Provocative Challenge Research Articles

Protocol for a systematic review and meta-analysis of interventions aimed at delabeling low-risk penicillin allergies with consideration for sex and gender

BackgroundApproximately, 10% of people report a penicillin allergy; however, more than 90% can safely undergo delabeling after a detailed history, oral challenge, or other investigations such as penicillin skin testing (PST). Although PST is the gold standard, the results can be heterogeneous, and awaiting specialist assessment may take an inordinate amount of time. Therefore, oral provocation challenge has become acceptable for individuals with low-risk penicillin allergy histories. There also appears to be an association with increased prevalence of adverse drug reaction reporting in female individuals, which may translate to penicillin allergy prevalence; however, the evidence has not been assessed through a sex and gender lens. This systematic review will identify and synthesize the findings from studies that report measures of effectiveness and safety of interventions aimed at delabeling penicillin allergies in low-risk individuals. Information related to sex and gender will be extracted, where available, to understand potential differences in allergy reporting and patient outcomes.MethodsThe Cochrane Handbook for Systematic Reviews of Interventions and the Centre for Review and Dissemination’s Guidance for Undertaking Reviews in Health Care will be used as frameworks for conducting this systematic review. The literature search will be conducted by a medical librarian (B. M. M.) and will consist of a search strategy to identify and retrieve published studies that meet our inclusion criteria. Studies that require penicillin skin testing (PST) as a step prior to other interventions will be excluded. Integrated knowledge translation involving co-design was carried out for this systematic review protocol creation. Data extraction will be conducted at four levels: (1) study level, (2) patient level, (3) intervention level, and (4) outcome level. A narrative descriptive synthesis of results and risk of bias of all included studies will be provided, and, if relevant, a meta-analysis will be performed.DiscussionThe dissemination of findings from this knowledge synthesis to various stakeholders is intended to inform on options for evidence-based interventions to aid in delabeling penicillin allergies in individuals with a low risk of experiencing a hypersensitivity reaction. Detailed reporting on the characteristics of delabeling interventions as well as the effectiveness of similar interventions will benefit policy makers considering the implementation of a penicillin allergy delabeling protocol. Additionally, findings from this systematic review will report on the current evidence regarding the role of sex and gender in both the prevalence and outcomes associated with the presence of penicillin allergies.Systematic review registrationPROSPERO CRD42022336457.

„Býti národním v umění je směšný pleonasmus. Národní je i spánek.“ K německočeské debatě nad moderním meziválečným uměním

As an art historian who has long focused on the manifestations of the visual culture of the German-speaking scene in the Czech lands, I have repeatedly encountered the topic of perceiving the “Czechness” and “worldliness” of domestic production. From my research perspective, I see two levels in this beautiful and provocative challenge. The first is the evergreen of German-Bohemian art, i.e. if we apply a national or geographical scale to the artistic expressions that emerged from the Czech lands. Today, of course, we take a geographical view, but if we look at the production of individual regions side by side, it is impossible not to see clear differences on the part of the ethnically Czech and German scenes. Capturing and defining more universally some of the subliminal specifics that are apparent at first glance is a challenge that still occupies me mentally, despite the awareness of the absurdity of searching for a national definition of art. Fixing the key features is complicated by the existence of multicultural exceptions, which often introduce an element of Judaism into the traditional dualism of the period under review. These exceptions successfully disrupt the flattened idea of parallel Czech- and German-speaking cultural and social worlds of the Czech lands. Moreover, it is precisely these exceptions that are often the bearers of tendencies towards imaginary worldliness, which brings us to the second level of this consideration – to what extent and through what phenomena the territorially and numerically relatively small art scene of the Czech lands can be perceived as world-class. The answer may be the market, or a confident search for regional authenticity. In the words of Josef Kroutvor, “minor branches of modernity.” It seems to me that in today’s global world, their offsprings are more important than many textbook examples of the avant-garde.

Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus

BackgroundPenicillin-associated exanthems in the setting of infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) are often viewed as a transient event, and not a true allergy. Recent evidence challenges this and suggest a notable subset of patients retain penicillin hypersensitivity. ObjectiveWe investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with a penicillin-associated rash occurring in the setting of EBV infection. MethodRetrospective analysis of patients referred for penicillin allergy testing to an Australian tertiary hospital captured from 2015 to 2023 was carried out. ResultsOf 2,066 patients, 23 (1%) had a penicillin-associated rash during an historic EBV infection; 16 (70%) female, median 18 years (interquartile range [IQR] 16-20) at index reaction, median 38 years (IQR 33.5-57) when allergy tested. Skin-prick and delayed-intradermal testing (D-IDT) to a penicillin panel were performed and oral provocation challenge in those testing negative. Persistent sensitisation was shown in 6/23 (26%); 4/6 (67%) positive D-IDT, 3/6 (50%) positive oral challenge. Notably, 5/6 (83%) had a severe maculopapular exanthem (sMPE) with facial swelling, including 2/6 (33%) with probable drug reaction with eosinophilia and systemic symptoms (DRESS) during the index reaction, compared with 0/17 (0%) in patients tolerating penicillin on re-exposure. ConclusionThis study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated sMPE in the setting of EBV, even if occurring during childhood or adolescence.

Comparing Skin and Serum Testing to Direct Challenge Outcomes in Children With β-Lactam Allergies

BackgroundThere is a scarcity of prospective studies investigating the relative roles of skin prick and intradermal testing, serum-specific Immunoglobulin E, and extended oral challenges in diagnosing children with reported beta-lactam allergies. ObjectiveTo determine the sensitivity and specificity of skin testing and serum-specific Immunoglobulin E in children with beta-lactam allergies, with immediate and non-immediate historic reactions. MethodsFour hundred children with parent-reported beta-lactam allergies were recruited into an open-label prospective study. Detailed allergy histories were collected. Those with medically observed and documented histories of anaphylaxis, requiring epinephrine, or SCARs were excluded. In total, 380 children underwent all testing modalities and a direct provocation test. Each child was followed up for a minimum of three years. ResultsTrue allergy in children was uncommon, 8·3% reacted to the direct provocation challenge or the 5-day extended oral provocation challenge. Children reporting cephalosporin allergy or a reaction within one year were more likely to react to direct provocation testing. The sensitivity, specificity, and positive predictive value of skin testing was 12·5%, 98·8% and 20·0% for direct challenge outcomes, 4·76%, 99·0% and 25·0% for extended challenge outcomes, and 6·9%, 99·0% and 40·0% for both challenges combined. Follow-up investigations revealed that 5·7% of children had a mild repeat reaction and 2·7% continued to avoid the culprit despite successful delabeling. The relabeling rate for children readmitted to hospital was 15% with the relabeing being unfounded. ConclusionGenuine beta-lactam allergies were rare, with over 90% of children effectively delabeled. Skin and serum-specific Immunoglobulin E testing did not aid the diagnosis of beta-lactam antibiotic allergy in children, regardless of medical history. Extended oral challenges proved valuable in confirming allergies and boosted parental confidence.

Conducting a successful diet trial for the diagnosis of food allergy in dogs and cats.

A limited antigen diet trial and subsequent food provocation is currently the optimal method of confirming a diagnosis of food allergy in dogs and cats. However, performing an effective diet trial can be challenging as it requires a high level of client and pet compliance, appropriate diet selection and correct interpretation of the provocative challenge. This narrative guides the clinician through the process, highlights potential pitfalls and specifies how these can be avoided to achieve a successful outcome.

Functional-Molecular Mechanisms of Sympathetic-Parasympathetic Dysfunction in PVC-Induced Cardiomyopathy Revealed by Dual Stressor PVC-Exercise Challenge

BackgroundThe significance of autonomic dysfunction in premature ventricular contraction–induced cardiomyopathy (PVC-CM) remain unknown. ObjectivesUtilizing a novel “dual stressor” provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model. MethodsIn 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling. ResultsExercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload. ConclusionsSympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.

Efficacy of nonsolvent flower pollen extracts in healthy women with urinary incontinence: A randomized, double-blind, placebo-controlled, parallel study.

Urinary incontinence (UI) is a debilitating and common condition that adversely affects quality of life. Prescriptive and surgical approaches for managing UI symptoms may result in undesirable risks and complications. This randomized, double-blind, placebo-controlled, parallel study investigated the efficacy of 2 nonsolvent flower pollen extracts on UI in healthy women. One-hundred and fourteen women aged 40-75 years who scored ≥5 on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) were randomized to receive either Graminex® RCT Fem™ UI, Graminex® PollenBerry®, or placebo for 24 weeks. The primary outcome was the change in the ICIQ-SF score between the trial and placebo groups after 24 weeks of supplementation. The secondary outcomes included changes in the frequency of nocturia (recorded in 3-day void diaries) and 24-hour leakage volume (assessed via pad weight) after 6, 12, 18, and 24 weeks of supplementation and changes in stress-induced urinary leakage volume (after completion of a provocative maneuver challenge) after 24 weeks of supplementation. All the groups demonstrated improvement in ICIQ-SF scores at week 24 (p < 0.001). The RCT Fem™ UI group had the greatest improvement in ICIQ-SF scores (-4.07 ± 3.4), followed by the PollenBerry® group (-3.34 ± 2.87) and placebo group (-2.61 ± 3.52). The RCT Fem™ UI group had corresponding improvements in 24-hour leakage volume (-17.68 ± 39.84 g) and frequency of nocturia (-0.52 ± 1.26) (p ≤ 0.05). PollenBerry® supplementation significantly improved stress-induced urinary leakage volume (-7.12 ± 15.64 g) at week 24. The study products demonstrated safe hematological and chemical profiles. RCT Fem™ UI supplementation resulted in significant and clinically meaningful reductions in UI severity, with corresponding improvements in daily urinary leakage volume and frequency of nocturia. PollenBerry® significantly improved stress-induced urinary leakage volume, suggesting that it may be efficacious in women who are prone to stress UI. The study products were safe and well tolerated in this population.

Outpatient and primary care direct provocation challenges for antibiotic allergy in children

ObjectiveTo evaluate the use of a questionnaire-based decision-making algorithm to triage children with reported antibiotic allergies to proceed directly to an oral provocation challenge.DesignCohort study.SettingChildren aged 2–16 years attending paediatric...

ОСОБЕННОСТИ ДИСТАНЦИОННОГО МЕНЕДЖМЕНТА КАК НОВОЙ ФОРМЫ УПРАВЛЕНИЯ ПЕРСОНАЛОМ

Digitalization and information and communication technologies have led to significant structural changes in the development of the economy. The labor market is no exception, and its dynamics are changing significantly as a result of these transformations. One of the key components of the structural shift in employment is the spread and development of remote work. This form of labor organization is becoming more and more in demand and an integral part of the digital economy, which determines the special nature and working conditions that allow you to work remotely. Remote work offers new opportunities and benefits for both employers and employees. It allows companies to expand the geographical coverage of their operations, attract specialists from all over the world and reduce the cost of renting office space. At the same time, remote work gives employees flexibility in choosing a workplace and work schedule, facilitating communication and collaboration over the Internet. At the same time, the proliferation of remote work also raises provocative questions and challenges. For example, how to ensure the security and protection of data when working remotely? How to create effective tools and environments for remote collaboration? What issues of internal communication and corporate culture arise in a remote work environment? Researching this topic will help you better understand these challenges and identify the most effective practices for organizing remote work. Moreover, it can help shape policies and strategies aimed at maintaining a balance between flexibility and productivity in the new digital economic order.

Is it time to abandon the theory of Democracy? The problem with the people: Afterword to the Foreword by Sergio Verdugo

Abstract Sergio Verdugo’s provocative Foreword challenges us to think about whether the concepts we inherited from classical constitutionalism are still useful for understanding our current reality. Verdugo refutes any attempt to defend what he calls “the conventional approach to constituent power.” The objective of this article is to contradict Verdugo’s assertions which, the Foreword claims, are based on an incorrect notion of the people as a unified body, or as a social consensus. The article argues, instead, for the plausibility of defending the popular notion of constituent power by anchoring it in a historical and dynamic concept of democratic legitimacy. It concludes that, although legitimizing deviations from the established channels for political transformation entails risks, we must assume them for the sake of the emancipatory potential of constituent power.

HARKing can be good for science: Why, when, and how c/should we Hypothesizing After Results are Known or Proposing research questions After Results are Known

AbstractThis provocation challenges the current view that practicing HARKing (Hypothesizing After Results are Known) must be avoided under all circumstances. I explain why and under which circumstances scholars may be allowed, even encouraged, to follow this practice. I use the extant literature and specific cases to show how HARKing can help generate new and worthy knowledge, and why an outright ban on HARKing is wrong for the field of social sciences—and, particularly, for business and management studies. The argument expands the phenomenon to PARKing too (Proposing research questions After Results are Known). The implications for knowledge creation are critical because this practice could hinder research and might defy logic. This provocation is intended as a thought‐provoking exercise, hopefully leading to changes in the approach and mindset of scholars. HARKing could offer a major added value to the field as it helps to develop knowledge that, so far, has been blocked by attempts to ban HARKing, and thereby may help open new avenues for knowledge creation.

An open-label clinical trial to evaluate the efficacy of an elemental diet for the diagnosis of adverse food reactions in dogs.

The diagnosis of cutaneous adverse food reactions (CAFR) in dogs is dependent on a diet trial and provocative challenge. To evaluate the efficacy of an elemental diet for the diagnosis of CAFR in dogs. Sixty-two client-owned nonseasonally pruritic dogs. A prospective, uncontrolled, observational elimination diet trial study. Dogs were fed a commercially available elemental canine diet (Pro Plan Veterinary Diets EL Elemental Canine Formula, Nestlé Purina PetCare Company) for up to eight weeks. Pruritus was assessed using a validated Visual Analog Scale (PVAS), lesions with the Canine Atopic Dermatitis and Severity Index, 4th iteration (CADESI-04) and gastrointestinal (GI) signs with a client questionnaire. All dogs were challenged with their previous diet for up to 14 days. Treats were added from Day (D)7 to D14. Forty-five dogs completed the study. Eighteen (40%) of these were diagnosed with CAFR and 27 (60%) were diet-nonresponsive (NR). Dogs with CAFR flared on provocative challenges within 14 days. The smallest volume of previous diet that induced a CAFR flare was one teaspoon in two dogs (11.1%). The mean number of days leading to a provocation of clinical signs was 4.88 days. Gastrointestinal signs improved in both groups. Eight of the dogs with CAFR (44.4%) were subsequently maintained on the elemental diet alone. Pro Plan Veterinary Diets EL Elemental Canine Formula is efficacious for the diagnosis of canine CAFR. One teaspoon of the offending diet may induce clinical signs in some dogs with CAFR.

Alternative Scale(ing) Practices in Architectural Design Studio

Commonly associated with the accurate representation of reality according to a specific ratio, which depends mainly on measuring and precision, the notion of scale has been considered an operative tool in architecture to perceive and indicate the size of anything according to a reference system. An effort to challenge the concept of scale(ing) to include diverse reference units and their scalar articulations holds the potential of instigating novel associations in architectural design studios. Possible readings of these alternative scale(ing) conditions are discussed in the paper in reference to a series of design exercises conducted at architectural design studios. The main intention is to question these unmediated associations to the reference unit in the determination of size and proportion, thus possible scales of architectural space. This particular method of analysis aims to arrive at various scale(ing) conditions, whose internal reference system is challenged by the changes and shifts in the definition of the major reference unit. Each different scale(ing) condition studied through the given exercise was regarded as an act of confrontation for readings of scale as well as presenting provocative challenges to the architectural design processes. With this standpoint, the paper proposes a multi-layered reading of scale that argues the reference unit’s instrumentality in the definition of architectural space and proposes an alternative methodology of integrating scale in architectural design education.

PO-01-031 TO CHECK OR NOT TO CHECK: LACK OF FIRST PASS ISOLATION MAY IDENTIFY PATIENTS WHO WOULD BENEFIT FROM PROVOCATIVE PHARMACOLOGIC CHALLENGE DURING PULMONARY VEIN ISOLATION

Durable pulmonary vein isolation (PVI) is the cornerstone of successful ablation of atrial fibrillation. Adenosine and isoproterenol are two commonly used pharmacologic agents for assessing conduction recovery during PVI. However, the use of a provocative pharmacologic challenge (PPC) is highly operator dependent, and the effect on outcomes after PVI using contemporary methods is unclear. Additionally, first pass isolation (FPI) has recently gained recognition as a marker for durable PVI. We sought to explore the utility of a PPC depending on the achievement of FPI. To assess the utility of a PPC with either adenosine or isoproterenol in patients with or without FPI during PVI. The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and PsAF Using Novel Contact Force Technologies registry (Real-AF) is a prospective, observational, multicenter registry of patients undergoing radiofrequency (RF) ablation. A total of 910 patients with paroxysmal atrial fibrillation undergoing de novo ablation were included in this study and were retrospectively analyzed. Patients were divided into four groups based on whether FPI was achieved in both pulmonary veins and whether a PPC was performed. Atrial arrhythmia recurrence at one year was reported. A total of 590 patients (65.5%) had FPI and 313 (34.5%) did not. A PPC was performed in 488 (82.7%) of the FPI group and 258 (82.2%) of the no FPI group. Baseline covariates were compared using an analysis of variance (ANOVA), shown in Table 1. Left atrial diameter, CHADS2VAsc score, left atrial volume, procedure time, and total RF ablation time were significantly different among the four groups. Adjusted Kaplan-Meier curves are shown in Figure 1. Using a Cox-proportional hazards adjustment for baseline covariates, PPC was not associated with atrial arrhythmia free survival in the FPI group (p=0.145) (Figure 1A) but was associated with atrial arrhythmia survival in the no FPI group (p=0.025) (Figure 1B). In patients without FPI, the use of PPC resulted in similar outcomes as the FPI group (Figure 1C). In patients undergoing PVI who have FPI, performing a PPC does not improve atrial arrhythmia free survival at one year. However, in patients without FPI, a PPC is associated with improved atrial arrhythmia free survival at one year, leading to similar outcomes to patients who achieved FPI. This may have important implications for intraprocedural decision-making and procedural efficiency during PVI.Tabled 1Table 1. Baseline Demographics and Procedural Characteristics (PO-01-031).FPI and PPC (n=488)FPI and No PPC (n=102)No FPI and PPC (n=258)No FPI and No PPC (n=55)p-value (ANOVA)Ejection Fraction (%)57.4 ±7.558.3±8.557.7±6.457.7±6.40.337Left atrial diameter (cm)3.9±0.74.0±0.63.9±0.54.2±0.60.042Age (years)64.9±11.666.6±10.163.6±10.965.5±8.80.117Hypertension336 (68%)65 (63%)179 (69%)30 (54%)0.101Diabetes Mellitus69 (14%)20 (19%)41 (16%)10 (18%)0.508Congestive Heart Failure29 (6%)9 (9%)18 (7%)8 (14%)0.114Sex (Female)245 (50%)42 (42%)108 (42%)21 (38%)0.076CHADS2Vasc Score2.6±1.52.5±1.42.3±1.42.0±1.60.025Left Atrial Volume (cm3)84.6±26.188.4±28.985.2±22.1103.2±30.6<0.001Left Atrial Low Voltage Area (% of surface area)2.6±7.74.7±9.02.5±7.74.3±6.70.062Procedure time (minutes)74±35102±4094±42117±44<0.001Total Radiofrequency Ablation time (minutes)18±826±1125±1128±11<0.001 Open table in a new tab

Translation from the peripheries of world literature: The case of Khalid Khalifa’s Madīḥ Alkarāhiyya

Taking the translation of Khalid Khalifa’s 2006 novel مدیح الكر اھ یة [Madīḥ Alkarāhiyya] into English as a case study, this article examines the concept of translation from the periphery to the centre as a consecrating practice and as an avenue for cultural exchange between dominating and dominated literary fields. It draws on concepts from socionarrative theory and theories of paratext to examine the textual and peritextual framing strategies that Madīḥ Alkarāhiyya might have needed to undergo in order to move to the centre and obtain a permit for international circulation. Textual framing is examined through two strategies of selective appropriation of textual material, namely omission and lexical selectivity. Peritextual framing is examined through the powerful thresholds of peritextual devices crafted on the front and back covers of the published translation. A micro-level analysis of how the text has been translated, packaged, and circulated for the consumption of the Anglophone market showed that consecration and peripheralisation were indivisible practices. The translation of Madīḥ Alkarāhiyya was not as consecrating as one might have assumed. On the contrary, it was accompanied by a regressive counterweight that served to re-peripheralise the translated text when translation took place from peripheral to hypercentral languages. This poses a provocative challenge to the general conception of translation from the periphery as a consecrating practice and reveals the effects of power differentials within the circuits of cultural capital.

Virtually supported penicillin allergy de-labelling during COVID-19

BackgroundPenicillin allergy is a commonly listed medication allergy despite rare overall incidence. Many patients erroneously have this label, which has personal, health, and societal costs. Penicillin allergy delabelling requires an oral challenge, which can be a rate limiting step in the de-labeling process; this is even more relevant with the reduction of in-person visits during the COVID-19 pandemic.ObjectiveTo identify the utility and broader applicability of using a virtually supported platform, initially adopted given COVID-19 restrictions, to expedite penicillin oral provocation challenge and penicillin de-labeling in patients at low to moderate risk of immediate hypersensitivity reaction and based on shared decision making.MethodsPatients in Vancouver catchment area were referred for penicillin allergy and virtually assessed by the consulting allergist between July 2020 and April 2021. Those deemed appropriate for oral challenge based on the allergist consultant were offered the option of a virtual oral provocation challenge to oral amoxicillin in a subsequent virtual visit. Patients who agreed and were consented underwent a virtually supervised oral amoxicillin challenge during the second virtual visit. Findings are summarized in this case series.ResultsTwenty-three patients, both adult and pediatric, ranging from no to significant co-morbidities were consented and underwent the virtual challenge. One hundred percent of patients were successful with no reaction after an hour post virtual oral provocation challenge with amoxicillin.ConclusionVirtual medicine is likely to remain in the allergist’s practice. Virtually supported penicillin allergy delabelling, based on shared decision making and risk stratification, presents another pathway for penicillin allergy delabelling.

Newborn Babies and Nursing Jesus (1 Peter 2:2-3): The Petrine Metaphor’s Disruption of Patriarchal Renderings of God and the Child

In 1 Peter 2 the author utilizes a curious metaphor: “Like newborn infants, long for the pure, spiritual milk, so that by it you may grow into salvation–if indeed you have tasted that the Lord is good” (2.2-3). When this metaphor is disentangled from Pauline and patriarchal assumptions, it can be recognized on its own terms. This article demonstrates that here, despite repetitive obfuscation, the author invites Jesus communities to imagine themselves as newborn babies who nurse from Christ Jesus. Significant implications unfold from this first-century metaphor. While stubbornly resisted for centuries, the implications of the biblical metaphor of nursing from Jesus continue to flow with provocative challenge and sustenance.

Hyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon

Background/purposeLack of robust, feasible, and quantitative outcomes impedes Raynaud phenomenon (RP) clinical trials in systemic sclerosis (SSc) patients. Hyperspectral imaging (HSI) non-invasively measures oxygenated and deoxygenated hemoglobin (oxyHb and deoxyHb) concentrations and oxygen saturation (O2 sat) in the skin and depicts data as oxygenation heatmaps. This study explored the potential role of HSI in quantifying SSc-RP disease severity and activity.MethodsPatients with SSc-RP (n = 13) and healthy control participants (HC; n = 12) were prospectively recruited in the clinic setting. Using a hand-held camera, bilateral hand HSI (HyperMed™, Waltham, MA) was performed in a temperature-controlled room (22 °C). OxyHb, deoxyHb, and O2 sat values were calculated for 78-mm2 regions of interest for the ventral fingertips and palm (for normalization). Subjects underwent a cold provocation challenge (gloved hand submersion in 15 °C water bath for 1 min), and repeated HSI was performed at 0, 10, and 20 min. Patients completed two patient-reported outcome (PRO) instruments: the Raynaud Condition Score (RCS) and the Cochin Hand Function Scale (CHFS) for symptom burden assessment. Statistical analyses were performed using the Mann-Whitney U test and a mixed effects model (Stata, College Station, TX).ResultsNinety-two percent of participants were women in their 40s. For SSc-RP patients, 69% had limited cutaneous SSc, the mean ± SD SSc duration was 11 ± 5 years, and 38% had prior digital ulcers—none currently. Baseline deoxyHb was higher, and O2 sat was lower, in SSc patients versus HC (p < 0.05). SSc patients had a greater decline in oxyHb and O2 sat from baseline to time 0 (after cold challenge) with distinct rewarming oxyHb, O2 sat, and deoxyHb trajectories versus HCs (p < 0.01). There were no significant correlations between oxyHb, deoxyHb, and O2 sat level changes following cold challenge and RCS or CHFS scores.ConclusionHyperspectral imaging is a feasible approach for SSc-RP quantification in the clinic setting. The RCS and CHFS values did not correlate with HSI parameters. Our data suggest that HSI technology for the assessment of SSc-RP at baseline and in response to cold provocation is a potential quantitative measure for SSc-RP severity and activity, though longitudinal studies that assess sensitivity to change are needed.

New (Paradigms In) International Economic Law

ABSTRACT Since the birth of the Journal of International Economic Law (JIEL) in 1998, the foundations of international economic law have undergone multidimensional changes. Emerging political and economic challenges have shaped international economic law into becoming inherently dynamic; not only have new frameworks developed for analyses of international economic relations, but novel social and environmental aspects of government policy now also fall within the field’s ambit. These challenges have shaken the normative foundations of international economic law and new paradigms in this field of law have emerged. Recent developments addressing matters ranging from the climate crisis to the coronavirus disease 2019 pandemic signify a turn in the WTO from negotiating trade rules to addressing pressing concerns facing humankind. When JIEL was first established, civil society renewed its calls for the inclusion of social and environmental concerns in so-called ‘trade and …’ policies. Today, the interlinkages between trade and other issues form an integral part of the international trading system. These new challenges and shifts in economic policy bring (some) traditional understandings of international economic law into question, and challenge the various normative underpinnings of international economic law in three ways: first, in the rise of novel approaches to international economic norm creation; second, in the expansion of subject areas covered by international economic rules; and third, in the steady disintegration of the traditional binaries, such as those between hard and soft law, between public and private actors, and between human rights and investment. These three changes have further provoked the development of analytical frameworks to study these norms. The eclectic and wide-ranging contributions in this special issue offer insightful critiques and provocative challenges to the community of international economic law actors facing unprecedented problems as the Journal celebrates its twenty-fifth anniversary.

The Baby in the Brick: A More-Than-Representational Approach to Architectural Action and Intramural Burial at Çatalhöyük

This article reconsiders the association, common globally and ubiquitous in Neolithic Turkey, between dead bodies and domestic architecture. Residential burial has conventionally been handled in a representational framework. Buildings’ physical and meaningful aspects are analytically separated, so that they can act as ‘containers of meaning’ in funerary contexts and as concrete technologies in others. Here, a provocative dataset challenges this separation: infant bodies and curated remains buried against the bases of unstable Çatalhöyük walls, as if to reinforce them. Rather than asking what such bodies meant, I adopt a more-than-representational approach inspired by Mol’s (2002) ‘enacting ontology’ and Barad’s (2007) ‘agential realism’ that asks what bodies could do. Doing so extracts bodies and walls from separate domains of mortuary and mechanical action, and asks how they were enacted as objects within Neolithic practice. I trace practices that enacted walls and bodies in Neolithic worlds – making walls’ futures responsive to subsurface burial. This example raises broader implications for the way archaeologists investigate spatial aspects of mortuary practice, and mortuary aspects of architecture, and more broadly the way we determine what the objects of our study are.