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Moving GLUT4: The Biogenesis and Trafficking of GLUT4 Storage Vesicles

Shane Rea
Nov 1, 1997; 46:1667-1677
Perspectives in Diabetes




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Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles




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Evidence for 5'AMP-Activated Protein Kinase Mediation of the Effect of Muscle Contraction on Glucose Transport

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications




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Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article




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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action

D A Pan
Jun 1, 1997; 46:983-988
Original Article




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Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha}

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications




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Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications




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The Triumvirate: {beta}-Cell, Muscle, Liver: A Collusion Responsible for NIDDM

Ralph A DeFronzo
Jun 1, 1988; 37:667-687
Lilly Lecture 1987




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Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes

David E. Kelley
Oct 1, 2002; 51:2944-2950
Metabolism and Signal Transduction




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Why can’t vehicle registration be renewed online?

THE EDITOR, Madam: I arrived at the Constant Spring tax office at 6:05 a.m. on Monday, May 4 to renew my vehicle registration. At that hour, there were already 30 persons ahead of me. Persons related horror stories of spending up to five hours in...




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Perivascular Adipose Tissue Controls Insulin-Stimulated Perfusion, Mitochondrial Protein Expression, and Glucose Uptake in Muscle Through Adipomuscular Arterioles

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine," signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.




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A Single Bout of One-Legged Exercise to Local Exhaustion Decreases Insulin Action in Nonexercised Muscle Leading to Decreased Whole-Body Insulin Action

A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise. Whole-body glucose disposal was ~18% lower on the exercise day as compared with the resting day due to decreased (~37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle on the exercise day, suggesting that decreased insulin action in nonexercised muscle may reduce GLUT4 translocation in response to insulin. Thus, the effect of a single bout of exercise on whole-body insulin action depends on the balance between local effects increasing and systemic effects decreasing insulin action. Physiologically, this mechanism may serve to direct glucose into the muscles in need of glycogen replenishment. For insulin-treated patients, this complex relationship may explain the difficulties in predicting the adequate insulin dose for maintaining glucose homeostasis following physical activity.




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A Wider Circle? The Circular Economy in Developing Countries

5 December 2017

Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity.

Felix Preston

Former Senior Research Fellow and Deputy Research Director, Energy, Environment and Resources

Johanna Lehne

Former Research Associate, Energy, Environment and Resources

2017-12-05-circular-economy.jpg

A stack of recycled paper ready to be bound into books at a workshop in Kolkata, India. Photo: Felix Preston.

Summary

  • There is growing optimism about the potential of the ‘circular economy’ (CE) as a new model for sustainable growth in developing countries. A CE is one in which products are recycled, repaired or reused rather than thrown away, and in which waste from one process becomes an input into other processes. In recent months there has been CE-related activity in countries as diverse as Laos, Rwanda and Colombia.
  • A CE strategy could help lower-income countries ‘leapfrog’ to a more sustainable development pathway that avoids locking in resource-intensive practices and infrastructure. But a stronger evidence base is needed to show how the agenda can deliver opportunities for industrialization, as well as addressing environmental insecurity.
  • Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity. Much economic activity in lower-income countries revolves around sorting and reusing waste. However, higher-value, employment-generating opportunities for reuse and remanufacturing are yet to be captured.
  • The existence of circular activities in developing countries provides excellent political ‘entry points’, which could enable governments, the private sector, civil society and other actors to promote innovative economic models. The CE could provide a powerful narrative, helping to build momentum around a set of ideas that can be applied in and tailored to multiple sectors or cities.
  • There is a window of opportunity in which to align the efforts of development organizations and partner countries. Donors are exploring how the agenda should be aligned with the Sustainable Development Goals (SDGs) and the Paris Climate Agreement. Wider international cooperation on the CE could involve trade partnerships, regional hubs or pilot zones.




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Nuclear Energy in a Post-Brexit Europe

Invitation Only Research Event

11 October 2019 - 8:30am to 10:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Tim Yeo, Chairman, The New Nuclear Watch Institute
Chair: Antony Froggatt, Senior Research Fellow, Energy, Environment and Resources, Chatham House 

Brexit will significantly change the balance within the EU in relation to nuclear energy. Apart from France and Finland, both of whose nuclear development programmes are behind schedule, the UK is the only member state in northern or western Europe currently investing in new nuclear capacity. Brexit will therefore leave the supporters of nuclear energy within the EU27 and the European Commission in a weaker position.

The speaker will argue that at a time when the energy industry needs to accelerate its shift away from fossil fuels, and when the electricity generation industry must cut its carbon emissions faster than it has ever managed to do in the past, this change is unhelpful.

The workshop will also address the need for additional interconnector capacity and the future of carbon-trading outside the EU emission trading system and how this relates to potential nuclear energy capacity.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Chloé Prendleloup




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Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology]

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.




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The Future of Enrichment: Math Contests or Math Circles?

by Doug O’Roark Executive Director, Math Circles of Chicago The New York Times recently published an article entitled “The Right Answer? 8,186,699,633,530,061 (An Abacus Makes It Look Almost Easy)”. Its lead photograph features over 100 children seated at desks, facing … Continue reading




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Cleveland Cavaliers planning to reopen training facility Friday

The Cleveland Cavaliers are planning to reopen their training facility for limited individual workouts amid the coronavirus pandemic.




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U.S. Navy ships, trailed by Russia, visit Barents Sea above Arctic Circle

U.S. Navy ships on Monday entered the Barents Sea between Norway and Russia, for the first time since the 1980s, "to assert freedom of navigation and demonstrate seamless integration among allies," the U.S. Navy said.




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Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance

OBJECTIVE

Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.

RESEARCH DESIGN AND METHODS

Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined.

RESULTS

Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ~30% and ~40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ~20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

CONCLUSIONS

In obese humans with microvascular insulin resistance, GLP-1’s vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.




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“Cubicle Activism”: Companies Face Growing Demands from Workers to Cut Ties with ICE and Others in Immigration Arena

From online petitions to organized walkouts, corporate America is facing increasing employee activism over its business involvement with agencies implementing the federal government's immigration policies. This "cubicle activism," seen at companies ranging from Amazon and Google to Bank of America and Wayfair, has garnered mixed success to date, forcing divestiture from private prison contractors but fewer results in other contexts, as this article explores.




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UCLA dental school researchers create nanoparticle that could improve bone defect treatment

A team of researchers at the University of California, Los Angeles School of Dentistry has developed a nanoparticle that could improve treatment for bone defects.




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Dow, Total part of group that raised $1B to clean plastic in ocean

Some 30 companies including Dow, Total and other big makers of plastic raised $1 billion to contribute to cleaner ocean waters.




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Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits

OBJECTIVE

We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study.

RESEARCH DESIGN AND METHODS

We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18–65 years, mean BMI >40 kg/m2, mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models.

RESULTS

During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m2.

CONCLUSIONS

Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.




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Coldest material in the cosmos could help scientists find dark matter particles

Researchers suggest the coldest material in the universe could reveal the presence of dark matter particles.




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[ Singles & Dating ] Open Question : The man that’s showed clear/obvious interest in me had no contact with me yesterday, is this normal?

I’ve been talking to a man, we have mutual interest in each other. We talked on the phone for over an hour the night before last and it was an amazing conversation. The next day he had no contact with me, which in my mind it didn’t bother me and still kind of isn’t I think he just is doing his own thing and likes his personal space. I’m not too bothered or worried but still questioning why? Is it normal for a man to kinda disappear and have no contact for a day?




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CROSSWORD! (or: Diversion as a vehicle for conversation on power and usage)

There is so much that is peculiar, irregular, silly, or downright twisted in mathematical verbiage that, certainly, we could all benefit from some soul-searching on the language of our culture. Some of mathematics usage is confusing (e. g. overuse of … Continue reading




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Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils [Computational Biology]

Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis.




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Spring cleansing beetroot and pomegranate salad

Beets have strong detoxifying properties, as they are high in chlorine, which assists in the cleansing of the liver, kidneys and bloodstream. They are also rich in potassium, which balances the metabolism. The mighty beets nourish the blood, tonify the heart, calm the spirit and nervousness, and they lubricate the intestines and cleanse the liver! Oh my giddy Aunt!




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Review Article – Within a single lifetime: Recent writings on autism

AHP readers will be interested in a review article now available online from History of the Human Sciences “Within a single lifetime: Recent writings on autism.” Written by Gregory Hollin the piece reviews five recent books on autism.




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Forthcoming in JHBS: Quêtelet on Deviance, McClelland on Leadership, Psychological Warfare, and More

A number of articles now in press at the Journal of the History of the Behavioral Sciences will be of interest to AHP readers. Full details below. “Uncovering the metaphysics of psychological warfare: The social science behind the Psychological Strategy Board’s operations planning, 1951–1953,” Gabrielle Kemmis. Abstract: In April 1951 president Harry S. Truman established … Continue reading Forthcoming in JHBS: Quêtelet on Deviance, McClelland on Leadership, Psychological Warfare, and More




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Casindra lost : the Paradisi Chronicles / Marti Ward.

A 3.5 year mission from which they'll never return, a 2.5 million lightyear journey to another galaxy, 1.5 crew members comprising a solitary captain and a half-baked AI... Captain Sideris is a loner and knows LETO ships like nobody else, having risen to command the Lunar-Earth construction fleet, as they build ships to mine asteroids and colonize Mars. Suddenly he finds the colonization effort is for another planet, in another galaxy, and he's the sole human guinea pig being gated through a wormhole with an AI playing Noah to LETO SS Casindra's ark. Everything goes well as he starts to survey four planets they plan to exploit, as he gets to know emergent AI 'Al', as he discovers he's building a special relationship with empathic cat 'Simba'. Problem is message drones gated home are not being returned per protocol, with little explanation, no supplies, and some cryptic and disturbing messages. This full length novel is set in the multi-author multi-genre Paradisi universe. Casindra Lost opens the Lost Mission Series to explain what happened to some of the early missions that underlie the various colonization and post-colonization stories.




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The Death Cycle of Companies.




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"That's what she said" : how to draft a clear and effective affidavit in family law / paper presented by Marita Pangallo, Howard Zelling Chambers and Daniel Praolini, Capmpbell Chambers.




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UNCLE SILAS 1 : GENETIS.




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Vehicle speeds in South Australia 2018 : CASR155.




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An evaluation of bicycle passing distances in the ACT / JRR Mackenzie, JK Dutschke, G Ponte.

To evaluate bicycle passing distances in the Australian Capital Territory (ACT), specialised passing distance measurement devices (PDMDs) were installed on a sample of 23 cyclists who ride in the ACT. Passing distance data and GPS data was collected by cyclists using the PDMDs for a four week period, during a trial phase of a newly legislated minimum passing distance (MPD) rule The MPD rule requires drivers to provide more than 1 metre of space when passing a cyclist on a road with a speed limit of 60 km/h or below, and 1.5 meters of space when passing a cyclist on a road with a speed limit above 60 km/h.-- Abstract.




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Exploring the prevalence of in-vehicle driver distraction in moving traffic : a pilot study / G Ponte, LN Wundersitz.




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Clearing the air : the beginning and the end of air pollution / Tim Smedley.

Air -- Pollution.




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Boys will be boys / Clementine Ford.

Men -- Australia -- Social conditions.




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Trailblazers : 100 inspiring South Australian women / Carolyn Collins and Roy Eccleston.

Women -- South Australia -- Biography.




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Spring clean your legal pamphlets

Legal Aid NSW have recently updated some of their most popular pamphlets. What happens when your relationship ends wa




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Des lesions veineuses chez les arteriosclereux / par Henry Thiebaut.

Paris : G. Masson, 1890.




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Des maladies foetales qui peuvent faire obstacle à l'accouchement : thèse ... / par Alphonse Herrgott.

Paris : O. Doin, 1878.




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Des moyens simples a employer pour guerir et eviter la tuberculose / par Jeanne Leclerc.

Paris : Société d’éditions scientifiques, 1896.




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Des reflexes tendineux / par Constant Petitclerc.

Paris : A. Delahaye et E. Lecrosnier, 1880.




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Diabetes : its pathological physiology / by John J.R. Macleod.

London : Edward Arnold, 1913.




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Die paralytischen Anfalle : klinischer Vortrag / von Clemens Neisser.

Stuttgart : F. Enke, 1894.




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Die Sclerodermie : eine monographische Studie / von Georg Lewin und Julius Heller.

Berlin : A. Hirschwald, 1895.




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Dirty dustbins and sloppy streets : a practical treatise on the scavenging and cleansing of cities and towns / by H. Percy Boulnois.

[London] : E. & F.N. Spon, 1881.




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A dissertation on the varied direction of the fibres of the muscles, and on the effects of this upon the movements of the body : with an appendix ... / by Alex. Monro.

Edinburgh : [publisher not identified], 1812.