Localized JNK signaling regulates organ size during development.

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these findings provide a new mechanism for how the Hedgehog pathway could contribute to tumorigenesis, and, more importantly, provides a new strategy for cancer therapies. Finally, modulation of JNK signaling centers in developing antennae and legs changes their sizes, suggesting a more generalizable role for JNK signaling in developmental organ size control

Exploring the change across a generation: First-year Physics students’ conceptions and study approaches between 2002-2018

It is often not contested that students’ performance in STEM disciplines is declining. As well as the more recent results from standardized testing of younger students, it is not uncommon to hear university STEM professors anecdotally report of the failure of more recent cohorts to live up to the standard of their predecessors. However, it is rare to find studies which address the purported declining standards amongst students entering university STEM studies using the same instruments over an extended time period.  This repeated cross-sectional study examines how students upon entry into university physics studies respond to an established conceptual survey on mechanics as well as two surveys probing epistemological beliefs. A total of 2448 first-year undergraduate students were surveyed at an Australian research-intensive university from 2002 to 2018. Our findings show that students' conceptions of the structure of physics knowledge and their study approaches, remain remarkably stable. In the measures of physics conceptual understanding, students in the later cohorts return significantly higher scores over the study period. We discuss the backdrop in which this study has occurred and argue that these findings offer a unique insight into similarities and differences of a narrow band of student cohorts over more than a decade

Psychosis and Human Rights: Conflicts in Mental Health Policy and Practice

This paper examines conflicts in polices in England and Wales pertaining to the demand for alternative, non-medical crisis support for those experiencing ‘psychosis’. We examine the limitations of current treatment, policy and legislative frameworks in supporting these demands. In particular, we focus on the limitations of prevailing conceptualisations of ‘human rights’, ‘social inclusion’ and ‘recovery’. These concepts, we argue, are embedded within a broader treatment framework which renders medication as mandatory and all other treatment modalities as inherently subsidiary, and a broader policy framework which is complicit with bio-medical orthodoxies of ‘mental illness’ and prioritises treatment compliance and compulsion. Therefore, in order to advance a ‘human rights’ approach to mental health policy, we argue that reigning orthodoxies inherent within policy and practice must be explicitly challenged to open up spaces for the availability of alternatives

Cost effectiveness of a general practice chronic disease management plan for coronary heart disease in Australia

Background. The cost effectiveness of a general practice-based program for managing coronary heart disease (CHD) patients in Australia remains uncertain. We have explored this through an economic model.Methods. A secondary prevention program based on initial clinical assessment and 3 monthly review, optimising of pharmacotherapies and lifestyle modification, supported by a disease registry and financial incentives for quality of care and outcomes achieved was assessed in terms of incremental cost effectiveness ratio (ICER), in Australian dollars per disability adjusted life year (DALY) prevented.Results. Based on 2006 estimates, 263 487 DALYs were attributable to CHD in Australia. The proposed program would add $115 650 000 to the annual national heath expenditure. Using an estimated 15$8081 per DALY prevented. With more conservative estimates of effectiveness and uptake, estimates of up to $38 316 per DALY are observed in sensitivity analysis.Conclusions. Although innovation in CHD management promises improved future patient outcomes, many therapies and strategies proven to reduce morbidity and mortality are available today. A general practice-based program for the optimal application of current therapies is likely to be cost-effective and provide substantial and sustainable benefits to the Australian community.What is known about this topic? Chronic disease management programs are known to provide gains with respect to reductions in death and disability among patients with coronary heart disease. The cost effectiveness of such programs in the Australian context is not known.What does this paper add? This paper suggests that implementing a coronary heart disease program in Australia is highly cost-effective across a broad range of assumptions of uptake and effectiveness.What are the implications for practitioners? These data provide the economic rationale for the implementation of a chronic disease management program with a disease registry and regular review in Australia

Accelerating the Deactivation of \u3cem\u3eSalmonella enterica\u3c/em\u3e Serovar Newport and \u3cem\u3eEscherichia coli\u3c/em\u3e O157:H7 in Dairy Manure by Modifying pH or Temperature

To assess methods for control of disease-causing bacteria in animal manures prior to field application, we manipulated the temperature or adjusted pH of dairy manure to high (3.5 to 5) or low (10 to 12) values with aluminum sulfate or hydrated lime, and inoculated the manure with Salmonella enterica serovar Newport or Escherichia coli O157:H7, then incubated the manure at ambient temperature. At pH 4.2, S. Newport was eliminated within 6 days; however at pH \u3e4.2 S. Newport was suppressed only temporarily and recovered to concentrations near the unamended controls. pH required to eliminate E. coli O157:H7 was 4.5. Both pathogens were killed by pH 11.0. The pathogens were eliminated within 2 weeks when inoculated manure was incubated at 37°C, whereas at 22°C and 4°C, the organisms persisted for much longer periods. S. Newport survived for over 300 days at 4°C, which has implications for manure spreading in colder seasons

Listening to women: experiences of using closed-loop in type 1 diabetes pregnancy

Introduction: Recent high-profile calls have emphasized that women's experiences should be considered in maternity care provisioning. We explored women's experiences of using closed-loop during type 1 diabetes (T1D) pregnancy to inform decision-making about antenatal rollout and guidance and support given to future users. Methods: We interviewed 23 closed-loop participants in the Automated insulin Delivery Among Pregnant women with T1D (AiDAPT) trial after randomization to closed-loop and ∼20 weeks later. Data were analyzed thematically. Results: Women described how closed-loop lessened the physical and mental demands of diabetes management, enabling them to feel more normal and sleep better. By virtue of spending increased time-in-range, women also worried less about risks to their baby and being judged negatively by health care professionals. Most noted that intensive input and support during early pregnancy had been crucial to adjusting to, and developing confidence in, the technology. Women emphasized that attaining pregnancy glucose targets still required ongoing effort from themselves and the health care team. Women described needing education to help them determine when, and how, to intervene and when to allow the closed-loop to operate without interference. All women reported more enjoyable pregnancy experiences as a result of using closed-loop; some also noted being able to remain longer in paid employment. Conclusions: Study findings endorse closed-loop use in T1D pregnancy by highlighting how the technology can facilitate positive pregnancy experiences. To realize fully the benefits of closed-loop, pregnant women would benefit from initial intensive oversight and support together with closed-loop specific education and training. Clinical Trial Registration number: NCT04938557

Apparently synonymous substitutions in FGFR2affect splicing and result in mild Crouzon syndrome

BACKGROUND: Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2. CASE PRESENTATION: Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis. CONCLUSIONS: These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations

Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome

Background: Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2.Case presentation: Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis.Conclusions: These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations

Individualised, flexible postnatal care: a feasibility study for a randomised controlled trial

AbstractBackground:Postnatal care in hospital is often provided using defined care pathways, with limited opportunity for more refined and individualised care. We explored whether a tertiary maternity service could provide flexible, individualised early postnatal care for women in a dynamic and timely manner, and if this approach was acceptable to women.Methods: A feasibility study was designed to inform a future randomised controlled trial to evaluate an alternative approach to postnatal care. English-speaking women at low risk of medical complications were recruited around 26 weeks gestation to explore their willingness to participate in a study of a new, flexible model of care that involved antenatal planning for early postpartum discharge with additional home-based postnatal care. The earlier women were discharged from hospital, the more home-based visits they were eligible to receive. Program uptake was measured, women&rsquo;s views obtained by a postal survey sent at eight weeks postpartum and clinical data collected from medical records.Results: Study uptake was 39% (109/277 approached). Most women (n=103) completed a postnatal care plan during pregnancy; 17% planned to leave hospital within 12 hours of giving birth and 36% planned to stay 48 hours. At eight weeks postpartum most women (90%) were positive about the concept and 88% would opt for the same program again. Of the 28% who stayed in hospital for the length they had planned, less than half (43%) received the appropriate number of home visits, and only 41% were given an option for the timing of the visit. Most (62%) stayed in hospital longer than planned (probably due to clinical complications); 11% stayed shorter than planned.Conclusions: Women were very positive about individualised postnatal care planning that commenced during pregnancy. Given the hospital stay may be impacted by clinical factors, individualised care planning needs to continue into the postnatal period to take into account circumstances which cannot be planned for during pregnancy. However, individualised care planning during the postnatal period which incorporates a high level of flexibility may be challenging for organisations to manage and implement, and a randomised controlled trial of such an approach may not be feasible.<br /