a State or anyone resident in a territory or overseas) from offending laws. The basic methodology for determining whether section 117 applies involves a comparison of the position of the plaintiff in two scenarios. The first scenario is the actual situation of a plaintiff. The second scenario is the hypothetical situation of the plaintiff being a resident in the State alleged to have discriminated against the plaintiff. If the treatment of the plaintiff in both scenarios by the State would be the same, then there is no discrimination and section 117 does not apply. If the treatment of the plaintiff in both scenarios would be different, then there is discrimination on the ground of State residency and section 117 renders the plaintiff immune from the offending law.
This review will provide an overview of the immune system and then describe the effects of frailty, obesity, specific micronutrients and the gut microbiota on immunity and susceptibility to infection including data from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic where relevant. A key role for the immune system is providing host defence against pathogens. Impaired immunity predisposes to infections and to more severe infections and weakens the response to vaccination. A range of nutrients, including many micronutrients, play important roles in supporting the immune system to function. The immune system can decline in later life and this is exaggerated by frailty. The immune system is also weakened with obesity, generalised undernutrition and micronutrient deficiencies, which all result in increased susceptibility to infection. Findings obtained during the SARS-CoV-2 pandemic support what was already known about the effects of ageing, frailty and obesity on immunity and susceptibility to infection. Observational studies conducted during the pandemic also support previous findings that multiple micronutrients including vitamins C, D and E, zinc and selenium and long-chain n-3 fatty acids are important for immune health, but whether these nutrients can be used to treat those already with coronavirus disease discovered in 2019 (COVID-19), particularly if already hospitalised, is uncertain from current inconsistent or scant evidence. There is gut dysbiosis in patients with COVID-19 and studies with probiotics report clinical improvements in such patients. There is an inverse association between adherence to a healthy diet and risk of SARS-CoV-2 infection and hospitalisation with COVID-19 which is consistent with the effects of individual nutrients and other dietary components. Addressing frailty, obesity and micronutrient insufficiency will be important to reduce the burden of future pandemics and nutritional considerations need to be a central part of the approach to preventing infections, optimising vaccine responses and promoting recovery from infection.
The effects of monolaurin (ML) on the health of piglets infected with porcine epidemic diarrhoea virus (PEDV) have not been fully understood. This study aimed to investigate its role in blood biochemical profile, intestinal barrier function, antioxidant function and the expression of antiviral genes in piglets infected with PEDV. Thirty-two piglets were randomly divided into four groups: control group, ML group, PEDV group and ML + PEDV group. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 d before PEDV infection. Results showed that PEDV infection significantly decreased D-xylose content and increased intestinal fatty acid-binding protein content, indicating that PEDV infection destroyed intestinal barrier and absorption function. While it could be repaired by ML administration. Moreover, ML administration significantly decreased plasma blood urea nitrogen and total protein content upon PEDV infection. These results suggested ML may increase protein utilisation efficiency. ML administration significantly decreased the number of large unstained cells and Hb and increased the number of leucocytes and eosinophils in the blood of PEDV-infected piglets, indicating ML could improve the immune defense function of the body. In the presence of PEDV infection, ML administration significantly increased superoxide dismutase and catalase activities in blood and colon, respectively, indicating ML could improve antioxidant capacity. Besides, ML administration reversed the expression of ISG15, IFIT3 and IL-29 throughout the small intestine and Mx1 in jejunum and ileum, indicating the body was in recovery from PEDV infection. This study suggests that ML could be used as a kind of feed additive to promote swine health upon PEDV infection.