| 1. |
- Verma, Malvika, et al.
(author)
-
A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment
- 2019
-
In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:483
-
Journal article (peer-reviewed)abstract
- Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.
|
|
| 2. |
- Abramson, Alex, et al.
(author)
-
A luminal unfolding microneedle injector for oral delivery of macromolecules
- 2019
-
In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:10, s. 1512-
-
Journal article (peer-reviewed)abstract
- Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes(1,2), yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications(3-5). Compared with subcutaneously administered drugs, oral formulations create less patient discomfort(4), show greater chemical stability at high temperatures(6), and do not generate biohazardous needle waste(7). An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract(8). We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake > 10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.
|
|
| 3. |
- Abramson, Alex, et al.
(author)
-
An ingestible self-orienting system for oral delivery of macromolecules
- 2019
-
In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 363:6427, s. 611-
-
Journal article (peer-reviewed)abstract
- Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.
|
|
| 4. |
- Clark, Douglas S., et al.
(author)
-
Klaus Mosbach Tribute
- 2015
-
In: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 112:4, s. 645-647
-
Journal article (other academic/artistic)
|
|
| 5. |
- Dengler, Juergen, et al.
(author)
-
GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
-
In: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
-
Journal article (peer-reviewed)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
|
|
| 6. |
- Holmes, Thomas P., et al.
(author)
-
Fundamental Economic Irreversibilities Influence Policies for Enhancing International Forest Phytosanitary Security
- 2017
-
In: Current Forestry Reports. - Cham : Springer. - 2198-6436. ; 3:3, s. 244-254
-
Journal article (peer-reviewed)abstract
- National and international efforts to manage forest biosecurity create tension between opposing sources of ecological and economic irreversibility. Phytosanitary policies designed to protect national borders from biological invasions incur sunk costs deriving from economic and political irreversibilities that incentivizes wait-and-see decision-making. However, the potential for irreversible ecological and economic damages resulting from failed phytosanitary policies argues for precautionary measures, creating sunk benefits while increasing the risk of over-investment in phytosanitary security. Here, we describe the inherent tension between these sources of irreversibility in economic terms, relate these forces to type I and type II errors, and use this framework to review national and international efforts to protect forests from biological invasions. Available historical evidence suggests that wait-and-see phytosanitary decision-making has dominated the adoption of precautionary measures in most regions and that willingness to under-regulate may sometimes be orders of magnitude greater than willingness to over-regulate. Reducing scientific uncertainty about threats to biosecurity may help mitigate the tendency to under-regulate, and phytosanitary security measures with relatively modest sunk costs could help protect forests as scientific learning advances. A fuller accounting of the costs associated with type II errors, particularly regarding the suite of non-market ecosystem services at risk, would help decision-makers better understand the trade-offs between the sunk costs of policies and long-term economic losses to stakeholders.
|
|
| 7. |
- Kisa, Phyllis, et al.
(author)
-
Unifying Children's Surgery and Anesthesia Stakeholders Across Institutions and Clinical Disciplines : Challenges and Solutions from Uganda
- 2019
-
In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 43:6, s. 1435-1449
-
Journal article (peer-reviewed)abstract
- BackgroundThere is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration.MethodsThe stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area.ResultsThe Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals.ConclusionCollaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.
|
|
| 8. |
- Taylor, Linnéa, et al.
(author)
-
Seeing through the interface : Poly(ε-Caprolactone) surface modification of poly(glycerol-co-sebacic acid) membranes in adult porcine retinal explants
- 2017
-
In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254. ; 11:8, s. 2349-2358
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the adhesion properties and tissue reactions in an in vitro model of nanofabricated membranes emulating the vitreous cortex. Electrospinning was performed for either 5, 10 or 15 min to create various thicknesses of poly(ε-caprolactone) (PCL) fibre mats on a poly(glycerol-co-sebacic acid) (PGS) surface. These were fused with adult porcine retinal explants, with the fibre side facing the inner retina, and cultured for 5 days. Adherence was assessed by macroscopic inspection, and morphological and immunohistochemical analysis was performed using haematoxylin and eosin (H&E) and markers for photoreceptors and Müller glia (recoverin, NeuN, vimentin and GFAP). TUNEL labelling was performed to assess apoptosis. Five minute specimens displayed poor adherence with an overall structure, apoptosis and photoreceptor and ganglion cell morphology comparable to that of the culture controls, whereas 10 min specimens showed improved neuronal survival; 15 min composite explants adhered only at focal points, were thin and showed extensive degenerative damage. The physical composition of nanofibre meshes is important for adhesion to the inner retina and has a significant impact on neuronal and glial survival in vitro. The results bearing on research involving retinal transplantation are discussed.
|
|
| 9. |
- Yang, Yunlong, et al.
(author)
-
The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
- 2016
-
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11385
-
Journal article (peer-reviewed)abstract
- Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain-and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.
|
|
| 10. |
- Zamora, Juan Carlos, et al.
(author)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Journal article (peer-reviewed)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
