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Introducción. Los pacientes con Covid-19 tienen el riesgo de presentar síndrome de dificultad respiratoria aguda, por lo que pueden requerir ventilación mecánica y traqueostomía. De este modo, la decanulación es un proceso importante que está a cargo del equipo rehabilitador. Objetivos. Describir y caracterizar el proceso de decanulación en pacientes traqueostomizados con COVID-19 para identificar posibles factores que influyen en su realización exitosa. Métodos. Estudio descriptivo transversal realizado en los pacientes que fueron sometidos a traqueostomía entre junio de 2020 y julio del 2021 en la Clínica de Alta Complejidad Santa Bárbara de Palmira, Colombia. Las variables categóricas se presentaron con porcentajes y para las cuantitativas se contrastó la hipótesis de normalidad a través de la prueba de Kolmogorov-Smirnov. Resultados. Los pacientes, al momento de ingreso, tenían características de severidad, con un promedio de PaO2/FiO2 de 99,7 mmhg y bloqueo neuromuscular hasta por 20 días; el tiempo promedio de ventilación mecánica fue 17,3 días. A todos los pacientes el equipo de rehabilitación les realizó intervención; de los 15 pacientes incluidos, tres no fueron decanulados. Se realizó un análisis descriptivo de los objetivos y de la interven- ción realizada por cada disciplina; para los tres pacientes no decanulados se analizaron las principales barreras y los predictores del fracaso de una decanulación. Conclusión. Gracias a la instauración de un plan constante y activo de rehabilitación multidisciplinario en el que los pacientes reciben intervención desde su ingreso hasta su egreso se logró decanular de manera exitosa al 80% de los pacientes traqueostomizados.

GUARD Archaeology Ltd were commissioned by Scottish Water to undertake an archaeological watching brief during ground works associated with the installation of a waste water outfall and associated Combined Sewer Outflow (CSO) as part of development works at Castlebank Street, Partick. Earlier adjacent archaeological works had identified a large ditch and sandstone well on the periphery of the area to the south-west ( Green 2019 ). The archaeological watching brief included the initial monitoring of borehole drilling, expanding to all overburden stripping along the full length of the working area for the drainage tract as well as the adjacent CSO area, stretching from the existing River Kelvin's edge to the boundary of Castlebank Street. The works identified the remaining extent of previously identified features, along with a wide range of further features of interest. These consisted of several distinct phases of structural stonework and two substantial intersecting ditches; a substantial assemblage of pottery was also recovered, along with several metal objects including a medieval decorative pin and a copper alloy decorative boss. The stonework likely relates to the seventeenth century Hutcheson's tower house, with some of the earlier deposits, pottery and metal objects possibly originating from activity around the earlier twelfth century Bishops' residence. Bore hole monitoring was undertaken in early 2016, while overburden stripping and archaeological excavation took place between February and August 2016.

How does faith matter in today's business world? Family businesses are the dominant organizational form globally. Yet, religion in family firms has been under-researched for many years, with only limited articles published in the past two decades. While our study focused on the Christian faith, we recognize the contributions of other religions to family businesses. The significant influence of faith needs to be better understood by Christians and others alike to promote harmonious relationships within and between faith groups. In a qualitative study, we examine the utilization of faith-led values among the owners of 15 U.S. multigenerational family firms, using a grounded theory approach and the theoretical lens of family systems theory. We analyzed the reported perceptions of 33 family firm owner-manager and family-manager respondents, focusing on the impact of faith on relationships with stakeholders, including, but not limited to family members, employees, and customers. These perceptions were based on the respondents' faith, their practice of prayer at work, prayer for the business, and the acknowledgment of God's power. Therefore, we propose that a faith system is central for such family firm leaders in addition to the family, business, and ownership systems. We depict the faith system as the hub of a wheel with spokes representing the family, business, and ownership systems driving the family firm. We summarize our findings with six propositions.

The international Sickle Cell World Assessment Survey (SWAY) reported a high impact of sickle cell disease (SCD) on patients' daily lives globally. In this study, we analyzed whether the reported burden differed between patients from the USA (n = 384) and other high-income (HI; n = 820) or low- to middle-income (LMI; n = 941) countries. We assessed symptoms and complications, incidence/management of vaso-occlusive crises (VOCs), treatment utilization/satisfaction, and the impact of SCD on education/employment. Certain symptoms (bone aches, insomnia, and joint stiffness) and complications (swollen/painful fingers/toes, gallstones, vision problems, blood clots, and asthma) were reported proportionally more by patients in the USA than in the HI/LMI countries. Self-reported VOCs were more common (mean [SD]: 7.1 [5.7] vs. 5.5 [8.9] and 4.4 [4.6] in the previous 12 months) and were managed more often by hospitalization (52% vs. 24% and 32%) in the USA than the HI and LMI countries. A higher proportion of patients from the USA than the HI/LMI countries reported a negative impact of SCD on their employment/schooling. Although high overall satisfaction with current treatments was reported globally, most patients indicated a strong desire for alternative pain medications. There are likely several reasons for the relatively high patient-reported burden in the USA group compared with the HI/LMI countries, including an older population and differences in newborn screening programs and pediatric/adult transition of care. It is clear that there is an urgent need for improved understanding and management of SCD globally, not just in the USA.

Introducción: El COVID-19 ha generado retos por la alta demanda de servicios, haciendo necesario buscar alternativas de soporte ventilatorio que permitan responder a las necesidades de la población.Es importante disponer de herramientas que permitan detectar precozmente el fracaso de estrategias ventilatorias no invasivas e identificar tempranamente la necesidad de intubación. Objetivo: identificar las variables asociadas a fracaso en el tratamiento con cánula de alto flujo (CNAF) en pacientes con COVID-19. Materiales y Métodos: estudio observacional analítico, corte transversal con 68 pacientes de la unidad de cuidados intensivos con COVID-19, que recibieron tratamiento con CNAF. Las variables de estudio se evaluaron en tres momentos, a las 24, 48 y 72 horas, llevando a cabo un análisis bivariado y multivariado entre los que fracasaron y los que tuvieron éxito. Resultados: en el análisis bivariado las variables que presentaron una relación estadísticamente significativa a las 24h fueron el no presentar un aumento del trabajo respiratorio (Wresp) (p=0.000) y saturación de oxígeno (SatO2) normal (p=0.006). A las 48h: no aumento en Wresp (p=0.014), SatO2 normal (p=0.005), presión arterial de oxígeno/fracción inspirada de oxígeno (PAFI) leve o moderado (p=0.039). A las 72h fracasaron: PAFI severa (p=0.000), aumento de Wresp (p=0.001) y el índice de ROX menor a 4.88 (p=0.023). De acuerdo con el análisis multivariado las variables predictoras de fracaso a las 24h fueron: FIO2, SatO2, Wresp y a las 48h FIO2 y SatO2. Conclusiones: el aumento de FIO2>70 %, presentar incremento del Wresp y SpO2 menor de 88 % son variables asociadas a fracaso de la CNAF y facilitan tomar decisiones clínicas sobre avanzar o no hacia un soporte ventilatorio invasivo.

The Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched actin at the cell cortex and thereby powering membrane protrusions that mediate cell migration. Here, using knock-down (KD) or knock-out (KO), we combine the inactivation of the Arp2/3 inhibitory protein Arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit, CYFIP2, that all enhance the polymerization of cortical branched actin (CBA). Inactivation of the 3 CBA negative regulators increases migration persistence of human breast MCF10A cells, and of endodermal cells in the zebrafish embryo, significantly more than any single or double inactivation. In the triple KO, but not triple KD cells, the “super-migrator” phenotype was associated with a heterogenous down-regulation of vimentin expression and a lack of coordination in collective behaviors, such as wound healing and acinus morphogenesis. Re-expression of vimentin in triple KO cells restored the normal persistence of single cell migration to a large extent, suggesting that vimentin down-regulation is one of the adjustments in gene expression through which the super-migrator phenotype is stably maintained in triple KO cells. Constant excessive production of branched actin at the cell cortex thus commits cells into a motile state through changes in gene expression.

Peer reviewed: True, Perceptions of, and attitudes toward, wildlife are influenced by exposure to, and direct experiences with, nature. Butterflies are a conspicuous and ubiquitous component of urban nature across megacities that are highly urbanized with little opportunity for human-nature interactions. We evaluated public familiarity with, perceptions of and attitudes toward butterflies across nine megacities in East and Southeast Asia through face-to-face interviews with 1774 urban park users. A total of 79% of respondents had seen butterflies in their cities mostly in urban parks, indicating widespread familiarity with butterflies. Those who had seen butterflies also had higher perceptions of butterflies, whereas greater than 50% of respondents had positive attitudes toward butterflies. Frequent visits to natural places in urban neighbourhoods was associated with (i) sightings of caterpillars, indicating increased familiarity with urban wildlife, and (ii) increased connectedness to nature. We found two significant positive relationships: (i) between connectedness to nature and attitudes toward butterflies and (ii) between connectedness to nature and perceptions of butterflies, firmly linking parks users' thoughts and feelings about butterflies with their view of nature. This suggests that butterflies in urban parks can play a key role in building connectedness to nature and consequently pro-environmental behaviours and support for wildlife conservation among urban residents.

The year 2014 culminates for Peru the last border dispute at the international level, and and only on this date can the territory of the Republic be configured in its entirety. During the 20th century international land boundary agreements were reached with significant territorial losses, compared to the surface with which the Republic of Peru was born; and in the second decade of the 21st century international maritime boundaries were defined even with the participation of the International Court of Justice in The Hague. Regarding the internal territorial organization, after two centuries of republican life, Peru still faces many challenges. Approximately 75% of its political-administrative districts do not have boundaries established by law and are configured solely on the basis of referential limits with consequent internal boundary differences and permanent decision-making based on territorial informality.The progressive creation of non-functional constituencies, with evident political nuances, also constitutes a challenge in the attempt to configure rational constituencies.Similarly, the inability to create political-administrative regions leads to the consolidation of departmental bureaucracies that use their powers to weaken the regionalization process. This research, using historical analysis, develops the most relevant processes of territorial configuration and reconfiguration that took place between 1821–2021, which explain the current territorial organization of Peru.

3D printing is being increasingly adopted in radiation oncology for printing highly conformal medical devices for treatment. Optical surface reconstruction technologies have been shown to be useful for 3D printing applications due to their higher spatial resolution, non-ionising radiation imaging and will likely supplement existing radiographic imaging techniques in the future.

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The Turks and Caicos Islands (TCI) have been affected by sargassum inundations, with impacts on the economy and environment. Sargassum removal can be costly, but sargassum use and valorisation may generate income and offset environmental damage. A significant barrier to the valorisation of sargassum is insufficient knowledge of its chemical makeup, as well as its seasonal variation and decay after stranding. The chemical characterisation of mixed sargassum and its constituent species and morphotypes (S. natans I, S.natans VIII and S. fluitans) collected from TCI between September 2020 and May 2021 and changes in the composition of sargassum decaying (over 147 days) were studied. High ash (24.61–51.10% dry weight (DW)) and arsenic (49–217 mg kg−1) could severely hamper the use of this seaweed for food or feed purposes. Although there was some reduction in arsenic levels in decaying sargassum, levels remained high (>49 mg kg−1). Biomethane production by anaerobic digestion (AD) is a potential option. Nevertheless, the exploitation of sargassum for biogas, either fresh or as it decays on the beach, is challenging due to low methane yields (

Purpose Using the theory of planned behavior as a theoretical base, this study aims to examine the effect of the personality attributes, risk-taking, creativity and locus of control on the entrepreneurial intentions of US business college students. The authors replicated previous studies from around the world but performed the research during the Covid-19 pandemic. Design/methodology/approach The authors surveyed 353 students, comparing those with entrepreneurial intentions (n = 213) versus those without entrepreneurial intentions (n = 140). Findings The authors found that risk-taking and creativity both significantly and positively predicted entrepreneurial intentions, but locus of control did not have a significant impact. Practical implications Contextually, the authors performed this study during the widespread complications of the Covid-19 pandemic. The authors advise business educators to initiate programs that encourage student entrepreneurship by nurturing creativity and offering educational resources that assist students in reducing the perceived risk of entrepreneurship. Originality/value The authors seek to increase awareness among business educators of the significance of entrepreneurship as a desirable career. The authors believe that one impact from the Covid-19 pandemic has been an expanded interest among students to start their own businesses. The authors propose that creative measures introduced into the business school curriculum by business educators will enhance students’ desire to take risks to create their own businesses.

Despite significant research interest in Norwegian penality, there remains much to be learned about how people in Norway experience life during and after punishment. This article is one of the first to explore the lived experience of desistance as narrated by Norwegian desisters. We analyse ‘small stories’ that either opened up or frustrated the co-creation of change, showing how desistance develops (or is stymied) at a micro level. Our analytical framework helped us understand our informants as active subjects navigating a complex terrain of psychological, relational and systemic processes. Informants described a long-term, unfinalized desistance process, leading in some cases to an extended experience of liminality and welfare supplication.

Cardiac dyads are the site of communication between the sarcoplasmic reticulum (SR) and infoldings of the sarcolemma called transverse-tubules (TT). During heart excitation–contraction coupling, Ca 2+ -influx through L-type Ca 2+ channels in the TT is amplified by release of Ca 2+ -from the SR via type 2 ryanodine receptors, activating the contractile apparatus. Key proteins involved in cardiac dyad function are bridging integrator 1 (BIN1), junctophilin 2 and caveolin 3. The work presented here aims to reconstruct the evolutionary history of the cardiac dyad, by surveying the scientific literature for ultrastructural evidence of these junctions across all animal taxa; phylogenetically reconstructing the evolutionary history of BIN1; and by comparing peptide motifs involved in TT formation by this protein across metazoans. Key findings are that cardiac dyads have been identified in mammals, arthropods and molluscs, but not in other animals. Vertebrate BIN1 does not group with members of this protein family from other taxa, suggesting that invertebrate BINs are paralogues rather orthologues of this gene. Comparisons of BIN1 peptide sequences of mammals with those of other vertebrates reveals novel features that might contribute to TT and dyad formation. The analyses presented here suggest that the cardiac dyad evolved independently several times during metazoan evolution: an unexpected observation given the diversity of heart structure and function between different animal taxa. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.

Mechanical constitutive models of metals can be difficult to validate without loss of generality. Creep-induced stress relaxation in stainless steels is one such example: stress triaxiality may play a role in the deformation rate but is challenging to measure experimentally. We aimed to determine whether the accuracy of constitutive laws for multiaxial deformation, particularly creep deformation, can be verified by measuring the evolution of the complete stress tensor at a point within a structure. Creep stress relaxation specimens of Type 316H stainless steel were exposed to 550 °C for different durations. We used time-of-flight neutron diffraction and finite element analysis to determine the complete stress tensors at points within the specimens, tracking their development as the residual stress field relaxed. Multiaxial stress relaxation of 316H occurs at 550 °C due to plasticity and creep, and can follow a non-proportional deformation path. In our measurements, over-determination of the elastic strain tensor using neutron diffraction was found to reduce stress uncertainty. A popular creep constitutive model for 316H, when used with finite element analysis, predicts slightly higher strain rates than were observed experimentally. Sequential neutron diffraction stress measurements can be used to validate material constitutive laws in situations involving multiaxial deformation. This could be used to substantiate models of plasticity, viscoelasticity and creep. The RCC-MR primary/secondary creep law for 316H stainless steel is conservative for cases involving a complex initial stress field.

When foreign policies of states are examined, pride of place often goes to what are called high politics: the politics of diplomacy and war. However, for most developing nations, especially those in the region of sub-Saharan Africa, economic foreign policy, or low politics, may be as, or even more, important. In fact, the foreign policies of African nations are often seen as an extension of strategies to consolidate domestic political power. African leaders routinely place themselves in charge of foreign policy as a means of controlling these resource flows as well as to create some autonomy from competing domestic political forces. This is not to say that external state forces do not impinge on the ability of leaders to stay in power; however, in sub-Saharan Africa, this has been less of a priority, perhaps with the significant exception of Ethiopia. This paper seeks to show that the general foreign policy perspectives of Ethiopia from 1991 to the present have been an extension of the leaders and ruling elites trying to obtain significant sources of financial resources by exploring the general trends of how Ethiopia has engaged in international flows of resources. Examining Ethiopian foreign policy on three levels—international, regional, and domestic—this paper explains how, despite being a potential regional hegemon, Ethiopia has significant problems stemming from domestic issues of poverty and legitimacy. Moreover, the Grand Ethiopian Renaissance Dam will be highlighted as a case to explore how it affects, and is impacted by, all three levels.

The organic crystal of p-aminoazobenzene has been grown using slow evaporation technique. The cell parameters of the harvested crystal have been characterized by X-ray diffraction analysis. The UV–VIS–NIR spectrum shows that there is no considerable absorption after 580 nm. The number of modes of vibrations has been found out using experimental and theoretical analyses. Using the Hirshfeld surface analysis, different intermolecular interactions are identified. The HOMO–LUMO shows that there is charge transfer take place within the molecule. Natural bond analysis (NBO) is used to determine the electron delocalization and conjugative interactions. Mulliken charge distribution reveals that the C3 and C6 atoms have a positive charge value when compared to other carbon atoms. Using the density of states (DOS) bonding and antibonding orbitals are executed. Molecular electrostatic potential (MEP) gives information about the hydrogen atom attached to the nitrogen atom have more positive potential. TGA/DTA has also performed for p-aminoazobenzene to find out the thermal stability.

The single crystals of pure and 1 mol% Co2+-doped sodium acid phthalate hemihydrate were grown by slow evaporation solution growth technique at room temperature (35 °C). Powder XRD analysis shows that the basic structure of the sodium acid phthalate hemihydrate crystal is unaltered due to Co2+ doping. The functional groups of the crystal were elucidated by Fourier transform infrared (FTIR) spectrum. The transmittance spectra show that the crystals have high transmittance in the entire visible–NIR region. Thermogravimetric curves show the decomposition temperatures as 118 °C and 124 °C for pure and doped crystals. Addition of metal ion increases the hardness of sodium acid phthalate hemihydrate crystal. The dielectric constant value of 1 mol% Co2+-doped crystal was found to be significantly less than that of pure crystal. Multiple-shot damage threshold was performed on (0 0 1) plane. NLO efficiency is increased as a result of metal Co2+ ion doping. The oval shaped etch pits are observed on both pure and doped crystals.

Voting in China’s grassroots elections is more of a ritual than a right. For most citizens especially in the urban areas, the results of the local elections have little effect on their lives. Indeed, despite the Chinese Communist Party (CCP) campaigns to get the vote out in local elections, voter turnout is relatively low especially among younger voters. Beyond local political campaigns to remind citizens of their duty to vote is the community pressure and engagement. How does community interaction influence voter turnout in authoritarian grassroots elections? That is, are more socially engaged citizens more likely to vote in ritual elections? Moreover, does community engagement mitigate the age gap in voter turnout in grassroots elections in China? Scant literature exits on the relationship between community interaction and ritual voting in authoritarian regimes. Using the 2013 Chinese General Social Survey, this paper finds that community interaction plays a significant role in voter turnout. In addition, young people, who interact with neighbors, are just as likely to vote as the more socially connected older residents. The results have important implications for political behavior as well as for the grassroots elections in China.

An emerging body of evidence indicates that short-term immersion in cold water facilitates positive affect and reduces negative affect. However, neural mechanisms underlying these effects remain largely unknown. For the first time, we employed functional magnetic resonance imaging (fMRI) to identify topological clusters of networks coupled with behavioural changes in positive and negative affect after a 5-min cold-water immersion. Perceived changes in positive affect were associated with feeling more active, alert, attentive, proud and inspired, whilst changes in negative affect reflected reductions in distress and nervousness. The increase in positive affect was supported by a unique component of interacting networks, including the medial prefrontal node of the Default Mode Network, a posterior parietal node of the Frontoparietal Network, anterior cingulate and rostral prefrontal parts of the Salience Network and Visual Lateral Network. This component emerged as a result of a focal effect confined to few connections. Changes in negative affect were associated with a distributed component of interacting networks at a reduced threshold. Affective changes after cold water immersion occurred independently of each other, supporting the bivalence model of affective processing. Interactions between large-scale networks linked to positive affect indicate integrative effects of cold-water immersion on brain functioning.

Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age 60 years, smoking history 20 pack-years, PaOOur retrospective cohort study separated 27 803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras.Three definitions-low PaOAdvanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO

A growing body of scholarship suggests that Indigenous peoples abstain from voting in national and subnational elections because of colonialism and so classic determinants of turnout do not apply. ...

A growing number of evidence-based interventions have offered treatment for adults with Borderline Personality Disorder. Dialectical Behavior Therapy and Mentalization Based Therapy are both evidence-based treatments initially developed for chronically suicidal adults and have been adapted for adolescents relatively recently. There is increasing interest in treatment for Borderline Personality Disorder traits for adolescents using these two therapies. This article provides the results of a review of treatment outcomes for Dialectical Behavior Therapy versus Mentalization Based Therapy for adolescents. These interventions target Borderline Personality Disorder symptoms, self-harm and suicidal behavior. Adolescents with Borderline Personality traits are at considerable risk for suicide or long-term negative adult psychosocial outcomes. In order to assist clinicians and service providers in choosing the most appropriate treatment, six main electronic databases were searched from inception to April 11, 2019, to identify relevant studies. Twenty-five studies were included in this review; twenty-one on Dialectical Behavior Therapy for Adolescents and four concerning Mentalization Based Therapy for Adolescents. Significant improvements in suicidal ideation, suicidal attempts, self-harm (with or without suicidal intention), Borderline Personality Disorder symptoms, depressive symptoms, trauma, behavior problems and general functioning were reported for both interventions. In addition to outcome comparisons, this review contrasts the theoretical background and implementation issues of these two important psychological treatments for adolescents with Borderline Personality Disorder symptoms.

This article presents some findings derived from the doctoral thesis entitled Subject Topos. The problem of space in psychoanalysis. The aim is to show how Lacan used the logic of ancient stoicism to solve the Freudian problems related to space, which posed difficulties both in locating the unconscious spatially, and in clearly establishing a conception of the body, thus solving the advantages derived from the limits imposed by Aristotelian logic and Newtonian mechanics. Resumo: Este artigo apresenta alguns achados derivados da tese doutoral intitulada Topos do Sujeito. O problema do espaço em psicanálise. O propósito é mostrar como Lacan se serviu da lógica do estoicismo antigo para solucionar os problemas freudianos relativos ao espaço, os quais colocavam dificuldades tanto para localizar espacialmente o inconsciente, como para estabelecer claramente uma concepção de corpo, resolvendo assim as aporias derivadas dos limites impostos pela lógica aristotélica e a mecânica newtoniana.

Background: The use of the 21-gene recurrence score assay (RS) has reduced chemotherapy (CT) administration in patients with hormone receptor (HR)-positive, HER-2 negative, lymph-node negative, early stage breast cancer (ESBC). Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancers. This study uses real world data to assess (1) the effect of RS testing on treatment decision making in patients with ILC and (2) the economic benefit of testing in this subgroup. Methods: From October 2011 to February 2019, a retrospective, cross-sectional, observational study was conducted on HR+, HER-2 negative, lymph-node negative, ESBC patients with ILC who had RS testing in Ireland. For the decision impact analysis, a survey of Irish breast medical oncologists presumed that, without RS testing, CT would be recommended to patients with histological grade (G) 2 and 3 tumours and not for G1 tumours. In accordance with TAILOR-x results, patients were classified overall as low risk (RS≤25) and high risk (RS>25) and patients ≤50 years old were low risk (RS 0-15), intermediate risk (RS 16-25), and high risk (RS>25). Data were collected from electronic patient records. Descriptive statistics were used. Cost data were obtained from the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 166 patients with ILC were identified. Mean age was 59 years. Mean tumour size was 2.3cm (range 0.7-5.8). The majority had G2 tumors (n=152, 92%) with a small number of G3 (n=7, 4%) and G1 (n=7,4%). Overall, 153 patients (92.2%) had a low RS (≤25), 12 (7.2%) had high RS (>25), and 1(0.6%) was unknown. All 12 patients with RS>25 had G2 tumours, 6/12 (50%) had tumour size >3cm, 4(33.3%) were PR+ and 8(66.7%) were PR negative. In 29/166 (17.5%) patients, aged ≤50 at diagnosis, RS was ≤15 in 16(55%), 16-20 in 6(21%), 21-25 in 5(17%), >25 in 1(3.5%) and unknown in 1(3.5%). The majority of these patients (27, 93%) had G2 tumours, 1 had G1 and 1 had G3. Post RS testing 124 patients (74.5%) had a change in CT recommendation; all from CT to hormone therapy. In total, only 35 patients (21%) received CT. In this group, RS was 0-15 in 3(9%), RS 16-25 in 19(54%), RS >25 in 12 (34%) and unknown in 1(3%). Eight of 35 patients (23%) were aged ≤50. The most common CT regimen administered was docetaxel plus cyclophosphamide (TC). RS testing achieved a 78% reduction in chemotherapy use. This resulted in savings of €900,000 in treatment costs. With the incorporation of the assay cost, the net savings totalled approximately €400,000. Conclusions: Ireland was the first public health care system to reimburse the 21-gene recurrence score assay in Europe. There is limited evidence demonstrating the benefits of RS in ILC. In our study, the use of the test has resulted in a 78% reduction in chemotherapy use in an Irish ILC patient population and a substantial cost saving (greater than €400,000) to the Irish Healthcare System. Citation Format: Mehala Tharmabala, Lynda McSorley, Fathiya Al Rahbi, Evoy Denis, James G Geraghty, Rothwell Jane, Damian McCartan, Enda McDermott, Maccon M Keane, John Kennedy, Seamus O'Reilly, Steve Millen, John Crown, Lilian Mary Smyth, Catherine Margaret Kelly, Prichard Ruth, Cecily Quinn, Janice M Walshe. An analysis of the clinical and economic impact of the 21-gene recurrence score (RS) in invasive lobular early-stage breast cancer (ESBC) in Ireland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-23.

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve. Achieving autonomic engagement was accompanied by improvement from baseline in six-minute walk duration (6MWD), health-related quality of life, and left ventricular EF (LVEF), over and above those achieved by concomitant guideline-directed medical therapy (GDMT) administered to counteract harmful neurohormonal activation, with relative freedom from deleterious effects. Autonomic engagement and positive directional changes have persisted over time, and an exploratory analysis suggests that improvement in autonomic tone, symptoms, and physical capacity may be independent of baseline NT-proBNP values. Based upon these encouraging observations, prospective, randomized controlled trials examining the effects on symptoms and cardiac function as well as natural history have been warranted. A multi-national, large-scale, randomized, controlled trial is well underway to determine the outcomes associated with ART using autonomic nervous system engagement as a guide for VNS delivery.

This paper examined the challenges experienced in low-income areas with specific emphasis on Khayelitsha, Cape Town. The paper argues that low-income areas in most cities are faced with enormous challenges, including amongst many others, crime, overcrowding, sanitation, health issues, floods, and shack fires. These challenges are the byproduct of poor/colonial and/or urban planning practices or institutional inertia/neglect from municipalities and skewed service provisions. Moreover, these challenges account for the spread of environmental health diseases like diarrhea, dysentery, pneumonia, and tuberculosis. It is furthermore argued that these areas are also associated with substance abuse, alcoholism, and prostitution. The objective of this paper is to highlight these challenges in Low-Income Areas and their implications. Interestingly, existing scholarship has barely mentioned these problems without intensely explaining their underlying implications. It is these lacunae or gaps in the extant literature that this current study will seek to address as it illuminates these implications. To gain these insights the study utilised ethnographic qualitative research and observations conducted from March 2018 to October 2019 utilising a sample of 28 individuals. The study found that these challenges impacts on the residents culminating in illness, loss of livelihoods, and lives, and also property. This rationalises the study as it seeks to influence policy and ensure a change in attitudes in these areas.

Police violence against citizens is a common knowledge in Nigeria and it is on thisbasis that the prevalent public perception for the members of the force has generally been that of consternation, hatred and calumny. The police are regarded as violent extortionists, torturers, unfriendly, thieves, murderers, retched, undesirable, nuisance and the likes. The study focused on the need for adequate funding as a means of cubing the inimical behaviour observed among the force members. The article argues that to arm poorly remunerated Nigerian police men and women and send them to work among the public is to indirectly empower aggressively hungry men and women to extract money from the same people they are expected to protect. On this basis, it is recommended that the police trust fund law and the salary increment pronounced by the president since 2018 be implemented speedily with strict supervision

With quality function deployment (QFD) as its basis, the product design team is instrumental in promoting sustainability by incorporating relevant requirements in the early stages of the design process. The domain literature, however, contains significant gaps, especially for food products. First, the current literature fails to consider the requirements of all relevant stakeholders, which are crucial to sustainability. Second, while some offer various models of fuzzy QFD – multiple-attribute decision-making (QFD-MADM), they fail to comprehensively address the underlying interdependencies of decision parameters in the QFD. Furthermore, the majority of the works on QFD-MADM limit themselves to product planning while losing control over other subsequent phases of product development. Thus, this work attempts to advance these gaps by proposing an integrated multiphase fuzzy QFD-MADM framework that combines QFD, analytic hierarchy process (AHP), decision-making trial and evaluation laboratory (DEMATEL), and analytic network process (ANP) along with fuzzy set theory. A case study in a Philippine meat processing industry was implemented to demonstrate the proposed approach. The results of the case study show the crucial decision parameters for all phases, which would serve as inputs to design teams. Unlike previous models, the proposed framework preserves the transition of the priorities flow along with all four phases of product development. Thus, the stakeholder requirements are integrated into all product development stages, which is a strong indication that these requirements are addressed in each phase. Also, the proposed framework ensures that the uncertainty and the underlying complexities of interdependencies among decision parameters of the four phases of product design and development are addressed. The proposed framework contributes to sustainable product design literature in a manner that is comprehensive and analytical.

How insect communities are assembled in nature remains largely unknown. In particular, whether habitat filtering or competition serves as the main mechanism in forming insect communities is rarely subject to an in-depth investigation. One bottleneck lies in the difficulty of species identification when dealing with a large number of diverse insects. However, high-throughput sequencing technology coupled with classic DNA barcoding offers a great opportunity to infer community assembly for this speciose group. In this study, using 13,909 full-length barcodes obtained by Sanger sequencing or the full-length metabarcoding method (SOAPBarcode), we showed that competition was the main assembly mechanism for the moth communities in the younger Taihang Mountain, while habitat filtering for those in the old Yanshan Mountain. The two sequencing methods showed highly consistent results with regards to both diversity composition and community assembly mechanism. Significant phylogenetic signals and structure suggested that the focal moth communities were the result of the non-neutral assembly process, which was further confirmed by results of neutral assembly test that accounted for immigration and speciation rates. Our study showed that the full-length metabarcoding method can facilitate community assembly inferences, even for speciose taxonomic groups.

Interactions between plants and insects are among the most important life functions for all organism at a particular natural community. Usually a large number of samples are required to identify insect diets in food web studies. Previously, Sanger sequencing and next generation sequencing (NGS) with short DNA barcodes were used, resulting in low species-level identification; meanwhile the costs of Sanger sequencing are expensive for metabarcoding together with more samples. Here, we present a fast and effective sequencing strategy to identify larvae of Lepidoptera and their diets at the same time without increasing the cost on Illumina platform in a single HiSeq run, with long-multiplex-metabarcoding (COI for insects, rbcL, matK, ITS and trnL for plants) obtained by Trinity assembly (SHMMT). Meanwhile, Sanger sequencing (for single individuals) and NGS (for polyphagous) were used to verify the reliability of the SHMMT approach. Furthermore, we show that SHMMT approach is fast and reliable, with most high-quality sequences of five DNA barcodes of 63 larvae individuals (54 species) recovered (full length of 100% of the COI gene and 98.3% of plant DNA barcodes) using Trinity assembly (up-sized to 1015 bp). For larvae diets identification, 95% are reliable; the other 5% failed because their guts were empty. The diets identified by SHMMT approach are 100% consistent with the host plants that the larvae were feeding on during our collection. Our study demonstrates that SHMMT approach is reliable and cost-effective for insect-plants network studies. This will facilitate insect-host plant studies that generally contain a huge number of samples.

PurposeDynamic capabilities (DCs) help media firms adapt to rapidly changing environments. The purpose of this study is to provide a comprehensive literature review of studies of DCs in strategic management research with a view to understanding its implications for the management of media organizations. Essentially, it fertilizes on the idea that the concept of DC is useful and vital for answering various critical questions regarding the challenges that media organizations are currently facing.Design/methodology/approachThis study builds on a systematic literature reviewing design as the research methodology. It aims to identify, critically evaluate, and integrate factors, dimensions, and findings on studies of DCs in strategic management research and builds knowledge transfers to the field of strategic management research in the media industry.FindingsThe study shows that the DC framework helps media firms effectively respond to changing environments. The conceptual DC framework has implications for media strategy practice. Results indicate a considerable growth in the number of papers published related to the DCs in media organizations from 2003 to 2018.Originality/valueThe study qualifies the relevance and validity of the DC framework in strategic management research for the field of strategic media management. It explores a research agenda in this domain by precisely explaining the significant trends in the theory of DC to shape managerial strategies in the media industry.

Background: The 21 gene recurrence score (OncotypeDx ®) is reimbursed in Ireland to guide adjuvant treatment decisions for ER+, LN-negative, human epidermal growth factor receptor 2 (HER2)-negative BC. There is emerging evidence supporting the clinical utility of this test in patients with LN+ disease. Although the exact cut-off for chemotherapy has not been defined in this population, SEER data support the omission of chemotherapy for patients with RS Results: In total, 294 patients were enrolled across the - nine centres. Complete data is available on 123 patients (range 38 to 75, median 54 years), which included two male patients. Of the remaining 121 (98%) patients, 49 (40%) were premenopausal, 26 (21%) perimenopausal and 46 (37%) postmenopausal. The median tumour size was 38 mm (Range 7 to 58 mm). There were 101 (82%) patients with invasive ductal carcinoma, 17 (14%) with lobular carcinoma and 5 (4%) classified as other breast histology. Seventeen patients (14%) had grade 1, 74 (60%) grade 2 and 32 (26%) grade 3 disease. There were 79 (64%) patients with 1 LN+, 35 (29%) with 2 LN+ and 9 (7%) with 3 LN+ status. Overall access to the 21 gene RS test led to a 32% reduction in chemotherapy, 112 (91%) to 72 (59%) patients. This was most notable in patients with ductal histology (91 vs 61) and grade 2 breast cancer (66 vs 41) representing a 24.4% and 20.3% reduction, respectively. Similarly patients with 1 LN+ (71 vs 46) and 2 LN+ (34 vs 21) represented a 20.3% and 9.7% reduction, respectively. This study also identified four patients aged less than 40, for whom chemotherapy was not recommended. The biggest reduction in chemotherapy occurred in women aged over 50 (62 vs 36) at 21.1%. Overall, in 65% of cases, medical oncologists deemed the RS test result significantly changed treatment recommendations. Conclusion: These findings are consistent with results from similar studies in other countries. Broader access to the 21-gene RS could result in a reduction in the use of chemotherapy in Ireland. Citation Format: William J Mullally, Dara Bracken-Clarke, Andrew Padmore, Seamus O'Reilly, Deirdre O’Mahony, Janice Walshe, John Kennedy, Rajnish Gupta, Cathy Kelly, Miriam O'Connor, Karen Duffy, Maccon Keane, Bryan T Hennessy, Patrick G Morris. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor positive (ER+), lymph node positive (LN+) breast cancer (BC) in Ireland: A national, multi-centre, prospective study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-56.

Introduction Breast cancer patients respond differently to neoadjuvant chemotherapy (NAC) based on hormone receptor subtype. Oestrogen receptor positive/Her-2 receptor negative (ER+HER-) patients respond poorest but the effect of progesterone receptor (PR) status on response within this group has not been elucidated. The aim of this study was to assess the impact of PR status on response to NAC in ER+HER- breast cancer patients. Methods All patients receiving NAC over a seven-year period (2011-2017) were retrospectively identified from a prospectively maintained database within a specialised breast referral unit. Clinicopathological details were collated for all patients found to be ER+HER-. Primary outcomes including breast complete pathological response (PCR) rate and axillary PCR rate were compared between patients found to be progesterone receptor positive and negative. Secondary outcomes including grade and presence of lymphovascular invasion were also assessed. Results 206 patients were identified (151 in the ER+PR+HER- group and 55 in the ER+PR-HER- group). When compared with the PR+ group, patients found to be PR negative were more likely to achieve a breast PCR (3.3% vs 25.4%; Chi Square test; p=0.001), which was confirmed on multivariate analysis (p=0.001).In patients who were initially node positive, PR negativity was associated with a higher rate of axillary nodal PCR compared to those found to be PR positive(12.2% vs 25.5%; Chi Square test; p=0.04). ER+PR-HER- patients were more likely to have higher grade tumours but not LVI. Conclusion Over a quarter of ER+HER- patients who are PR negative will have a complete pathological response to NAC in the breast and axilla. Such patients should be considered for NAC at diagnosis. Citation Format: Michael R Boland, Eanna J Ryan, Timothy Nugent, Darina Gilroy, John Kennedy, Dhaffir Alazawi, Terence J Boyle, Elizabeth M Connolly. Impact of progesterone receptor status on response to neoadjuvant chemotherapy in oestrogen receptor positive breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-11.

Despite the political turbulence of the Trump-Trudeau era, the US-Canada relationship remains workable on many policy fronts. Against this backdrop, this article explores this relationship by first...

Enteric protozoans Cryptosporidium spp. and Giardia duodenalis are among the leading causes of diarrhoea in children. These parasites have particular impact in low- and middle-income countries. In these countries, people often live in close contact with their animals, highlighting the potential role of zoonotic routes of transmission in disease spread. The occurrence and species/genotypes of Cryptosporidium and Giardia duodenalis infecting humans in Tigray, Ethiopia were investigated, along with the risk associated with infection. Stool samples from 249 asymptomatic people (4-80 years of age) in four rural districts in Tigray and 58 from symptomatic young children (1-33 months) attending health centres in Mekelle, Tigray's main city, were analysed for Cryptosporidium oocysts and Giardia cysts. Participants in the rural areas completed questionnaires regarding potential risk factors, with emphasis on livestock contact and sources of water. The occurrence of Cryptosporidium infection was 6% and 5% in people in the rural districts and young children from Mekelle, respectively; equivalent figures for Giardia infection were 29% and 14%. Molecular characterization of Cryptosporidium isolates revealed C. ubiquitum, subtype XIIa in a sample from rural districts, and C. hominis subtype IdA17 (1 sample) and IbA9G3 (2 samples) in infants from Mekelle with diarrhoea. For Giardia, Assemblage B predominated (22/25; 88%), but we also identified three samples with Assemblage A (AII). Our major finding was that, despite the close contact between people and livestock in our rural study sites, transmission of Cryptosporidium and Giardia between humans and their animals seems to be surprisingly uncommon. Our results are discussed in relation to other relevant studies, and also draws attention to the possibility that introduction of zoonotic species and/or subtypes, such as C. parvum, could have serious consequences for both human and animal health. As our study was conducted in Tigray, further investigation in different settings in Ethiopia could provide relevant information on transmission and zoonotic potential, and the potential for spread of zoonotic transmission. In addition, given the importance of these two parasites in causing diarrhoea in children, this information is vital for developing effective appropriate interventions against transmission that can be applied not only in Tigray or Ethiopia, but throughout Africa and beyond.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. Acurrent challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.