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Survivors of head and neck squamous cell cancers (HNSCC) frequently complain of taste dysfunction long after radiation therapy is completed, which contradicts findings from most sensory evaluation studies that predict dysfunction should resolve few months after treatment. Therefore, it remains unclear whether taste and smell function fully recovers in HNSCC survivors. We evaluated HNSCC survivors (n = 40; age 63 ± 12 years, mean ± standard deviation) who received radiation therapy between 6 months and 10 years before recruitment and compared their responses to those of a healthy control group (n = 20) equivalent in age, sex, race, smoking history, and body mass index. We assessed regional (tongue tip) and whole-mouth taste intensity perception using the general Labeled Magnitude Scale and smell function using the University of Pennsylvania Smell Identification Test (UPSIT). To determine possible differences between groups in retronasal smell perception, we used solutions of sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and caffeine in coffee and asked participants to rate perceived smell and taste intensities with and without nose clips. We found groups had similar UPSIT and taste intensity scores when solutions were experienced in the whole mouth. However, HNSCC survivors were less likely to identify low concentrations of bitter, sweet, or salty stimuli in the tongue tip relative to healthy controls. Our findings suggest persistent and subtle localized damage to the chorda tympani or to the taste buds in the fungiform papillae of HNSCC survivors, which could explain their sensory complaints long after completion of radiotherapy.

Amplifications and non-coding 3′ UTR mutations affecting NFKBIZ have been identified as recurrent genetic events in diffuse large B-cell lymphoma (DLBCL). We confirm the prevalence and pattern of NFKBIZ 3′ UTR mutations in independent cohorts and determine they are enriched in the ABC subtype as well as the recently described novel BN2/C1/NOTCH2 classes of DLBCL. Presently, the effects of and mechanism by which non-coding mutations can act as cancer drivers has been relatively unexplored. Here, we provide a functional characterization of these non-coding NFKBIZ 3′ UTR mutations. We demonstrate that the resulting elevated expression of IκB-ζ confers growth advantage in DLBCL cell lines and primary germinal center B-cells as well as nominate novel IκB-ζ target genes with potential therapeutic implications. The limited responses to targeted treatments in DLBCL, particularly those targeting the NF-κB axis, led us to investigate and confirm that NFKBIZ 3′ UTR mutations affect response to therapeutics and suggest it may be a useful predictive biomarker.Statement of SignificanceThrough functional characterization we reveal that non-coding NFKBIZ 3′ UTR mutations are a common driver in DLBCL, and mutation status may be a relevant biomarker to predict poor response to therapeutics targeting the NF-κB pathway.

Understanding the knowledge, attitudes, and practices pertaining to food insecurity among oncology registered dietitian nutritionists (RDNs) is critical to ensuring that cancer survivors have adequate nutrition-a fundamental component of successful treatment and recovery.To qualitatively assess oncology RDNs' knowledge, attitudes, and practices regarding the food access needs of their patients using a qualitative semantic approach to thematic analysis.The qualitative cross-sectional study was conducted from September 2018 to January 2019.Forty-one oncology RDNs working with cancer survivors in various clinical settings across the United States participated.Participants completed a semistructured, in-depth interview via telephone, lasting an average of 49 minutes.Two coders (primary and secondary) trained in qualitative thematic data analysis methods used a semantic approach to thematic analysis to analyze transcripts. A qualitative and mixed methods online coding program Dedoose was used to organize and analyze the data.Participants defined food insecurity (FI) as a lack of access to nutritious foods and a lack of resources to purchase nutritious foods. RDNs stated they believe FI is a serious problem in the United Staes, has a greater influence on cancer survivors than healthy individuals and they have specific concerns about FI among their own patients. Despite their concerns, most expressed that they do not use a validated tool to identify FI, nor were they aware that any exists. Only a small proportion of the RDNs stated that they regularly ask patients about their food access needs.Although Oncology RDNs have heard of FI, they do not routinely assess patients' food security status with a validated tool, nor do they consistently ask patients directly about their food access needs. These findings suggest there is a need for developing education and training opportunities for oncology RDNs to enhance their ability to screen for and address FI with their patients.

Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) &gt, 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p &lt, 0.001) increased, while circulating 8OHdG (−8.52 ± 19.05 ng/mL, p &lt, 0.001), fecal 8OHdG (−6.78 ± 34.86 ng/mL, p &lt, 0.001), and TNFα (−16.95 ± 60.82 pg/mL, p &lt, 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted.

Alzheimer’s disease (AD) is a current public health challenge and will remain until the development of an effective intervention. However, developing an effective treatment for the disease requires a thorough understanding of its etiology, which is currently lacking. Although several studies have shown the association between oxidative damage and AD, only a few have clarified the specific mechanisms involved. Herein, we reviewed recent preclinical and clinical studies that indicated the significance of oxidative damage in AD, as well as potential antioxidants. Although several factors regulate oxidative stress in AD, we centered our investigation on apolipoprotein E and the gut microbiome. Apolipoprotein E, particularly apolipoprotein E-ε4, can impair the structural facets of the mitochondria. This, in turn, can minimize the mitochondrial functionality and result in the progressive build-up of free radicals, eventually leading to oxidative stress. Similarly, the gut microbiome can influence oxidative stress to a significant degree via its metabolite, trimethylamine N-oxide. Given the various roles of these two factors in modulating oxidative stress, we also discuss the possible relationship between them and provide future research directions.

The objective of this study was to determine the test-retest reliability; construct and criterion validity; and test operating characteristics of a newly developed cognitive impairment risk factor screening instrument, the Alcohol and Drug Cognitive Enhancement (ACE) Screening Tool. Participants in the validation study were 129 adults with substance use disorder (SUD) enrolled in residential SUD treatment services and 209 normal controls. Test and retest data were available for 36 participants with SUD and 40 normal control individuals on the ACE Screening Tool. Test-retest reliability was excellent (ICC = 0.97). The ACE Screening Tool was significantly correlated with the Montreal Cognitive Assessment (MoCA), Behavior Rating Inventory of Executive Functioning-Adult Version (BRIEF-A), Test of Premorbid Functioning (TOPF) and Five Point Test, establishing construct validity. Criterion validity was established using a ternary severity variable constructed using results obtained on the MoCA and BRIEF-A. Test operating characteristics analysis showed 93% sensitivity, 46% specificity, 33% positive predictive power, and 96% negative predictive power using a cut-score of3. Those high levels of sensitivity and negative predictive power indicated that the tool would likely detect cognitive impairment when present and should therefore be considered suitable as an initial screening tool for cognitive impairment in individuals attending SUD services.

Gastroesophageal reflux disease (GERD) has a high worldwide prevalence in adults and children. There is uncertainty regarding medical versus surgical therapy and different surgical techniques. This review assessed outcomes of antireflux surgery versus medical management of GERD in adults and children, robotic versus laparoscopic fundoplication, complete versus partial fundoplication, and minimal versus maximal dissection in pediatric patients.PubMed, Embase, and Cochrane databases were searched (2004-2019) to identify randomized control and non-randomized comparative studies. Two independent reviewers screened for eligibility. Random effects meta-analysis was performed on comparative data. Study quality was assessed using the Cochrane Risk of Bias and Newcastle Ottawa Scale.From 1473 records, 105 studies were included. Most had high or uncertain risk of bias. Analysis demonstrated that anti-reflux surgery was associated with superior short-term quality of life compared to PPI (Std mean difference = - 0.51, 95%CI - 0.63, - 0.40, IThe available evidence regarding the optimal treatment of GERD often suffers from high risk of bias. Additional high-quality randomized control trials may further inform surgical decision making in the treatment of GERD.

In January 2020, I completed a book (Taming the Megabanks: Why We Need a New Glass-Steagall Act) analyzing the financial crises that precipitated the Great Depression of the 1930s and the recent Great Recession. My book argued that the world’s financial system was caught in a “global doom loop” at the beginning of 2020. Bailouts and economic stimulus programs during and after the global financial crisis of 2007-09 (GFC) imposed heavy debt burdens on most governments, and leading central banks were carrying bloated balance sheets. The rescues arranged by governments and central banks during the GFC created a widely-shared expectation that they would continue to intervene to ensure the stability of major financial institutions and important financial markets. That expectation encouraged speculative risk-taking by financial institutions and investors as well as dangerous growth in private and public debts. I warned that the global doom loop was planting the seeds for the “next” financial crisis, which could overwhelm the already strained resources of governments and central banks. The “next” global crisis began only two months later, in March 2020. The rapid spread of the Covid-19 pandemic caused governments in most developed countries to shut down large sectors of their economies and impose social distancing mandates. Many thousands of businesses closed, setting off a downward spiral in economic activity that paralyzed global financial markets. Investors, businesses, and financial institutions “scrambled for cash” and engaged in panicked “fire sales” of financial assets. Governments and central banks in the U.S. and other advanced economies adopted fiscal stimulus measures and financial rescue programs with a size, speed, and scope that far surpassed the emergency actions taken during the GFC. The pandemic financial crisis and the extraordinary responses of governments and central banks demonstrate that policymakers have not addressed the root causes of the GFC. Major financial institutions and financial markets remain highly unstable. They continue to underwrite rapidly rising levels of private and public debts based on their shared expectation of future government bailouts. Governments and central banks have expanded their “safety nets” far beyond banks and now protect the entire financial system, including short-term wholesale credit markets, systemically important nonbanks, and the corporate bond market. As a practical matter, governments and central banks have “bankified” the financial system, thereby undermining market discipline, stimulating dangerous asset bubbles, and increasing social inequality. Our financial system must be reformed so that it no longer promotes unsustainable booms, fueled by reckless growth in private debts, followed by destructive busts that require massive bailouts and huge increases in government debts. My recent book provides a blueprint for needed reforms, including a new Glass-Steagall Act. A new Glass-Steagall Act would break up financial giants by separating banks from the capital markets and by prohibiting nonbanks from financing their operations with functional substitutes for bank deposits. A new Glass-Steagall Act would establish a financial system that is more stable, more competitive, and more responsive to the needs of consumers, communities, and business firms. Properly implemented, a new Glass-Steagall Act would provide the most direct and practical way to break the global doom loop and end the toxic boom-and-bust cycles of the past quarter century.

This paper argues that graffiti can provide a form of socio-political commentary at the local level, and is a valuable, yet often overlooked, resource for scholars and policymakers in conflict-affected societies. Graffiti, in its many forms, can provide rich insight into societies, cultures, social issues, trends, political discourse, and spatial and territorial identities and claims. Thus, this, paper suggests that graffiti is a valuable source of knowledge in societies undergoing social and political transformation, to hear the voices of those often left out from the official discourses. Despite advances in the field of arts and international relations and the focus on the local and the everyday, peace and conflict scholarship and policy still lack systematic engagement with arts-based contributions and how to read them. The paper attempts to address this gap by outlining four core dimensions to consider when attempting to interpret and decode graffiti: the spatial, temporal, political economic and representative dimensions. This can also be viewed as an inquiry into the where, when, who and what. These four elements make up an analytical guide and enable scholars to better understand graffiti, and its political meaning and messaging.

OBJECTIVES: Associations between diet and colorectal cancer (CRC) have not yet been examined in a population inhabiting the Palestinian territories, which are undergoing a nutrition transition. Understanding how diet may impact CRC risk among Palestinians is essential to developing targeted, culturally-relevant strategies that could alleviate the burden of this disease. The aim of this study was to examine how dietary fiber and fruit & vegetable (FV) intakes are associated with the risk of CRC among Palestinian adults recruited from a tertiary care facility in East Jerusalem. METHODS: This was a case-control study of 528 Palestinian men and women >18 years old who were recruited from Augusta Victoria Hospital (AVH) between 2014 and 2016. Cases included 118 patients who were treated for CRC at AVH. Controls included 410 individuals who consisted of a community-based sample of Palestinian individuals without cancer. All participants completed a survey regarding demographics, CRC-related risk factors, and a validated food screener to assess intakes of dietary fiber and FV. Multivariable logistic regression models tested associations between dietary fiber and FV intakes (categorized into quartiles) with the risk of CRC, adjusting for sex, diabetes, family history of CRC, and inflammatory bowel disease. RESULTS: After adjusting for covariates, as dietary fiber increased across quartiles of intake, the risk of CRC significantly decreased (OR for Q4 vs Q1 = 0.26, 95% CI: 0.12–0.58, p-trend = 0.0007). There was no significant association observed between FV intake and CRC risk. CONCLUSIONS: Consumption of high dietary fiber was associated with lower CRC risk in this case-control study of a Palestinian population. The development and testing of culturally-relevant dietary interventions to promote increasing dietary fiber intake among Palestinians are needed, particularly interventions targeting those at high risk for developing CRC. FUNDING SOURCES: USDA/NIFA Hatch Project 1,011,487 and a Pears Foundation Scholarship from the Robert H. Smith Faculty of Agriculture, Hebrew University of Jerusalem.

BackgroundCLIPPER2 was an 8-year, open-label extension of the phase 3b, multicenter, 2-year CLIPPER study of the safety and efficacy of etanercept (ETN) in the treatment of patients (pts) with juvenile idiopathic arthritis (JIA) categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).ObjectivesThe objective of this analysis was to describe the safety of ETN in this population after 10 years of follow up.MethodsPts (n=127) with eoJIA (2-17 years), ERA, or PsA (each 12-17 years) who received ≥1 ETN dose (0.8 mg/kg once weekly [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. The primary outcome measure was the occurrence of malignancy. Long-term safety was assessed as the total incidence of events from CLIPPER baseline (BL) to month (mth) 120, frequency of events per 100 patient-years (EP100PY), and frequency of events in each study year.ResultsA total of 109/127 (86%) pts entered CLIPPER2; 99 (78%) continued in the active treatment period. At mth 120, 84 (66%) pts had completed the study; 27 (21%) while actively taking ETN; 7 (6%) had withdrawn from treatment due to low/inactive disease; 5 (4%) had re-started ETN following an earlier withdrawal from treatment; and 45 (35%) had stopped ETN (but remained under observation); 25 (20%) pts permanently discontinued from the CLIPPER2 study. In CLIPPER/CLIPPER2, 1 case of malignancy (Hodgkin’s disease) was reported (1 pt with eoJIA in Year 3). There was 1 case of uveitis (1 pt with eoJIA in Year 8) and 3 of Crohn’s disease (2 pts with ERA, Year 1/Year 6; 1 pt with eoJIA, Year 5). There were 2 cases of opportunistic infections (both herpes zoster), and no deaths. Overall, there were 559 (81.82 EP100PY) treatment-emergent adverse events (TEAEs) excluding infections and injection-site reactions (ISRs). The overall rate of TE serious infections was low (N=14; 2.05 EP100PY) (Table 1), with the most common TE serious infection being gastroenteritis (N=2; 0.29 EP100PY). The most frequently reported TEAEs (N [EP100PY]) were headache (28 [4.10]), arthralgia (24 [3.51]), pyrexia (21 [3.07]), diarrhea (14 [2.05]), and leukopenia (12 [1.76]). Overall, 39 patients reported serious AEs (excluding infections/ISRs). The number and frequency (N [EP100PY]) of TEAEs (excluding infections/ISRs) decreased over the 10-year study period from 193 [173.81] in Year 1 to 9 [27.15] in Year 10. The number and frequency of TE infections and TE serious infections also decreased over the 10-year study period. There was no clear trend of a decrease over time for the incidence of TE serious AEs (Figure 1).Table 1.ETN Safety Summary (from CLIPPER BL to mth 120), N (EP100PY) (FAS)*eoJIA, n=60(EXP=313.667 PY)ERA, n=38(EXP=206.971 PY)PsA, n=29(EXP=162.576 PY)Total, n=12(EXP=683.214 PY)TEAEs†269 (85.76)176 (85.04)114 (70.12)559 (81.82)TE serious AEs†16 (5.10)17 (8.21)7 (4.31)40 (5.85)TE ISRs23 (7.33)29 (14.01)12 (7.38)64 (9.37)TE infections418 (133.26)99 (47.83)155 (95.34)672 (98.36)TE serious infectionsǂ5 (1.59)4 (1.93)5 (3.08)14 (2.05)Opportunistic infections§01 (0.48)1 (0.62)2 (0.29)TEAEs causing withdrawal†7 (2.23)9 (4.35)2 (1.23)18 (2.63)TE infections causing withdrawal2 (0.64)01 (0.62)3 (0.44)*While on active ETN treatment or within 30 days of last dose†Excluding infections/ISRsǂGastroenteritis, 2 (0.29); acute tonsillitis, anal abscess, bronchopneumonia, gastrointestinal infection, helicobacter gastritis, influenza, peritonitis, pharyngitis, pyelocystitis, sepsis, urinary tract infection, viral infection, all 1 (0.15)§Both herpes zosterEXP, exposure to ETN; FAS, full analysis set; n, number of patients; N, number of eventsConclusionETN treatment to mth 120 was well tolerated in this patient population and consistent with the known safety profile. Frequency of TEAEs and TE infections decreased over time. Over 10 years, there was 1 reported event of malignancy and the overall rate of TE serious infections was low.References[1]NCT00962741/NCT01421069AcknowledgementsMedical writing support was provided by Iain McDonald, PhD, of Engage Scientific Solutions and was funded by Pfizer.Disclosure of InterestsJelena Vojinovic Speakers bureau: Abbvie, Roche, Sandoz, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Violeta Panaviene: None declared, Gordana Susic: None declared, Gerd Horneff Speakers bureau: Chugai, Eli-Lilly, Glaxo Smith and Kline, Janssen, Novartis, Pfizer, Roche and Sobi, Grant/research support from: Novartis, Janssen, Roche, Valda Stanevicha Speakers bureau: Sandoz, Abbvie, Roche, Katarzyna Kobusinska: None declared, Zbigniew Żuber: None declared, Bogna Dobrzyniecka: None declared, Jonathan Akikusa: None declared, Tadej Avcin Speakers bureau: AbbVie, Octapharma, and Takeda, Consultant of: AbbVie, Alexion, Octapharma, and Takeda, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Consultant of: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Cecilia Borlenghi Shareholder of: Pfizer, Employee of: Pfizer, Edmund Arthur Employee of: Pfizer, Svitlana Y Tatulych Shareholder of: Pfizer, Employee of: Pfizer, Chuanbo Zang Shareholder of: Pfizer, Employee of: Pfizer, Bonnie Vlahos Shareholder of: Pfizer, Employee of: Pfizer, Nicolino Ruperto Speakers bureau: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB., Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

BackgroundCLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study of the safety and efficacy of etanercept (ETN) in patients (pts) with juvenile idiopathic arthritis (JIA), categorized as extended oligoarticular JIA (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).ObjectivesEvaluation of the efficacy of ETN and its effect on health outcomes over 10 years of follow-up were secondary objectives and are reported here.MethodsPts (n=127) with eoJIA (n=60; 2-17 years of age), ERA (n=38; 12-17), or PsA (n=29; 12-17) who received ≥1 ETN dose (0.8 mg/kg once weekly [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. The study design has been reported previously.1 Efficacy endpoints included proportions of pts achieving JIA American College of Rheumatology (ACR) 30/50/70/90/100 criteria, Juvenile Arthritis Disease Activity Score (JADAS) inactive disease and clinical remission criteria, and sustained clinical remission (ACR criteria) or JADAS ≤1 for 12 continuous months (mths). Exploratory efficacy endpoints included time to flare following ETN withdrawal (based on ≥30% worsening in ≥3/6 ACR Pedi components, with ≥30% improvement in Observed Cases were used (i.e., there was no imputation for missing data) for pts who were in the Active Treatment Period.ResultsA total of 109/127 (86%) CLIPPER participants entered CLIPPER2 (n=55 eoJIA, n=31 ERA, n=23 PsA), with 99 (78%) pts continuing in the Active Treatment Period. Overall, 84 (66%) pts completed 120 mths of follow-up; 27 (21%) while actively taking ETN. Thirty (24%) pts entered the Withdrawal Period from the Active Treatment Period (i.e., they discontinued ETN, either by meeting the Wallace definition for clinically inactive disease for at least 6 months on ETN, or by having had a good clinical response and being deemed to benefit from withdrawal in the investigator’s judgment). Of the pts in the Active Treatment Period, over 90% achieved JIA ACR 50 response at all study time points. Sustained JADAS and ACR remission was achieved by 42 (33%) pts and 17 (13%) pts, respectively. The mean improvements from baseline in JADAS disease activity at mth 24 of CLIPPER were largely maintained through CLIPPER2 A total of 109/127 (86%) CLIPPER participants entered CLIPPER2 (n=55 eoJIA, n=31 ERA, n=23 PsA), with 99 (78%) pts continuing in the Active Treatment Period. Overall, 84 (66%) pts completed 120 mths of follow-up; 27 (21%) while actively taking ETN. Thirty (24%) pts entered the Withdrawal Period from the Active Treatment Period (i.e., they discontinued ETN, either by meeting the Wallace definition for clinically inactive disease for at least 6 months on ETN, or by having had a good clinical response and being deemed to benefit from withdrawal in the investigator’s judgment). Of the pts in the Active Treatment Period, over 90% achieved JIA ACR 50 response at all study time points. Sustained JADAS and ACR remission was achieved by 42 (33%) pts and 17 (13%) pts, respectively. The mean improvements from baseline in JADAS disease activity at mth 24 of CLIPPER were largely maintained through CLIPPER2.ConclusionThe low numbers of evaluable pts notwithstanding, efficacy results were consistent with the profile of ETN, and treatment responses were considered clinically meaningful and durable with long-term treatment.References[1]Foeldvari I, et al. Arthritis Res Ther 2019;21:125.[2]Trincianti C, et al. Arthritis Rheumatol 2021:73;1966-75.Trial Registration:NCT00962741/NCT01421069AcknowledgementsMedical writing support was provided by Iain McDonald, PhD, of Engage Scientific Solutions and was funded by Pfizer.Disclosure of InterestsJelena Vojinovic Speakers bureau: Abbvie, Roche, Sandoz, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Violeta Panaviene: None declared, Gordana Susic: None declared, Gerd Horneff Speakers bureau: Chugai, Eli-Lilly, Glaxo Smith and Kline, Janssen, Novartis, Pfizer, Roche and Sobi, Grant/research support from: Novartis, Janssen, Roche, Valda Stanevicha Speakers bureau: Sandoz, Abbvie, Roche, Katarzyna Kobusinska: None declared, Zbigniew Żuber: None declared, Bogna Dobrzyniecka: None declared, Jonathan Akikusa: None declared, Tadej Avcin Speakers bureau: AbbVie, Octapharma and Takeda, Consultant of: AbbVie, Octapharma and Takeda, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Consultant of: Aurinia, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche, Cecilia Borlenghi Shareholder of: Pfizer, Employee of: Pfizer, Edmund Arthur Employee of: Pfizer, Svitlana Y Tatulych Shareholder of: Pfizer, Employee of: Pfizer, Chuanbo Zang Shareholder of: Pfizer, Employee of: Pfizer, Vasileios TSEKOURAS Shareholder of: Pfizer, Employee of: Pfizer, Bonnie Vlahos Shareholder of: Pfizer, Employee of: Pfizer, Nicolino Ruperto Speakers bureau: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB., Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

Expansion and intensification of managed landscapes for agriculture have resulted in severe unintended global impacts, including degradation of arable land and eutrophication of receiving water bodies. Modern agricultural practices rely on significant direct and indirect human energy inputs through farm machinery and chemical use, respectively, which have created imbalances between increased rates of biogeochemical processes related to production and background rates of natural processes. We articulate how these imbalances have cascaded through the deep inter-dependencies between carbon, soil, water, nutrient and ecological processes, resulting in a critical transition of the critical zone and creating emergent inter-dependencies and co-evolutionary trajectories. Understanding of these novel organizations and function of the critical zone is vital for developing sustainable agricultural practices and environmental stewardship.

Since regaining its independence in 2002, nation-building has been the focus of much scholarly research on Timor-Leste. National identity construction is a crucial aspect of this process, yet the ways in which this identity is officially represented has been largely overlooked. This article takes the national flag of Timor-Leste as a case study to explore the ways in which a historic East Timorese national identity has been symbolically constructed and visually embodied. By considering the potency of flags in an East Timorese cultural context, and by analysing the origins of Timor-Leste's flag alongside that of the political party Fretilin (Frente Revolucionária do Timor-Leste Independente), it becomes clear that post-independence re-imaginings of its symbolism have rendered it a powerful national symbol in the contemporary nation-state.

How long-term dietary intake shapes microbiota composition and stability in young children is poorly understood. Herein, the temporal variability in stool microbiota composition in relation to habitual dietary patterns of 4- to 8-year-old children (n=22) was investigated. Fecal samples were collected at baseline, 6 weeks and 6 months. Bacterial composition and volatile fatty acids were assessed by 16S rRNA sequencing and gas-chromatography, respectively. Nutrient intake was assessed using 3-day food diaries and dietary patterns were empirically derived from a food frequency questionnaire. Using a factor loading of >0.45 for a food group to be a major contributor to the overall dietary pattern, two dietary patterns were found to be associated with distinct microbiome composition. Dietary Pattern 1 (DP1), characterized by intake of fish, protein foods, refined carbohydrates, vegetables, fruit, juice and sweetened beverages, kid's meals and snacks and sweets, was associated with higher relative abundance of Bacteroidetes, Bacteroides and Ruminococcus and lower abundance of Bifidobacterium, Prevotella, Blautia and Roseburia. Dietary Pattern 2 (DP2), characterized by intake of grains, dairy and legumes, nuts and seeds, was associated with higher relative abundance of Cyanobacteria and Phascolarctobacterium and lower abundance of Dorea and Eubacterium. Fruit and starchy foods were present in both patterns, but were more associated with DP1 and DP2, respectively. Temporal stability of microbiota over a 6-month period was associated with baseline dietary patterns. Understanding how dietary intake contributes to microbiota composition and stability in early life in important for dietary recommendations and designing clinical interventions for microbiota-associated diseases.