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Life in a Cambodian Orphanage
What is it like to grow up in an orphanage? What do residents themselves have to say about their experiences? Are there ways that orphanages can be designed to meet children's developmental needs and to provide them with necessities they are unable to receive in their home communities? In this book, detailed observations of children's daily life in a Cambodian orphanage are combined with follow-up interviews of the same children after they have grown and left the orphanage. Their thoughtful reflections show that the quality of care children receive is more important for their well-being than the site in which they receive it. Life in a Cambodian Orphanage situates orphanages within the social and political history of Cambodia, and shows that orphanages need not always be considered bleak sites of deprivation and despair. It suggests best practices for caring for vulnerable children regardless of the setting in which they are living.
eBook
The BFG
The BFG--Big Friendly Giant--kidnaps Sophie from her bed in the orphanage and takes her back to Giantland where she becomes involved in a scheme to end the loathsome activities of nine evil giants.
Book
Association of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial
PurposeROR1 and ROR2 are Type 1 tyrosine kinase-like orphan receptors for Wnt5a that are associated with breast cancer progression. Experimental agents targeting ROR1 and ROR2 are in clinical trials. This study evaluated whether expression levels of ROR1 or ROR2 correlated with one another or with clinical outcomes.MethodsWe interrogated the clinical significance of high-level gene expression of ROR1 and/or ROR2 in the annotated transcriptome dataset from 989 patients with high-risk early breast cancer enrolled in one of nine completed/graduated/experimental and control arms in the neoadjuvant I-SPY2 clinical trial (NCT01042379).ResultsHigh ROR1 or high ROR2 was associated with breast cancer subtypes. High ROR1 was more prevalent among hormone receptor-negative and human epidermal growth factor receptor 2-negative (HR-HER2-) tumors and high ROR2 was less prevalent in this subtype. Although not associated with pathologic complete response, high ROR1 or high ROR2 each was associated with event-free survival (EFS) in distinct subtypes. High ROR1 associated with a worse EFS in HR + HER2- patients with high post-treatment residual cancer burden (RCB-II/III) (HR 1.41, 95% CI = 1.11–1.80) but not in patients with minimal post-treatment disease (RCB-0/I) (HR 1.85, 95% CI = 0.74–4.61). High ROR2 associated with an increased risk of relapse in patients with HER2 + disease and RCB-0/I (HR 3.46, 95% CI = 1.33–9.020) but not RCB-II/III (HR 1.07, 95% CI = 0.69–1.64).ConclusionHigh ROR1 or high ROR2 distinctly identified subsets of breast cancer patients with adverse outcomes. Further studies are warranted to determine if high ROR1 or high ROR2 may identify high-risk populations for studies of targeted therapies.
Journal Article
Journey to the river sea
In 1910, orphaned Maia, sent with her governess to live with eccentric relatives in Manaus, Brazil, endures many hardships before fulfilling her dream of exploring the Amazon River.
Hook's DIY in a Hard Father's Workshop
The captain there, I swear, he's in love with a saw tuning in circular to mitre songs of a wounding. Plainer, of course, though she has her appeal, lolling with Safety Pin-Up Girl '95 beside cobweb, sawdust, final letters, knives.
Journal Article
Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis
In a new study, Yasuhiro Kobayashi and his colleagues show that noncanonical Wnt signaling regulates balanced osteoblast-induced osteoclastogenesis during normal physiology and that this pathway is perturbed in pathophysiological states, such as rheumatoid arthritis. These results explain further how osteoblasts cross-talk with preosteoclasts to ensure matched bone resorption with bone formation during skeletal homeostasis in the adult and also suggest a new target to treat arthritis.
The signaling molecule Wnt regulates bone homeostasis through β-catenin–dependent canonical and β-catenin–independent noncanonical pathways. Impairment of canonical Wnt signaling causes bone loss in arthritis and osteoporosis; however, it is unclear how noncanonical Wnt signaling regulates bone resorption. Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor (Ror) proteins. We showed that Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhanced osteoclastogenesis. Osteoblast-lineage cells expressed Wnt5a, whereas osteoclast precursors expressed Ror2. Mice deficient in either
Wnt5a
or
Ror2
, and those with either osteoclast precursor-specific
Ror2
deficiency or osteoblast-lineage cell-specific
Wnt5a
deficiency showed impaired osteoclastogenesis. Wnt5a-Ror2 signals enhanced receptor activator of nuclear factor-κB (RANK) expression in osteoclast precursors by activating JNK and recruiting c-Jun on the promoter of the gene encoding RANK, thereby enhancing RANK ligand (RANKL)-induced osteoclastogenesis. A soluble form of Ror2 acted as a decoy receptor of Wnt5a and abrogated bone destruction in mouse arthritis models. Our results suggest that the Wnt5a-Ror2 pathway is crucial for osteoclastogenesis in physiological and pathological environments and represents a therapeutic target for bone diseases, including arthritis.
Journal Article
Cultural, autobiographical and absent memories of orphanhood : the girls of Nazareth House remember
This book offers an empirically informed understanding of how cultural, autobiographical and absent memories of orphanhood interact and interconnect or come into being in the re-telling of a life story and construction of an identity. The volume investigates how care experienced identities are embedded within personal, social and cultural practices of remembering. The book stems from research carried out into the life (hi)stories of twelve undervalued 'historical witnesses' (Roberts, 2002) of orphanhood: women who grew up in Nazareth House children's home in Belfast, Northern Ireland, during the 1940s, 50s and 60s. Several themes are covered, including histories of care in Northern Ireland, narratives and memories, sociologies of home, and self and identity. The result is an impressive text that works to introduce readers to the complexity of memory for care experienced people and what this means for their life story and identity.
Book
Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries
To review existing regulations and policies utilised by countries to enable patient access to orphan drugs.
A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.
Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.
Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.
Journal Article