Predetermined Pathway Research Articles

Students’ conceptions and experiences of institutionalised curriculum for multilingual learning: the case of a dual-foreign-languages programme

ABSTRACT Whilst the existing literature on multilingual learning in curriculum has properly addressed a variety of instructional factors, few studies have been dedicated to investigating the influence of institutionalisation as a contextual, power-laden factor on multilingual curriculum which in turn influences multilingual learning. To fill this gap, this qualitative study examines undergraduate students’ conceptions and experiences of the institutionalised dual-foreign-languages programme of English and French in a Chinese university. The findings unveil how the institutionalisation of dual-foreign-languages learning, as mediated by specific curricular arrangements, imposed a predetermined pathway towards achieving predetermined curricular goals. In such institutionalised curriculum, students experienced and conceived dual-foreign-languages learning as a rigidly devised project, in which they were pressurised to conform to fixed curricular arrangements as well as their underlying ideologies, and in which they also agentically responded to the institutionalised curriculum with the initiative to reflect and negotiate. It is thus suggested that curriculum developers and administrators should be cautious about imposing curricular intentions that over-simplify multilingual learning dynamics which may impede learning instead of promoting it.

A policy analysis of how alkyl nitrites (poppers) became prescription-only in Aotearoa New Zealand.

Alkyl nitrites ('poppers') are a group of drugs that includes amyl nitrite, butyl nitrite, and isopropyl nitrite. Their use is prevalent among men who have sex with men (MSM), to enhance sexual comfort and pleasure. In Aotearoa New Zealand, all alkyl nitrites became prescription-only from March 2020. With alkyl nitrites no longer sold locally in stores, and no availability via pharmacies (even with a prescription), access has been significantly reduced. This decision was opposed by advocacy groups and people who use alkyl nitrites. This policy case study explores how this decision was made and impacts on MSM. We use policy formation theory; both policy framing and Multiple Streams Framework, to analyse factors that contributed to this regulatory decision. Analysis of issue framing by policy coalitions was undertaken through review of documents including submissions and committee minutes. Two policy coalitions emerged, which differed in their issue framing. The Medicines Classification Committee conveyed concerns about evidence limitations, and recommended reclassification. NGOs and people who use alkyl nitrites communicated that there was no evidence of harm from alkyl nitrite use in New Zealand, and thus, given that there was evidence of benefit, the status quo should be maintained and further regulatory responses were unnecessary. Pre-existing processes created a situation where alkyl nitrite scheduling came unexpectedly onto the New Zealand policy agenda, and set the issue onto a somewhat pre-determined pathway with limited policy choices available. As a drug policy case study, it appears that reclassification was initiated due to a policy process that did not enable or support plausible alternatives. While the purpose of the reclassification was to improve safety, there was no evidence of harm prior to reclassification, and the reduction in access is likely to have increased harm for MSM.

Difficulties in Adaptation of the Mother and Newborn via Cesarean Section versus Natural Birth-A Narrative Review.

Birth is a physiological act that is part of the morpho-functional economy of the maternal body. Each stage in the act of birth has a predetermined pathway that is neurohormonally induced and morpho-functionally established through specific and characteristic adaptations. Like maternity, childbirth also has an important impact on the maternal body as a biological structure and psycho-emotional behavior. Cesarean section performed at the request of the mother with no medical underlying conditions besides the prolonged hospitalization risk can also cause breathing problems in children, delayed breastfeeding, and possible complications in a future pregnancy. Vaginal birth remains the path of choice for a physiological evolution pregnancy. Although erroneously considered safe and easy today, cesarean section delivery must remain an emergency procedure or a procedure recommended for pregnancies where birth is a risk to the mother and to the child, as cesarean section itself is a risk factor for negative outcomes for both mother and baby. This review summarizes the impact that both cesarean section and natural birth have on mother and newborn in their attempt to adapt to postpartum events and extrauterine life.

'We would have missed out so much had we terminated': What fathers of a child with Down syndrome think about current non-invasive prenatal testing for Down syndrome.

Non-invasive prenatal testing (NIPT) allows early, accurate diagnosis of Down syndrome that has resulted in increased terminations. This qualitative study involved in-depth interviews of fathers of children with Down syndrome about their views on the availability of NIPT. Thematic network analysis revealed that although fathers appreciated an early diagnosis with NIPT, they saw the test as being a predetermined pathway to termination. Fathers felt that expectation to terminate reflects negative societal attitudes towards those with Down syndrome and disability, fearing that NIPT may become a form of eugenics. Fathers retrospectively contrasted these attitudes with the actual reality of raising their children with Down syndrome, which they described as bringing joy to their lives. Findings suggest that although fathers valued NIPT as an information-giving tool that allowed autonomous parental choices about the pregnancy, they believe that it should be accompanied by balanced information about the reality of raising a child with Down syndrome.

Long-Term Regional Landscape Change in the Northern Tequila Region of Jalisco, Mexico

ABSTRACTThe Tequila Valleys, in Jalisco, Mexico, are well-known in archaeology for an early complex society known as the Teuchitlán tradition (350 b.c.–a.d. 450/500), but later developments have received little attention. Here I report on the first systematic, full-coverage survey of the Tequila region north of the Tequila volcano. I explore the ways in which the societies that occupied this territory experienced sociopolitical change diachronically by investigating settlement scale, integration, complexity, and boundedness. Through the use of these core features, I analyze how each changed in varying ways, resulting in patterns that do not conform to static societal categories. Interestingly, there is no evidence that a large polity controlled the entire region at any point in the sequence. Results indicate a dynamic sociopolitical landscape that did not develop along any predetermined pathway.

Copy-number and targeted sequencing analyses to identify distinct prognostic groups: Implications for patient selection to targeted therapies amongst anti-endocrine therapy resistant early breast cancers.

524 Background: Hormone receptor positive breast cancer is a therapeutic challenge. Despite optimal anti-endocrine therapies, most breast cancer deaths follow a diagnosis of early luminal cancer. To understand the impact of multiple aberrations in the context of current therapy, we assessed the prognostic ability of genomic signatures as a putative stratification tool to targeted therapies. Methods: This a priori study is based on molecular pathways which might predict response to targeted therapies. DNA from 420 patients from the phase III TEAM pathology cohort were used. Patients with a distant recurrence within 5 years were matched by clinical variables to those disease-free at follow up. Copy number analysis was performed using the Affymetrix Oncoscan Assay. Targeted sequencing was performed in a subset of samples for genes based on signaling cassettes mined from the ICGC. Pathways were identified as aberrant if there were copy number variations (CNVs) and/or mutations in any of the pre-determined pathway genes: 1) CCND1/CCND2/CCND3/CDK4/CDK6; 2) FGFR1/FGFR2/FGFR2/FGFR4; and 3) AKT1/AKT2/PIK3CA/PTEN. Kaplan-Meier and log-rank analyses were used for DFS between groups. Hazard ratios were calculated using the Cox proportional hazard models adjusted for age, tumour size, grade, lymph node and HER2 status. Results: 390/420 samples passed informatics QC filters. For the CCND/CDK pathway, patients with no CNV changes experienced a better DFS (HR = 1.7, 95% CI 1.3-2.3, p < 0.001). For the FGFR/FGF pathway, a similar outcome is seen among patients without CNVs (HR = 1.5, 95% CI 1.1-2.0; p = 0.005). For AKT/PIK3CA, a decrease in DFS was seen in those with aberrations (HR = 1.4, 95% CI 1.0-1.8, p = 0.03). Conclusions: We demonstrated that CNVs of genes within CDK4/CCND, PIK3CA/AKT and FGFR pathways are independently linked to high risk of relapse following endocrine treatment, with implications for identifying those patients who are at high-risk for recurrence despite optimal anti-endocrine therapy and linking molecular features driving these cancers to targeted therapies.

Autocrine signaling based selection of combinatorial antibodies that transdifferentiate human stem cells

We report here the generation of antibody agonists from intracellular combinatorial libraries that transdifferentiate human stem cells. Antibodies that are agonists for the granulocyte colony stimulating factor receptor were selected from intracellular libraries on the basis of their ability to activate signaling pathways in reporter cells. We used a specialized "near neighbor" approach in which the entire antibody library and its target receptor are cointegrated into the plasma membranes of a population of reporter cells. This format favors unusual interactions between receptors and their protein ligands and ensures that the antibody acts in an autocrine manner on the cells that produce it. Unlike the natural granulocyte-colony stimulating factor that activates cells to differentiate along a predetermined pathway, the isolated agonist antibodies transdifferentiated human myeloid lineage CD34+ bone marrow cells into neural progenitors. This transdifferentiation by agonist antibodies is different from more commonly used methods because initiation is agenetic. Antibodies that act at the plasma membrane may have therapeutic potential as agents that transdifferentiate autologous cells.

Another look at the life of a neutrophil

Neutrophils are considered as the privates of the innate immune system. They are born in the bone marrow, migrate to the tissues where they kill putative intruders. After their job they are quickly removed from the battlefield by macrophages. This view of a predetermined pathway fitted nicely in their short lifespan of 5 h. However, recent studies indicated that their lifespan was in the order of several days. Recently, it became clear that neutrophils have functions beyond killing of pathogens. The reported half-life of 5 h is hardly compatible with those functions. Moreover, the organism actively invests in rescuing primed neutrophils from clearance by the body. It appears that their half-life is highly dependent on the method used to measure their life span. Here, we discuss the literature and show that neutrophils compartmentalize which could explain partially the differences reported for their lifespan. Moreover, the methodology to label neutrophils ex-vivo could have similar deteriorating effects on their lifespan as found for transfused red blood cells.

R-F1.1 Proximal humeral fractures: Discrepancies between a predetermined clinical pathway and the actual clinical decision

R-F1.1 Proximal humeral fractures: Discrepancies between a predetermined clinical pathway and the actual clinical decision

Protein folding: Independent unrelated pathways or predetermined pathway with optional errors

The observation of heterogeneous protein folding kinetics has been widely interpreted in terms of multiple independent unrelated pathways (IUP model), both experimentally and in theoretical calculations. However, direct structural information on folding intermediates and their properties now indicates that all of a protein population folds through essentially the same stepwise pathway, determined by cooperative native-like foldon units and the way that the foldons fit together in the native protein. It is essential to decide between these fundamentally different folding mechanisms. This article shows, contrary to previous supposition, that the heterogeneous folding kinetics observed for the staphylococcal nuclease protein (SNase) does not require alternative parallel pathways. SNase folding kinetics can be fit equally well by a single predetermined pathway that allows for optional misfolding errors, which are known to occur ubiquitously in protein folding. Structural, kinetic, and thermodynamic information for the folding intermediates and pathways of many proteins is consistent with the predetermined pathway-optional error (PPOE) model but contrary to the properties implied in IUP models.

A unified mechanism for protein folding: predetermined pathways with optional errors.

There is a fundamental conflict between two different views of how proteins fold. Kinetic experiments and theoretical calculations are often interpreted in terms of different population fractions folding through different intermediates in independent unrelated pathways (IUP model). However, detailed structural information indicates that all of the protein population folds through a sequence of intermediates predetermined by the foldon substructure of the target protein and a sequential stabilization principle. These contrary views can be resolved by a predetermined pathway--optional error (PPOE) hypothesis. The hypothesis is that any pathway intermediate can incorporate a chance misfolding error that blocks folding and must be reversed for productive folding to continue. Different fractions of the protein population will then block at different steps, populate different intermediates, and fold at different rates, giving the appearance of multiple unrelated pathways. A test of the hypothesis matches the two models against extensive kinetic folding results for hen lysozyme which have been widely cited in support of independent parallel pathways. The PPOE model succeeds with fewer fitting constants. The fitted PPOE reaction scheme leads to known folding behavior, whereas the IUP properties are contradicted by experiment. The appearance of a conflict with multipath theoretical models seems to be due to their different focus, namely on multitrack microscopic behavior versus cooperative macroscopic behavior. The integration of three well-documented principles in the PPOE model (cooperative foldons, sequential stabilization, optional errors) provides a unifying explanation for how proteins fold and why they fold in that way.

Multilineage Differentiation and Characterization of the Human Fetal Osteoblastic 1.19 Cell Line: A Possible In Vitro Model of Human Mesenchymal Progenitors

The in vitro study of human bone marrow mesenchymal stromal cells (BMMSCs) has largely depended on the use of primary cultures. Although these are excellent model systems, their scarcity, heterogeneity, and limited lifespan restrict their usefulness. This has led researchers to look for other sources of MSCs, and recently, such a population of progenitor/stem cells has been found in mesodermal tissues, including bone. We therefore hypothesized that a well-studied and commercially available clonal human osteoprogenitor cell line, the fetal osteoblastic 1.19 cell line (hFOB), may have multilineage differentiation potential. We found that undifferentiated hFOB cells possess similar cell surface markers as BMMSCs and also express the embryonic stem cell-related pluripotency gene, Oct-4, as well as the neural progenitor marker nestin. hFOB cells can also undergo multilineage differentiation into the mesodermal lineages of chondrogenic and adipocytic cell types in addition to its predetermined pathway, the mature osteoblast. Moreover, as with BMMSCs, under neural-inducing conditions, hFOB cells acquire a neural-like phenotype. This human cell line has been a widely used model of normal osteoblast differentiation. Our data suggest that hFOB cells may provide for researchers an easily available, homogeneous, and consistent in vitro model for study of human mesenchymal progenitor cells.

Walking with Visual Restrictions in Healthy Elderly and Young Adults

ABSTRACTVisual requirements for a simple walking task were evaluated for young and elderly persons to determine if, with normal aging, elderly subjects require more visual information. Ten young adults and 10 elderly people were asked to complete a simple walking task within predetermined pathway boundaries under two conditions of visual restriction. In the reactive condition, subjects automatically received a 200 ms flash of visual information at the halfway point of the walkway. For the predictive condition, subjects did not receive any visual information during the walking trial, but were equipped with an emergency button that would provide 200 ms of visual information whenever they needed it. For both experimental conditions, subjects received additional flashes of visual information if they stepped out of the walkway boundaries. Results showed that older persons stepped out of bounds more often in the reactive condition and gave themselves more visual cues than the younger subjects in the predictive condition. The relative importance of vision during locomotion seems to be higher in the elderly population when compared to young adults.

Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications.

Acute renal failure (ARF) can be defined as a sudden loss of renal function and is a common and serious clinical problem. There are many causes of ARF but the most common cause results from injury to the renal tubular epithelial cells (RTECs). RTECs can be injured by schemia or by cytotoxic agents and, once injured, can die by necrosis or apotosis. In general, necrosis occurs in response to any severe injury, which leads to the biochemical collapse of the cell. Milder forms of the same types of injury cause apoptosis. At the cellular level there are fundamental differences between necrosis and apoptosis. Necrosis results from the additive effect of a number of independent biochemical events that are activated by severe depletion of cell energy stores. By contrast, apoptosis occurs via a coordinated, predictable and pre-determined pathway. These biochemical differences between apoptosis and necrosis have important therapeutic implications. Once a cell has been severely injured, necrosis is difficult to prevent. By contrast, the apoptotic pathway can potentially be modulated to maintain cell viability. The components of the apoptotic pathway that are potentially amenable to therapeutic modulation are discussed in detail in this review.

The Formation of the Duct in Xenopus Involves Recruitment of Posterior Cells by Migrating Pronephric Duct Cells

Cell migration and cell-cell interactions play important roles in numerous processes during embryogenesis. One of these is the formation of the pronephric (Wolffian) duct (PD), which connects the pronephros to the cloaca. It is currently accepted that in most amphibians the pronephric duct is formed by active migration of the pronephric duct rudiment (PDR) cells along a predetermined pathway. However, there is evidence that in Xenopus, the PD may be formed entirely by in situ segregation of cells out of the lateral mesoderm. In this study, we show, using PDR ablation and Xenopus laevis-Xenopus borealis chimeras, that PD elongation in Xenopus requires both active cell migration and an induced recruitment of cells from the posterior. We also show that PDR cell migration is limited to only a few stages during development and that this temporal control is due, at least in part, to changes in the competence of the PD pathway to support cell migration.

New Challenges for Animal Science Teaching

We live in exciting times. Challenging opportunities for the scientifically trained animal scientists abound. As educators, we must accept the leadership challenge for designing and presenting viable research and teaching programs having relevance for today's science-oriented student. Industry, business, government, and educational institutions are seeking animal science graduates who have new insights on the scope of animal science as a profession built on a sound educational foundation. Curriculum changes and the development of new courses to strengthen and to enrich the typical animal science curriculum are needed. There is no formula or predetermined pathway for success. We can, though, build from a strong base that reflects the ingenuity and integrity of the great men and women now pursuing professional careers in animal science.