The Right to Self-Defence in National and International Law: The Role of the Imminence Requirement

This article explores the doctrine of self-defence within the context of the challenges directed at the imminence requirement, from the perspective of both national and international law. The article will attempt to illustrate that the requirement of imminence underlines the political character of the self-defence doctrine wherein private force may only be resorted to in the absence of institutional protection. This study will argue that the imminence rule can not merely be regarded as a "proxy" for establishing necessity; rather, the elements of imminence, necessity, and proportionality are inextricably connected to ensure that defensive force is only resorted to when national or international authorities are not in a position to prevent an illegal aggression, and that the defensive lethal force is not abused.

The Contours of the Right to Self-defence: Is the Requirement of Imminence Merely a Translator for the Concept of Necessity?

The right to self-defence has lately been subjected to intense academic controversy, both at the domestic and international level. The debate is focused on the question of whether or not the requirement of imminence is merely a translator for the notion of necessity. At the domestic level, the debate has mainly been kindled by feminist scholars, who, in the context of the 'battered woman', argue that the requirement of imminence should be discarded from the contours of the self-defence doctrine. The purpose of this article is to prove the necessity of the imminence requirement as a litmus test to detect possible abuses of the self-defence doctrine.

Chloroquine causes lysosomal dysfunction in neural retina and RPE: Implications for retinopathy

Chronic use of chloroquine has been shown to induce numerous pathophysiological defects in the retina. This drug has the ability to alter pH of intracellular compartments and lysosomal function of the retinal pigment epithelium (RPE) and retinal neurons may constitute the basis of chloroquine retinopathy. The aim of the current study was to investigate pathogenic alterations in retinal cells continuously exposed to chloroquine using appropriate in vivo and in vitro models.

C5a-mediated neutrophil phagocytic dysfunction is RhoA-dependent and predicts nosocomial infection in critically ill patients.

Critically ill patients are at heightened risk for nosocomial infections. The anaphylatoxin C5a impairs phagocytosis by neutrophils. However, the mechanisms by which this occurs and the relevance for acquisition of nosocomial infection remain undetermined. We aimed to characterize mechanisms by which C5a inhibits phagocytosis in vitro and in critically ill patients, and to define the relationship between C5a-mediated dysfunction and acquisition of nosocomial infection. In healthy human neutrophils, C5a significantly inhibited RhoA activation, preventing actin polymerization and phagocytosis. RhoA inhibition was mediated by PI3Kd. The effects on RhoA, actin, and phagocytosis were fully reversed by GM-CSF. Parallel observations were made in neutrophils from critically ill patients, that is, impaired phagocytosis was associated with inhibition of RhoA and actin polymerization, and reversed by GM-CSF. Among a cohort of 60 critically ill patients, C5a-mediated neutrophil dysfunction (as determined by reduced CD88 expression) was a strong predictor for subsequent acquisition of nosocomial infection (relative risk, 5.8; 95% confidence interval, 1.5-22; P = .0007), and remained independent of time effects as assessed by survival analysis (hazard ratio, 5.0; 95% confidence interval, 1.3-8.3; P = .01). In conclusion, this study provides new insight into the mechanisms underlying immunocompromise in critical illness and suggests novel avenues for therapy and prevention of nosocomial infection.

Nasal potential difference to detect Na+ channel dysfunction in acute lung injury

Pulmonary fluid clearance is regulated by the active transport of Na+ and Cl- through respiratory epithelial ion channels. Ion channel dysfunction contributes to the pathogenesis of various pulmonary fluid disorders including high-altitude pulmonary edema (HAPE) and neonatal respiratory distress syndrome (RDS). Nasal potential difference (NPD) measurement allows an in vivo investigation of the functionality of these channels. This technique has been used for the diagnosis of cystic fibrosis, the archetypal respiratory ion channel disorder, for over a quarter of a century. NPD measurements in HAPE and RDS suggest constitutive and acquired dysfunction of respiratory epithelial Na+ channels. Acute lung injury (ALI) is characterized by pulmonary edema due to alveolar epithelial-interstitial-endothelial injury. NPD measurement may enable identification of critically ill ALI patients with a susceptible phenotype of dysfunctional respiratory Na+ channels and allow targeted therapy toward Na+ channel function. text of link

Müller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products.

Aims/hypothesis: The impact of AGEs and advanced lipoxidation end-products (ALEs) on neuronal and Müller glial dysfunction in the diabetic retina is not well understood. We therefore sought to identify dysfunction of the retinal Müller glia during diabetes and to determine whether inhibition of AGEs/ALEs can prevent it.

Methods: Sprague-Dawley rats were divided into three groups: (1) non-diabetic; (2) untreated streptozotocin-induced diabetic; and (3) diabetic treated with the AGE/ALE inhibitor pyridoxamine for the duration of diabetes. Rats were killed and their retinas were evaluated for neuroglial pathology. Results: AGEs and ALEs accumulated at higher levels in diabetic retinas than in controls (p<0.001). AGE/ALE immunoreactivity was significantly diminished by pyridoxamine treatment of diabetic rats. Diabetes was also associated with the up-regulation of the oxidative stress marker haemoxygenase-1 and the induction of glial fibrillary acidic protein production in Müller glia (p<0.001). Pyridoxamine treatment of diabetic rats had a significant beneficial effect on both variables (p<0.001). Diabetes also significantly altered the normal localisation of the potassium inwardly rectifying channel Kir4.1 and the water channel aquaporin 4 to the Müller glia end-feet interacting with retinal capillaries. These abnormalities were prevented by pyridoxamine treatment.

Conclusions/interpretation: While it is established that AGE/ALE formation in the retina during diabetes is linked to microvascular dysfunction, this study suggests that these pathogenic adducts also play a role in Müller glial dysfunction.

Oromotor dysfunction and communication impairments in children with cerebral palsy: a Register study

Aim  To report the prevalence, clinical associations, and trends over time of oromotor dysfunction and communication impairments in children with cerebral palsy (CP).

Method  Multiple sources of ascertainment were used and children followed up with a standardized assessment including motor speech problems, swallowing/chewing difficulties, excessive drooling, and communication impairments at age 5 years.

Results  A total of 1357 children born between 1980 and 2001 were studied (781 males, 576 females; median age 5y 11mo, interquartile range 3–9y; unilateral spastic CP, n=447; bilateral spastic CP, n=496; other, n=112; Gross Motor Function Classification System [GMFCS] level: I, 181; II, 563; III, 123; IV, 82; IV, 276). Of those with ‘early-onset’ CP (n=1268), 36% had motor speech problems, 21% had swallowing/chewing difficulties, 22% had excessive drooling, and 42% had communication impairments (excluding articulation defects). All impairments were significantly related to poorer gross motor function and intellectual impairment. In addition, motor speech problems were related to clinical subtype; swallowing/chewing problems and communication impairments to early mortality; and communication impairments to the presence of seizures. Of those with CP in GMFCS levels IV to V, a significant proportion showed a decline in the rate of motor speech impairment (p=0.008) and excessive drooling (p=0.009) over time.

Interpretation  These impairments are common in children with CP and are associated with poorer gross motor function and intellectual impairment.