15 research outputs found
Quality of life in restorative versus non-restorative resections for rectal cancer:systematic review
BACKGROUND: Low rectal cancers could be treated using restorative (anterior resection, AR) or non-restorative procedures with an end/permanent stoma (Hartmannâs, HE; or abdominoperineal excision, APE). Although the surgical choice is determined by tumour and patient factors, quality of life (QoL) will also influence the patient's future beyond cancer. This systematic review of the literature compared postoperative QoL between the restorative and non-restorative techniques using validated measurement tools. METHODS: The review was registered on PROSPERO (CRD42020131492). Embase and MEDLINE, along with grey literature and trials websites, were searched comprehensively for papers published since 2012. Inclusion criteria were original research in an adult population with rectal cancer that reported QoL using a validated tool, including the European Organization for Research and Treatment of Cancer QLQ-CR30, QLQ-CR29, and QLQ-CR38. Studies were included if they compared AR with APE (or HE), independent of study design. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Outcomes of interest were: QoL, pain, gastrointestinal (GI) symptoms (stool frequency, flatulence, diarrhoea and constipation), and body image. RESULTS: Nineteen studies met the inclusion criteria with a total of 6453 patients; all papers were observational and just four included preoperative evaluations. There was no identifiable difference in global QoL and pain between the two surgical techniques. Reported results regarding GI symptoms and body image documented similar findings. The ROBINS-I tool highlighted a significant risk of bias across the studies. CONCLUSION: Currently, it is not possible to draw a firm conclusion on postoperative QoL, pain, GI symptoms, and body image following restorative or non-restorative surgery. The included studies were generally of poor quality, lacked preoperative evaluations, and showed considerable bias in the data
Dividend Stickiness in Japan
markdownabstract__Abstract__
The paper describes the introduction of an emphasis on âpersonal securityâ in human security thinking and practice, as part of the ultimately unsuccessful attempt to compartmentalize the pursuit of security. It reviews the past twenty years of attention to âpersonal securityâ: both in compartments that consider organized physical violence or threats to personal safety and property (âcitizen securityâ), and as parts of more wide-ranging examination of threats to fulfilment of basic needs and rights, for example in comprehensive mapping exercises undertaken in various UNDP Regional and National Human Development Reports or in studies of womenâs security. The paper reflects on the complex process of opening-up conventional security thinking and practice, seeking value-added and depth without shrinking into preconceived compartments
Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
Background:
Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.
Methods:
We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0â2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).
Findings:
Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86â107) in the abiraterone trial and 72 months (61â74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8â86·9) in the abiraterone group versus 45·7 months (41·6â52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53â0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9â81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3â59·0) in the standard of care group (HR 0·65 [0·55â0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83â1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3â5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial).
Interpretation:
Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.
Funding:
Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas
Keratinocyte Skin Cancers in General Surgery: The Impact of Anaesthesia, Trainee Supervision, and Choice of Reconstruction
Background. Keratinocyte skin cancers are common in Australia, incurring disproportionately high health expenditure in comparison with mortality. General surgeons often excise these lesions as day-surgery. Balancing individual complexities of these cancers with trainee supervision and health expenditure is key to deliver efficacious care and maintain day-surgery volume for patients during a pandemic. Methods. A retrospective, cross-sectional study was performed, examining 414 procedures from January 2019 to December 2020. Pathology was reviewed, and benign lesions excluded. Complete excision was based on 5âmm margins for squamous cell carcinoma (SCC), 0.5âmm microscopic margins for low-risk basal cell carcinoma (BCC) subtypes, and 3âmm for high-risk. Results of trainee-performed local anesthetic (LA) excision and general anesthetic (GA) excision (consultant scrubbed) were compared. Results. 288 excisions were reviewed for completeness, location, and reconstruction modality. 69% were BCC (199), and 31% were SCC (89). These were excised under GA (72.5%) and LA (27.5%). 25.6% of BCC excisions were âclose,â and 22.6% were âpositiveâ under GA, whilst 31% were âcloseâ and 15.5% were âpositiveâ under LA. 52.8% of SCC excisions were âclose,â and 7.8% were âpositiveâ under GA, compared with 42.8% âcloseâ and 9.5% âpositiveâ under LA. Complex reconstruction (skin graft, flap) was more common under GA (38% SCC and 36.1% BCC), but occurred at a modest rate under LA (22% BCC and 28.5% SCC). Conclusions. The results confirm that comparable margins and reconstruction options are achievable when excising keratinocyte cancers under LA by surgical trainees. This is fundamental in cost and timesaving, as well as reducing risk of aerosolisation of virus during GA, in a pandemic
Human security thinking in practice: âpersonal securityâ, âcitizen security' and comprehensive mappings
Bedeutung und Anwendung
Title Page, Table of Contents, Motivation
iv
Concepts
v
Introduction
vii
1 Fundamentals
1
1.1 Meaning of isostasy and rigidity
1
1.1.1 Isostasy according to Pratt
1
1.1.2 Isostasy according to Airy
2
1.1.3 Isostasy according to Vening-Meinesz
2
1.1.4 Elastic thickness and flexural rigidity
4
1.2 Methods for estimation of flexural parameters
5
1.2.1 Spectral methods
5
1.2.2 Advantage and disadvantage of spectral methods
10
1.2.3 Convolution method
11
1.2.4 Advantage and disadvantage of the convolution method
12
1.2.5 Conclusion
12
1.3 Gravity inversion according to Parker algorithm
13
1.3.1 Introduction
13
1.3.2 Method
13
1.3.3 Synthetic example
14
1.4 Internal loads
16
1.4.1 Calculation of gravity effect of sediments with slice program
16
1.4.2 Pseudo topography
17
2 Theoretical basics and development of the analytical solution
19
2.1 Differential equation
19
2.1.1 Plate theory according to Kirchhoff
19
2.1.2 Beam on elastic foundation
20
2.1.3 Application in geological sciences
23
2.2 Formula according to Hertz
25
2.2.1 Investigation of the Logarithm function
27
2.2.2 Investigation of the Sine function
29
2.2.3 Summary of the behavior of the functions
30
2.3 New analytical solution
31
2.3.1 Introduction
31
2.3.2 Modification and substitution
31
2.3.3 Investigation of the graph
33
2.3.4 Unification of the analytical solution
35
2.4 Transfer function
38
2.4.1 Introduction
38
2.4.2 Transfer function
39
2.4.3 Verification of the analytical solution
41
2.4.4 Conclusion.
42
2.5 Comparison with FFT solution
43
2.5.1 Comparison with flexure curves
43
2.5.2 Investigation of dependence from grid parameters
44
2.5.3 Boundary cases for elastic thickness
47
2.5.4 Comparison with Vening-Meinesz solution
49
2.5.5 Conclusion
50
2.6 Software concept
51
2.6.1 Introduction
51
2.6.2 Flexure curves and CMI
52
2.6.3 Radius of convolution
52
2.6.4 Iterative estimation of elastic thickness
54
2.6.5 Elastic thickness distribution
56
2.6.6 Reference depth
57
2.7 Comparison with Finite Element modeling
59
2.7.1 Influence of input parameters
61
2.7.2 Conclusion
69
3\. Application of the analytical solution
70
3.1 Pacific Ocean
71
3.1.1 Input data
71
3.1.2 Preliminary investigations
72
3.1.3 Estimation of gravity CMI
73
3.1.4 Estimation of rigidity And elastic thickness
76
3.1.5 Discussion and conclusion.
77
3.2 Central Andes
80
3.2.1 Input data
80
3.2.2 Preliminary investigation
82
3.2.3 Estimation of rigidity and elastic thickness
83
3.2.4 Discussion and conclusion.
86
3.3 Southern Andes
91
3.3.1 Input data
91
3.3.2 Estimation of rigidity and elastic thickness
92
3.3.3 Discussion and conclusion.
93
4 Discussion of results
98
4.1 Thick plate theory
98
4.2 Influence of temperature
99
4.2.1 Introduction
99
4.2.2 Synthetic example
99
4.2.3 Application in geological sciences
101
4.3 Significance of input parameters
105
4.3.1 Deviation of height
106
4.3.2 Deviation of gravity
107
4.3.3 Deviation of Young's modulus
107
4.3.4 Deviation of Poisson ratio
108
4.3.5 Deviation of density of crust
109
4.3.6 Deviation of density of mantle
109
4.3.7 Deviation of elastic thickness
110
4.3.8 Conclusion
111
4.4 Variation of Young's modulus
112
4.5 Visco-elastic behavior
116
4.6 Final comments and future directions
122
5 Appendix
I
5.1 Density-porosity formula
I
5.2 Comparison of flexure curves
III
5.2.1. FFT solution compared with Logarithm and Sine function
III
5.2.2. Comparison of output from computer program with FFT
IV
5.3 FE models
V
5.3.1. Calculation input parameters and results
VI
5.3.2. Settings of the FE models
IX
Acknowledgement, References
X
Notation
XI
Abbreviations
XIV
Index of Tables
XV
Index of Figures
XVI
ReferencesIn 1939 a new concept was introduced by Vening-Meinesz proposing that the
flexural strength of the lithosphere must be considered for isostatic models.
A 4th order differential equation describing the flexure of a thin plate was
developed. In the past the equation has been solved in frequency space using
spectral methods (coherence and admittance). However, the admittance and
coherence techniques have been questioned when applied to continental
lithosphere. Both methods require an averaging process; therefore the
variation in rigidity may be retrieved only to a limited extent. A large
spatial window with a side length of at least 375 km is required over the
study area. And, in where the input topography is characterized by low
topographic variation, the method becomes unstable. These problems can be
overcome by calculating the flexural rigidity with the convolution approach
and furthermore with the use of a newly derived analytical solution of the
differential equation mentioned above. This solution was developed out of
three solutions from Hertz and has been made applicable to geological science.
The analytical solution has been applied to both oceanic lithosphere (Nazca
plate) and continental lithosphere (Central and Patagonian Andes). The
resulting flexural rigidity values and their variations have been compared
with the ideas and concepts developed by the members of the SFB267 community,
and correlate well with tectonic units and fault systems. In the past the
elastic thickness has been used synonymously for the flexural rigidity.
However, the analytical solution leads to a new interpretation and meaning of
the elastic thickness. It is shown that it is sufficient to operate with a
constant value for both gravity and Poisson's ratio, as the variation of
either parameter does not lead to a significant change in the distribution of
flexural rigidity. Young's modulus is shown to be the driving factor for the
flexural deformation. A temperature moment must also be taken into account in
flexural investigations. Thus, the variation of the elastic thickness can be
explained by temperature distribution and a change of the Young's modulus. A
new definition of elastic thickness can be obtained: the value of the
calculated elastic thickness is equivalent to the value of thickness of a
corresponding plate described by a constant Young's modulus. Computations
using the differential equation are valid for the crust/mantle interface
(Moho) as well as the lithosphere/ asthenosphere boundary. The calculated
boundary surface can be shifted at the position of the boundary at which a
significant change of Young's modulus takes place.Im Jahre 1939 wurde von Vening-Meinesz eine Theorie entwickelt, welche die
RigiditÀt der LithosphÀrenplatte innerhalb isostatischer Betrachtungen
berĂŒcksichtigte. Dazu wurde eine Differentialgleichung 4. Ordnung verwendet,
welche die Deformation einer dĂŒnnen Platte beschreibt. In der Vergangenheit
wurde die Gleichung mittels der Spektralmethoden im Frequenz-Bereich gelöst.
Aber bezĂŒglich der Anwendung der KohĂ€renz- und Admittanzmethode auf die
Kontinente wurde ihre NĂŒtzlichkeit aufgrund der Nachteile, welche durch den
Spektralansatz entstehen, in Frage gestellt. Dieser Ansatz bedingt eine
Durchschnittsbildung, welche im Falle einer sich rÀumlich stark variierenden
RigiditĂ€t dazu fĂŒhren kann, dass jene Variation nur bis zu einem begrenzten
Mabe aufgelöst wird. FĂŒr das Untersuchungsgebiet ist eine SeitenlĂ€nge von
mindestens erforderlich. Ein weiteres Problem tritt im Falle niedriger
Topographie auf, da kleinere Spektralwerte zu Instabilitaeten innerhalb der
Anwendung fĂŒhren können. Durch die Verwendung der Konvolutionsmethode und der
neu entwickelten analytischen Lösung der obig eingefĂŒhrten
Differentialgleichung werden diese Nachteile ĂŒberwunden. Diese analytische
Lösung wurde aus drei verschiedenen Lösungen nach Hertz entwickelt und fĂŒr die
geologischen Wissenschaften anwendbar gemacht. Die analytische Lösung wurde
auf die ozeanische LithosphÀre im Bereich des Pazifik (Nazca-Platte) und auf
die kontinentale LithosphÀre im Bereich der Zentral - und der Patagonischen
Anden angewendet. Die resultierende RigiditÀtsverteilung wird mit den von den
Mitgliedern der SFB267 Gemeinschaft entwickelten Ideen und Konzepten
verglichen, und ist durch eine gute Korrelation mit den tektonischen Einheiten
und Störungssystemen charakterisiert. Bisher wurde die elastische Dicke und
die flexurelle RigiditĂ€t synonym verwendet. Aber die analytische Lösung fĂŒhrte
zu einem neuen VerstÀndnis und Interpretation der elastischen Dicke. In
Anbetracht der Untersuchungen zur Signifikanz der Inputparameter ist es
zulĂ€ssig mit einem konstanten Wert fĂŒr die Schwere und dem Poisson-VerhĂ€ltnis
zu arbeiten, denn dies wird nicht zu signifikanten Unterschieden im Ergebnis
fĂŒhren. Dies gilt nicht fĂŒr das ElastizitĂ€tsmodul, denn dieser Parameter ist
ein entscheidender Faktor fĂŒr das Deformationsverhalten. Daher kann die
elastische Dicke auch als Ă€quivalente Plattendicke fĂŒr eine Platte konstanten
ElastizitÀtsmoduls definiert werden. Zudem wurde herausgefunden, daà das
Temperaturmoment in den weiteren Untersuchungen mit berĂŒcksichtigt werden
muss. Damit kann die beobachtete Variation der elastischen Dicke durch die
Temperaturverteilung und die VerÀnderung des ElastizitÀtsmoduls erklÀrt
werden. ZusÀtzlich wurde gezeigt, daà die Berechnungen mittels der
Differentialgleichung und der analytischen Lösung sowohl fĂŒr die
Krusten/Mantel Grenze als auch die LithosphĂ€ren/AsthenosphĂ€ren Grenze gĂŒltig
sind. Dabei ist entscheidend, an welcher GrenzflÀche sich das
ElastizitÀtsmodul Àndert