bluuebunny/crossref_metadata_2025 huggingface dataset:
Time to wait: a systematic review of strategies that affect out-patient waiting times
Authors: Naiker Ugenthiri , FitzGerald Gerry , Dulhunty Joel M. , Rosemann Michael
Published: March 2017

Objective
Out-patient waiting times pose a significant challenge for public patients in need of specialist evaluation and intervention. The aim of the present study was to identify and categorise effective strategies to reduce waiting times for specialist out-patient services with a focus on the Australian healthcare system.

Methods
A systematic review of major health databases was conducted using the key terms ‘outpatient*’ AND ‘waiting time’, ‘process*’ AND ‘improvement in outpatient clinics’. Identified articles were assessed for their relevance by sequential review of the title, abstract and full text. References of the selected manuscripts were scanned for additional relevant articles. Selected articles were evaluated for consistent and emerging themes.

Results
In all, 152 articles were screened, of which 38 were included in the present review. Numerous strategies identified in the articles were consolidated into 26 consistent approaches. Three overarching themes were identified as significantly affecting waiting times: resource realignment, operational efficiency and process improvement.

Conclusions
Strategies to align resources, increase operational efficiency and improve processes provide a comprehensive approach that may reduce out-patient waiting times.

What is known about the topic?
Out-patient waiting times are a challenge in most countries that seek to provide universal access to health care for all citizens. Although there has been extensive research in this area, many patients still experience extensive delays accessing specialist care, particularly in the public health sector. The multiple factors that contribute to bottlenecks and inefficiencies in the referral process and affect patient waiting times are often poorly understood.

What does this paper add?
This paper reviews the published healthcare literature to identify strategies that affect specialist out-patient waiting times for patients. The findings suggest that there are numerous operational strategies that affect waiting times. These strategies may be categorised into three overarching themes (resource alignment, operational efficiencies and out-patient processes) that, when actioned in a coordinated approach, have the potential to significantly reduce out-patient waiting times.

What are the implications for practitioners?
This paper identifies evidence-based strategies for aligning resources, improving operational efficiency and streamlining processes, which may provide improvements to specialist out-patient waiting times for patients. Addressing the identified organisational, person-related, cultural and attitudinal factors will assist health system managers and health practitioners target the most appropriate improvement activities to reduce waiting times.
Plants in constrained canopy micro-swards compensate for decreased root biomass and soil exploration with increased amounts of rhizosphere carboxylates
Authors: Jeffery Robert P. , Simpson Richard J. , Lambers Hans , Kidd Daniel R. , Ryan Megan H.
Published: March 2017

Root traits related to phosphorus (P) acquisition are used to make inferences about a species’ P-foraging ability under glasshouse conditions. However, the effect on such root traits of constrained canopy spread, as occurs in dense pasture swards, is unknown. We grew micro-swards of Trifolium subterraneum L. and Ornithopus compressus L. at 15 and 60 mg kg–1 soil P in a glasshouse. Shoots either spread beyond the pot perimeter or were constrained by a cylindrical sleeve adjusted to canopy height. After 8 weeks, shoot and root dry mass (DM), shoot tissue P concentration, rhizosphere carboxylates, arbuscular mycorrhizal (AM) fungal colonisation, total and specific root length (TRL and SRL respectively), average root diameter (ARD) and average root hair length (ARHL) were measured. In all species and treatments, constrained canopy spread decreased root DM (39–59%), TRL (27–45%) and shoot DM (10–28%), and increased SRL (20–33%), but did not affect ARD, ARHL and AM fungal colonisation. However, shoot P concentration and content increased, and rhizosphere carboxylates increased 3.5 to 12-fold per unit RL and 2.0- to 6.5-fold per micro-sward. Greater amounts of rhizosphere carboxylates when canopy spread was constrained appeared to compensate for reduced root growth enabling shoot P content to be maintained.
Deltex2 represses MyoD expression and inhibits myogenic differentiation by acting as a negative regulator of Jmjd1c
Authors: Luo Dan , de Morree Antoine , Boutet Stephane , Quach Navaline , Natu Vanita , Rustagi Arjun , Rando Thomas A.
Published: March 2017

Significance

The data presented address a fundamental mechanism controlling the expression of a master regulator of cellular differentiation, MyoD, by a member of the Deltex family of proteins. We show that MyoD expression is regulated by modulation of histone methylation in its promoter region by the histone demethylase, Jjmd1c. These data provide insight into the epigenetic control of gene expression in the regulation of myogenic differentiation.
Model of brain activation predicts the neural collective influence map of the brain
Authors: Morone Flaviano , Roth Kevin , Min Byungjoon , Stanley H. Eugene , Makse Hernán A.
Published: March 2017

Significance

Evidence suggests that the brain is arranged in functionally specialized modules to form a network of networks (NoN). Understanding how functionality emerges from the integration of such modular architectures is one of the greatest scientific challenges. We introduce a model of brain NoN, which is robust against random node failures, captures the integration of functionally specialized modules in the brain, and provides falsifiable predictions about the locations of the most influential nodes, called neural collective influencers, in the brain network—predictions that are impossible in existing but fragile models of interdependent NoN. If confirmed by experiment, our results may pave the way for applications of clinical interest.
After the mines: the changing social and economic landscape of Malawi–South Africa migration
Authors: Johnson Jessica A.
Published: March 2017

By the early 1970s, Malawi was the most significant supplier of mine labour to South Africa. Since then, for a variety of reasons, mine migrancy has dwindled. Nevertheless, migration to South Africa today looms large in the popular imagination, and is pursued by substantial numbers of Malawians, particularly men. By comparison with earlier migrants, however, their trajectories are less certain, their strategies more piecemeal. This paper will focus on contemporary migration to South Africa by young men from a particular village in Chiradzulu District, southern Malawi. Emphasising perspectives from their home village, it will offer insight into the impact of their migration upon family and gender relations, the social and economic situations of the wives and matrilineal kin whom they leave behind, and the tangible and intangible impacts of aspirations to South African migration.
Weighted Rellich type inequalities related to Baouendi-Grushin operators
Authors: Kombe Ismail , Yener Abdullah
Published: March 2017

We find a simple sufficient criterion on a pair of nonnegative weight functions

a

(
x
,
y
)

a\left ( x,y\right )

and

b

(
x
,
y
)

b\left ( x,y\right )

in

R

m
+
k

\mathbb {R} ^{m+k}

so that the general weighted

L

p

L^{p}

Rellich type inequality
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="integral Underscript double-struck upper R Superscript m plus k Baseline Endscripts a left-parenthesis x comma y right-parenthesis StartAbsoluteValue normal upper Delta Subscript gamma Baseline u left-parenthesis x comma y right-parenthesis EndAbsoluteValue Superscript p Baseline d x d y greater-than-or-equal-to integral Underscript double-struck upper R Superscript m plus k Baseline Endscripts b left-parenthesis x comma y right-parenthesis StartAbsoluteValue u left-parenthesis x comma y right-parenthesis EndAbsoluteValue Superscript p Baseline d x d y">

∫

R

m
+
k

a

(
x
,
y
)

|

Δ

γ

u

(
x
,
y
)

|

p

d
x
d
y
≥

∫

R

m
+
k

b

(
x
,
y
)

|
u

(
x
,
y
)

|

p

d
x
d
y

\begin{equation*} \int _{\mathbb {\mathbb {R}}^{m+k}}a\left ( x,y\right ) \left \vert \Delta _{\gamma }u\left ( x,y\right ) \right \vert ^{p}dxdy\geq \int _{\mathbb {\mathbb {R}}^{m+k}}b\left ( x,y\right ) \left \vert u\left ( x,y\right ) \right \vert ^{p}dxdy \end{equation*}

holds for all

u
∈

C

0

∞

(

R

m
+
k

)

u\in C_{0}^{\infty }(\mathbb {R}^{m+k})

. Here

Δ

γ

=

Δ

x

+

|

x

|

2
γ

Δ

y

\Delta _{\gamma }=\Delta _{x}+|x|^{2\gamma }\Delta _{y}

is the Baouendi-Grushin operator,

γ
>
0
,

\gamma >0,

m
,
k
≥
1

m,k\geq 1

and

p
>
1

p>1

. It is important to point out here that our approach is constructive in the sense that it allows us to retrieve already established weighted sharp Rellich type inequalities as well as to get other new results with an explicit constant on

R

m
+
k

.

\mathbb {\mathbb {R}}^{m+k}.

We also obtain a sharp

L

p

L^{p}

Rellich type inequality that connects first to second order derivatives and several new two-weight Rellich type inequalities with remainder terms on smooth bounded domains

Ω
\Omega

in

R

m
+
k

\mathbb {\mathbb {R}}^{m+k}

via a nonlinear differential inequality.
Discreteness of 𝐹-jumping numbers at isolated non-ℚ-Gorenstein points
Authors: Graf Patrick , Schwede Karl
Published: March 2017

We show that the

F
F

-jumping numbers of a pair

(
X
,

a

)

(X, \mathfrak {a})

in positive characteristic have no limit points whenever the symbolic Rees algebra of

−

K
X

-K_X

is finitely generated outside an isolated collection of points. We also give a characteristic zero version of this result, as well as a generalization of the Hartshorne–Speiser–Lyubeznik–Gabber stabilization theorem describing the non-

F
F

-pure locus of a variety.
PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in Xenopus and mammalian cells
Authors: Edens Lisa J. , Dilsaver Matthew R. , Levy Daniel L.
Published: March 2017

How nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. We previously reported that conventional protein kinase C (cPKC) contributes to nuclear size reductions that occur during early Xenopus development. Here we report that PKC-mediated phosphorylation of lamin B3 (LB3) contributes to this mechanism of nuclear size regulation. By mapping PKC phosphorylation sites on LB3 and testing the effects of phosphomutants in Xenopus laevis embryos, we identify the novel site S267 as being an important determinant of nuclear size. Furthermore, FRAP studies demonstrate that phosphorylation at this site increases lamina dynamics, providing a mechanistic explanation for how PKC activity influences nuclear size. We subsequently map this X. laevis LB3 phosphorylation site to a conserved site in mammalian lamin A (LA), S268. Manipulating PKC activity in cultured mammalian cells alters nuclear size, as does expression of LA-S268 phosphomutants. Taken together, these data demonstrate that PKC-mediated lamin phosphorylation is a conserved mechanism of nuclear size regulation.
DeepEM3D: approaching human-level performance on 3D anisotropic EM image segmentation
Authors: Zeng Tao , Wu Bian , Ji Shuiwang
Published: March 2017

Motivation

Progress in 3D electron microscopy (EM) imaging has greatly facilitated neuroscience research in high-throughput data acquisition. Correspondingly, high-throughput automated image analysis methods are necessary to work on par with the speed of data being produced. One such example is the need for automated EM image segmentation for neurite reconstruction. However, the efficiency and reliability of current methods are still lagging far behind human performance.

Results

Here, we propose DeepEM3D, a deep learning method for segmenting 3D anisotropic brain electron microscopy images. In this method, the deep learning model can efficiently build feature representation and incorporate sufficient multi-scale contextual information. We propose employing a combination of novel boundary map generation methods with optimized model ensembles to address the inherent challenges of segmenting anisotropic images. We evaluated our method by participating in the 3D segmentation of neurites in EM images (SNEMI3D) challenge. Our submission is ranked #1 on the current leaderboard as of Oct 15, 2016. More importantly, our result was very close to human-level performance in terms of the challenge evaluation metric: namely, a Rand error of 0.06015 versus the human value of 0.05998.

Availability and Implementation

The code is available at https://github.com/divelab/deepem3d/

Supplementary information

Supplementary data are available at Bioinformatics online.
An unusual case of right upper quadrant pain in a pregnant woman
Authors: Modayil Veena , Nelson Mathew , Stankard Brendon
Published: March 2017

Uterine fibroids occur in up to 30% of women of reproductive age and can cause complications during pregnancy that can harm mother and fetus, such as prematurity and increased risk of miscarriage. This article describes a pregnant woman whose abdominal pain was diagnosed as degenerating uterine fibroids.
New Jersey PA regulation and the march on Trenton
Authors: Ramos Maryann , Mandel Ellen
Published: March 2017

New Jersey was the next to the last state to recognize physician assistants (PAs) and pass legislation allowing them to practice. This first-person account supported by interviews with those who were there details the trail to NJ licensure, including the development of a state society, the growth of support from strong leaders in the medical and academic communities, and the grassroots efforts of many PAs aspiring to work in their home state.
Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache
Authors: Janis Jeffrey E. , Barker Jenny C. , Palettas Marilly
Published: March 2017

Background:

Onabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve–directed BOTOX injection as an independent long-term therapeutic option has not been investigated.

Methods:

The technique for peripheral nerve–directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked.

Results:

Initial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, P < 0.006), headache days/mo (9.2 ± 12.7, P < 0.0009), and migraine severity (2.6 ± 2.5, P < 0.00008) versus baseline. MHI improved from the initiation of diagnostic injections to the establishment of steady-state injections (P < 0.002), and further improved over time (P < 0.05, mean follow-up 615 days) with no desensitization observed. Decompressive surgery resulted in significant improvement in MHI (100.8 ± 109.7, P < 0.0000005), headache days/mo (10.8 ± 12.7, P < 0.000002), migraine severity (3.0 ± 3.8, P < 0.00001), and migraine duration in hours (16.8 ± 21.6, P < 0.0007). MHI improvement with surgery was better than long-term BOTOX injections (P < 0.05).

Conclusions:

Though inferior to surgical decompression, preliminary data demonstrate that targeted peripheral nerve–directed BOTOX injection is an effective primary therapy for MH representing a possible alternative to nondirected BOTOX injection with decreased dosage requirements and potentially decreased cost.
The Effect of Soft Tissue Infections on Device Performance in Adult Cochlear Implant Recipients
Authors: McAllister Kerrie , Linkhorn Hannah , Gruber Mayaan , Giles Ellen , Neeff Michel
Published: March 2017

Objective:

The aim of this study was to examine the effect of cochlear implant (CI) site infection and its subsequent management on CI mapping and CI performance. Risk factors for CI infections and pathogens causing infections were reviewed. Treatment options for CI infections were examined.

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Adult patients with a significant CI soft tissue infection from the Northern Cochlear Implant Programme, New Zealand over a 10-year period (August 2004 until August 2014).

Intervention:

Patients were treated with intravenous antibiotics, washout and debridement or ex-plantation and reimplantation of CI.

Main Outcome Measure:

CI mapping results and implant performance before and after management of CI infections were compared.

Results:

There were nine CI infections. Most patients (7/9) were treated with washout and debridement. One patient required removal of the CI and one patient was deemed medically unfit for a general anaesthetic and was managed conservatively with antibiotics alone. Seven patients received long-term antibiotics. Four patients were able to maintain CI performance after salvage treatment of the CI infection. Three patients had poorer CI performance after salvage treatment. One patient had reimplantation and became a nonuser due to only partial reinsertion.

Conclusion:

The pathophysiology of CI infections is complex. Infections can occur many years after CI surgery. The most common bacteria identified were Staphylococcus aureus, Pseudomonas aeruginosa, and skin commensals. Biofilms are present around implants that are removed from patients and biofilms may play a role in CI infections, but the mechanism of infection is not clear.
The Relationship of Superficial Cutaneous Nerves and Interperforator Connections in the Leg: A Cadaveric Anatomical Study
Authors: Gascoigne Adam C. , Ian Taylor G. , Corlett Russell J. , Briggs Chris , Ashton Mark W.
Published: March 2017

Background:

The lower limb is a source of many flaps both for closure of local defects and for free transfer. Fasciocutaneous flap techniques have been progressively refined, although the vascular basis for their success needs clarification.

Methods:

Archival studies of 48 lower limbs were reviewed and combined with 20 studies of lower limbs from fresh cadavers, making a total of 68 investigations. Lower limbs were injected with a dilute lead oxide solution; the integument was removed and radiographed; and the cutaneous nerves were dissected, tagged with wire, radiographed again, and their paths traced on the original images.

Results:

The major cutaneous nerves in the leg are paralleled by a longitudinal vascular axis often comprising long branches with large-caliber true anastomotic connections between perforators. The most highly developed vascular axes followed the medial sural cutaneous and saphenous nerves, together with their accompanying veins, immediately superficial to the deep fascia. The intervening areas were characterized by shorter branches usually connected by small-caliber choke anastomotic connections.

Conclusions:

These findings provide the anatomical basis for the observed reliability of longitudinal flaps in the leg. The superficial cutaneous nerves of the leg, especially the saphenous and medial sural cutaneous nerves, are paralleled by a vascular axis on or beside the nerve comprising long perforator branches connected usually but not always by large-caliber true anastomotic connections. This emphasizes the importance of understanding the characteristics of interperforator anastomoses when designing and raising flaps.
Role of Mitomycin C in Preventing Capsular Contracture in Implant-Based Reconstructive Breast Surgery: A Randomized Controlled Trial
Authors: Nava Maurizio Bruno , Rocco Nicola , Catanuto Giuseppe , Frangou Joanna , Rispoli Corrado , Ottolenghi Joseph , Bruno Novella , Spano Andrea
Published: March 2017

Background:

Capsular contracture represents the most frequent complication after implant-based breast reconstruction. An experimental study on mice demonstrated that capsule formation around breast implants is considerably diminished after topical application of mitomycin C. The authors conducted a randomized controlled clinical trial investigating the efficacy of mitomycin C in reducing capsular contracture rates following implant-based breast reconstruction after mastectomy for breast cancer.

Methods:

The authors randomized all women older than 18 years scheduled for the second stage of an implant-based breast reconstruction after mastectomy for breast cancer at the National Cancer Institute in Milan from October of 2005 to February of 2010 to receive or not receive the topical application of mitomycin C during surgery. The authors assessed capsular contracture, major postoperative complications, and aesthetic outcome.

Results:

The authors randomized 322 patients to receive mitomycin C or not at the second stage of implant-based breast reconstruction. One hundred sixty-two patients were allocated to the mitomycin C group and 160 patients were allocated to the control group. The relative risk of capsular contracture in the mitomycin C group was 0.92 (95 percent CI, 0.60 to 1.41). Major complications leading to reintervention, oncologic outcomes, and aesthetic outcomes were comparable between the two groups.

Conclusions:

This is the first trial reporting data about the use of mitomycin C in breast reconstructive surgery in a clinical setting. Mitomycin C seems not to significantly affect capsular contracture rate and severity following implant-based reconstructive breast surgery at the tested doses.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Insight into the Pathophysiologic Mechanisms behind Cognitive Dysfunction in Trigonocephaly
Authors: van der Vlugt Joris J. B. , van der Meulen Jacques J. M. N. , van den Braak Robert R. J. Coebergh , Vermeij-Keers Christl , Horstman Edwin G. C. , Hovius Steven E. R. , Verhulst Frank C. , Wierdsma André I. , Lequin Maarten H. , Okkerse Jolanda M. E.
Published: March 2017

Background:

The relationship between trigonocephaly and cognitive problems might be explained by: secondary mechanical factors related to growth restriction of the skull, and primary structural defects caused by a shared mechanism related to brain developmental disorder(s) and skull malformation. However, because the exact pathophysiology remains unknown, we examined the pathophysiologic mechanisms behind cognitive dysfunction in patients with trigonocephaly, with an aim of providing a model for cognitive dysfunction based on routinely available variables.

Methods:

Included were 72 patients with trigonocephaly who were operated on. Postoperatively, intelligence was assessed prospectively. The two independent variables, secondary mechanical and primary brain developmental mechanisms, were evaluated retrospectively. Computed tomographic imaging was used to assess skull volume and severity of the frontal stenosis (secondary mechanical factors), width of the central part of the lateral ventricles, and other structural brain anomalies (primary brain developmental factors). Extracranial congenital anomalies were also taken into account.

Results:

No association was found between secondary mechanical factors and postoperative IQ score. Width of the central part of the lateral ventricles, and an interaction effect between this width and additional extracranial anomalies, showed a significant negative association with postoperative IQ.

Conclusions:

Primary brain developmental disorders seem to play an important role in the development of cognitive problems in trigonocephaly. Assessment of width of the central part of the lateral ventricle scores and additional extracranial congenital anomalies for the early prediction of cognitive problems in patients with trigonocephaly could be clinically valuable and can be performed using routinely available tools.
First Female-to-Male Facial Confirmation Surgery with Description of a New Procedure for Masculinization of the Thyroid Cartilage (Adam’s Apple)
Authors: Deschamps-Braly Jordan C. , Sacher Caitlin L. , Fick Jennifer , Ousterhout Douglas K.
Published: March 2017

Although male-to-female transgender patients commonly seek facial feminization surgery, facial masculinization surgery in the female-to-male transgender population is unreported in the literature. This report documents the first known female-to-male facial masculinization surgery, including a new technique for creating an “Adam’s apple” to enhance the facial masculine appearance of a natal female. The authors “reversed” the methods typically used to feminize male facial features, and modified the forehead, nose, and chin to masculinize the patient’s natal female facial features. The authors devised a novel technique to augment the thyroid cartilage using autologous rib cartilage to create a visible Adam’s apple. Initially, masculinization of the chin was accomplished with a multisegment chin osteotomy with grafts to vertically expand and widen the chin along with correcting pronounced microgenia. Subsequently, a second facial masculinization procedure was performed to masculinize the forehead, nose, and thyroid cartilage. Rib cartilage was harvested and carved into an appropriately shaped thyroid cartilage onlay graft and then attached and integrated with the native thyroid cartilage, creating a fully mobile cartilage that translocates up and down with swallowing and a visible Adam’s apple. Previously described techniques to masculinize the facial features of natal male patients were adapted to masculinize the female-to-male patient. Those procedures were combined with the novel technique to create a visually perceptible and naturally mobile Adam’s apple in the female-to-male transsexual patient. Collectively, these described procedures can now provide most female-to-male transsexual patients with a satisfying transformation of their facial features.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation
Authors: Shammas Ronnie L. , Fales Andrew M. , Crawford Bridget M. , Wisdom Amy J. , Devi Gayathri R. , Brown David A. , Vo-Dinh Tuan , Hollenbeck Scott T.
Published: March 2017

Background:

Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics.

Methods:

To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar–labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells.

Results:

Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar–labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models.

Conclusions:

Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar–labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.
Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model
Authors: Giatsidis Giorgio , Cheng Liying , Facchin Federico , Haddad Anthony , Lujan-Hernandez Jorge , Lancerotto Luca , Nabzdyk Christoph Gunther , Matsumine Hajime , Orgill Dennis P.
Published: March 2017

Background:

Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential.

Methods:

Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis.

Results:

Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at −25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes.

Conclusion:

Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.
Acellular Hypothermic Extracorporeal Perfusion Extends Allowable Ischemia Time in a Porcine Whole Limb Replantation Model
Authors: Kueckelhaus Maximilian , Dermietzel Alexander , Alhefzi Muayyad , Aycart Mario A. , Fischer Sebastian , Krezdorn Nicco , Wo Luccie , Maarouf Omar H. , Riella Leonardo V. , Abdi Reza , Bueno Ericka M. , Pomahac Bohdan
Published: March 2017

Background:

One of the major challenges in traumatic amputation is the need to keep ischemia time brief (4 to 6 hours) to avoid ischemic damage and enable successful replantation. The current inability to meet this challenge often leads to traumatic limb loss, which has a considerable detrimental impact on the quality of life of patients.

Methods:

The authors’ team built a portable extracorporeal membrane oxygenator device for the perfusion of amputated extremities with oxygenated acellular solution under controlled parameters. The authors amputated forelimbs of Yorkshire pigs, perfused them ex vivo with acellular Perfadex solution for 12 hours at 10°C in their device, and subsequently replanted them into the host animal. The authors used limbs stored on ice slurry for 4 hours before replantation as their control group.

Results:

Clinical observation and histopathologic evaluation both demonstrated that there was less morbidity and less tissue damage to the cells during preservation and after replantation in the perfusion group compared with the standard of care. Significant differences in blood markers of muscle damage and tissue cytokine levels underscored these findings.

Conclusions:

The authors demonstrated the feasibility and superiority of ex vivo hypothermic oxygenated machine perfusion for preservation of amputated limbs over conventional static cold storage and herewith a substantial extension of the allowable ischemia time for replantation after traumatic amputation. This approach could also be applied to the field of transplantation, expanding the potential pool of viable donor vascularized composite allografts.
The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue
Authors: He Yunfan , Dong Ziqing , Xie Gan , Zhou Tao , Lu Feng
Published: March 2017

Background:

Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue.

Method:

In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control.

Results:

In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation.

Conclusions:

Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.
Current Concepts in the Surgical Management of Lymphedema
Authors: Kung Theodore A. , Champaneria Manish C. , Maki Jeffrey H. , Neligan Peter C.
Published: March 2017

Learning Objectives:

After studying this article, the participant should be able to: 1. Discuss the key points in diagnosing lymphedema. 2. Understand the imaging modalities that facilitate diagnosis and surgical planning. 3. Appreciate the indications for both physiologic and ablative procedures. 4. Recognize the potential role of lymphaticovenular anastomosis and vascularized lymph node transfer in the treatment of patients with lymphedema.

Lymphedema is an incurable disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within the soft tissues. Although this condition may result from a primary structural defect of the lymphatic system, most cases in developed countries are secondary to iatrogenic causes. The diagnosis of lymphedema can be made readily by performing a clinical history and physical examination and may be confirmed by imaging studies such as lymphoscintigraphy, magnetic resonance lymphangiography, or indocyanine green lymphangiography. Nonsurgical treatment continues to be the mainstay of lymphedema management. However, advances in microsurgical techniques have revolutionized surgical options for treating lymphedema, and emerging evidence suggests that reconstructive methods may be performed to restore lymphatic flow. Procedures such as lymphaticovenular anastomosis and vascularized lymph node transfer can potentially offer a more permanent solution to chronic lymphedema, and initial studies have demonstrated promising results.
Direct-to-Implant Breast Reconstruction without the Use of an Acellular Dermal Matrix Is Cost Effective and Oncologically Safe
Authors: Serrurier L. Charles. J. , Rayne Sarah , Venter Marisse , Benn Carol-Ann
Published: March 2017

Background:

Direct-to-implant breast reconstruction is a predictable, reliable, and cost-effective reconstruction. Most units performing direct-to-implant reconstructions recommend the use of an acellular dermal matrix or a mesh to reinforce the lower pole of the breast reconstruction.

Methods:

Two hundred seventy-two consecutive patients with 488 immediate direct-to-implant breast reconstructions performed in a 34-month period are included in this group. Mean follow-up of this group is 35 months.

Results:

Four hundred eight reconstructions were performed through a lazy-S mastectomy, and 80 were performed through a Wise pattern mastectomy. Two local recurrences occurred. Minor complications accounted for 5.5 percent (n = 27): seromas, 3.4 percent (n = 17); wound healing problems, 0.6 percent (n = 3); and grade 2 capsular contracture, 1.4 percent (n = 7). Major complications accounted for 4.3 percent (n = 21): infection, 0.8 percent (n = 4); prosthetic loss, 0.4 percent (n = 2); hematoma, 0.4 percent (n = 2); and wounds requiring débridement, 2 percent (n = 10). The additional cost of acellular dermal matrix is dependent on manufacturer and size, but increases the cost of the procedure by 35.5 to 47.7 percent.

Conclusions:

This reconstruction method compares very favorably with published data from other units as far as early and late complications and cosmetic outcome are concerned. It has a complication rate similar to that of reconstructions using an acellular dermal matrix and is more cost effective.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A new low-turbulence wind tunnel for animal and small vehicle flight experiments
Authors: Quinn Daniel B. , Watts Anthony , Nagle Tony , Lentink David
Published: March 2017

Our understanding of animal flight benefits greatly from specialized wind tunnels designed for flying animals. Existing facilities can simulate laminar flow during straight, ascending and descending flight, as well as at different altitudes. However, the atmosphere in which animals fly is even more complex. Flow can be laminar and quiet at high altitudes but highly turbulent near the ground, and gusts can rapidly change wind speed. To study flight in both laminar and turbulent environments, a multi-purpose wind tunnel for studying animal and small vehicle flight was built at Stanford University. The tunnel is closed-circuit and can produce airspeeds up to 50 m s−1in a rectangular test section that is 1.0 m wide, 0.82 m tall and 1.73 m long. Seamless honeycomb and screens in the airline together with a carefully designed contraction reduce centreline turbulence intensities to less than or equal to 0.030% at all operating speeds. A large diameter fan and specialized acoustic treatment allow the tunnel to operate at low noise levels of 76.4 dB at 20 m s−1. To simulate high turbulence, an active turbulence grid can increase turbulence intensities up to 45%. Finally, an open jet configuration enables stereo high-speed fluoroscopy for studying musculoskeletal control in turbulent flow.
Accuracy of climate-based forecasts of pathogen spread
Authors: Schatz Annakate M. , Kramer Andrew M. , Drake John M.
Published: March 2017

Species distribution models (SDMs) are a tool for predicting the eventual geographical range of an emerging pathogen. Most SDMs, however, rely on an assumption of equilibrium with the environment, which an emerging pathogen, by definition, has not reached. To determine if some SDM approaches work better than others for modelling the spread of emerging, non-equilibrium pathogens, we studied time-sensitive predictive performance of SDMs forBatrachochytrium dendrobatidis, a devastating infectious fungus of amphibians, using multiple methods trained on time-incremented subsets of the available data. We split our data into timeline-based training and testing sets, and evaluated models on each set using standard performance criteria, including AUC, kappa, false negative rate and the Boyce index. Of eight models examined, we found that boosted regression trees and random forests performed best, closely followed by MaxEnt. As expected, predictive performance generally improved with the length of time series used for model training. These results provide information on how quickly the potential extent of an emerging disease may be determined, and identify which modelling frameworks are likely to provide useful information during the early phases of pathogen expansion.
Drosophilaenhancer-Gal4 lines show ectopic expression during development
Authors: Casas-Tintó Sergio , Arnés Mercedes , Ferrús Alberto
Published: March 2017

InDrosophila melanogasterthe most widely used technique to drive gene expression is the binary UAS/Gal4 system. We show here that a set of nervous system specific enhancers (elav, D42/Toll-6, OK6/RapGAP1) display ectopic activity in epithelial tissues during development, which is seldom considered in experimental studies. This ectopic activity is variable, unstable and influenced by the primary sequence of the enhancer and the insertion site in the chromosome. In addition, the ectopic activity is independent of the protein expressed, Gal4, as it is reproduced also with the expression of Gal80. Another enhancer, LN2 from thesex lethal(Sxl) gene, shows sex-dependent features in its ectopic expression. Feminization of LN2 expressing males does not alter the male specific pattern indicating that the sexual dimorphism of LN2 expression is an intrinsic feature of this enhancer. Other X chromosome enhancers corresponding to genes not related to sex determination do not show sexual dimorphism in their ectopic expressions. Although variable and unstable, the ectopic activation of enhancer-Gal4 lines seems to be regulated in terms of tissue and intensity. To characterize the full domain of expression of enhancer-Gal4 constructs is relevant for the design of transgenic animal models and biotechnology tools, as well as for the correct interpretation of developmental and behavioural studies in which Gal4 lines are used.
Propagation of combustion waves in the shell–core energetic materials with external heat losses
Authors: Gubernov V. V. , Kudryumov V. N. , Kolobov A. V. , Polezhaev A. A.
Published: March 2017

In this paper, the properties and stability of combustion waves propagating in the composite solid energetic material of the shell–core type are numerically investigated within the one-dimensional diffusive-thermal model with heat losses to the surroundings. The flame speed is calculated as a function of the parameters of the model. The boundaries of stability are determined in the space of parameters by solving the linear stability problem and direct integration of the governing non-stationary equations. The results are compared with the characteristics of the combustion waves in pure solid fuel. It is demonstrated that a stable travelling combustion wave solution can exist for the parameters of the model for which the flame front propagation is unstable in pure solid fuel and it can propagate several times faster even in the presence of significant heat losses.
Terrestrial reproduction as an adaptation to steep terrain in African toads
Authors: Liedtke H. Christoph , Müller Hendrik , Hafner Julian , Penner Johannes , Gower David J. , Mazuch Tomáš , Rödel Mark-Oliver , Loader Simon P.
Published: March 2017

How evolutionary novelties evolve is a major question in evolutionary biology. It is widely accepted that changes in environmental conditions shift the position of selective optima, and advancements in phylogenetic comparative approaches allow the rigorous testing of such correlated transitions. A longstanding question in vertebrate biology has been the evolution of terrestrial life histories in amphibians and here, by investigating African bufonids, we test whether terrestrial modes of reproduction have evolved as adaptations to particular abiotic habitat parameters. We reconstruct and date the most complete species-level molecular phylogeny and estimate ancestral states for reproductive modes. By correlating continuous habitat measurements from remote sensing data and locality records with life-history transitions, we discover that terrestrial modes of reproduction, including viviparity evolved multiple times in this group, most often directly from fully aquatic modes. Terrestrial modes of reproduction are strongly correlated with steep terrain and low availability of accumulated water sources. Evolutionary transitions to terrestrial modes of reproduction occurred synchronously with or after transitions in habitat, and we, therefore, interpret terrestrial breeding as an adaptation to these abiotic conditions, rather than an exaptation that facilitated the colonization of montane habitats.
First macrobiota biomineralization was environmentally triggered
Authors: Wood Rachel , Ivantsov Andrey Yu , Zhuravlev Andrey Yu
Published: March 2017

Why large and diverse skeletons first appeared
ca
550 Ma is not well understood. Many Ediacaran skeletal biota show evidence of flexibility, and bear notably thin skeletal walls with simple, non-hierarchical microstructures of either aragonite or high-Mg calcite. We present evidence that the earliest skeletal macrobiota, found only in carbonate rocks, had close soft-bodied counterparts hosted in contemporary clastic rocks. This includes the calcareous discoidal fossil
Suvorovella,
similar to holdfasts of Ediacaran biota taxa previously known only as casts and moulds, as well as tubular and vase-shaped fossils. In sum, these probably represent taxa of diverse affinity including unicellular eukaryotes, total group cnidarians and problematica. Our findings support the assertion that the calcification was an independent and derived feature that appeared in diverse groups where an organic scaffold was the primitive character, which provided the framework for interactions between the extracellular matrix and mineral ions. We conclude that such skeletons may have been acquired with relative ease in the highly saturated, high alkalinity carbonate settings of the Ediacaran, where carbonate polymorph was further controlled by seawater chemistry. The trigger for Ediacaran biomineralization may have been either changing seawater Mg/Ca and/or increasing oxygen levels. By the Early Cambrian, however, biomineralization styles and the range of biominerals had significantly diversified, perhaps as an escalating defensive response to increasing predation pressure. Indeed skeletal hardparts had appeared in clastic settings by Cambrian Stage 1, suggesting independence from ambient seawater chemistry where genetic and molecular mechanisms controlled biomineralization and mineralogy had become evolutionarily constrained.