The Attorney-Client Privilege

History suggests that the attorney-client privilege is the oldest of the evidentiary privileges. It probably arose at common law during the 1500\u27s, concurrent with the right to trial by jury. Judges initially viewed the privilege as a vindication of the oath and the honor of the attorney. However, during the late 1700\u27s, courts began to assert that the privilege\u27s purpose was to encourage clients to make full disclosure to their counsel, by providing subjectively for the client\u27s freedom of apprehension. In 1871, the Virginia Supreme Court5 stated that [i]f the privilege did not exist at all, every one would be thrown upon his own legal resources; deprived of all professional assistance, a man would not venture to consult any skillful person, or would only dare to tell his counsel half his case. Today, courts continue to state that the benefits of full disclosure justify the privilege, and frequently assert that without such full disclosure an attorney may not be able to adequately advise his client

Baryon charge from embedding topology and a continuous meson spectrum in a new holographic gauge theory

We study a new holographic gauge theory based on probe D4-branes in the background dual to D4-branes on a circle with antiperiodic boundary conditions for fermions. Field theory configurations with baryons correspond to smooth embeddings of the probe D4-branes with nontrivial winding around an S^4 in the geometry. As a consequence, physics of baryons and nuclei can be studied reliably in this model using the abelian Born-Infeld action. However, surprisingly, we find that the meson spectrum is not discrete. This is related to a curious result that the action governing small fluctuations of the gauge field on the probe brane is the five-dimensional Maxwell action in Minkowski space despite the non-trivial embedding of the probe brane in the curved background geometry.Comment: 24 pages, LaTeX, 10 figures, v4: previously ignored effects of coupling to RR-fields included, meson spectrum qualitatively changed, v5: journal versio

Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

Numerical analysis of high-power X-band sources, at low magnetic confinement, for use in a multi-source array

High-power microwave sources are typically relativistic in nature, employing multi-kilo-ampere electron beams that require significant magnetic confinement for efficient operation. As the desired output power increases so does the complexity, and overall energy requirements, of the source. It can therefore be advantageous to consider the use of several, moderate-power, sources operating as a phased array; for an array of N sources the far-field peak intensity scales as N2, and the peak-of-field may be steered electronically by varying the relative phases of the different output signals. In this paper we present the numerical analysis of a short-pulse (∼1ns) X-band backward-wave oscillator, driven by a 210keV, 1.4kA electron beam, suitable for use as the radiative element in such an array. Investigation of the required magnetic confinement showed two peaks in performance, with the highest efficiency, of 43%, predicted at the low magnetic confinement peak at 0.3T, corresponding to 125MW peak output power. The magnitude, and timing, of the peak in the output pulse were functions of the rise-time of the electron beam energy, with longer rise-times resulting in delayed peak-of-field and lower peak output power. When operating in an array, to maintain effective output in the region of N2, it was determined that the beam rise-times, across all sources, should be ≤150ps with the adjustment of the relative timing between output’s being ±30ps

CaMKK2 as an emerging treatment target for bipolar disorder

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder

Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock

Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock

Comparison of tungsten nano-tendrils grown in Alcator C-Mod and linear plasma devices

Growth of tungsten nano-tendrils (“fuzz”) has been observed for the first time in the divertor region of a high-power density tokamak experiment. After 14 consecutive helium L-mode discharges in Alcator C-Mod, the tip of a tungsten Langmuir probe at the outer strike point was fully covered with a layer of nano-tendrils. The depth of the W fuzz layer (600 ± 150 nm) is consistent with an empirical growth formula from the PISCES experiment. Re-creating the C-Mod exposures as closely as possible in Pilot-PSI experiment can produce nearly-identical nano-tendril morphology and layer thickness at surface temperatures that agree with uncertainties with the C-Mod W probe temperature data. Helium concentrations in W fuzz layers are measured at 1–4 at.%, which is lower than expected for the observed sub-surface voids to be filled with several GPa of helium pressure. This possibly indicates that the void formation is not pressure driven.United States. Dept. of Energy (Award DE-SC00-02060

Hemorrhage-Adjusted Iron Requirements, Hematinics and Hepcidin Define Hereditary Hemorrhagic Telangiectasia as a Model of Hemorrhagic Iron Deficiency

BACKGROUND: Iron deficiency anemia remains a major global health problem. Higher iron demands provide the potential for a targeted preventative approach before anemia develops. The primary study objective was to develop and validate a metric that stratifies recommended dietary iron intake to compensate for patient-specific non-menstrual hemorrhagic losses. The secondary objective was to examine whether iron deficiency can be attributed to under-replacement of epistaxis (nosebleed) hemorrhagic iron losses in hereditary hemorrhagic telangiectasia (HHT). METHODOLOGY/PRINCIPAL FINDINGS: The hemorrhage adjusted iron requirement (HAIR) sums the recommended dietary allowance, and iron required to replace additional quantified hemorrhagic losses, based on the pre-menopausal increment to compensate for menstrual losses (formula provided). In a study population of 50 HHT patients completing concurrent dietary and nosebleed questionnaires, 43/50 (86%) met their recommended dietary allowance, but only 10/50 (20%) met their HAIR. Higher HAIR was a powerful predictor of lower hemoglobin (p = 0.009), lower mean corpuscular hemoglobin content (p<0.001), lower log-transformed serum iron (p = 0.009), and higher log-transformed red cell distribution width (p<0.001). There was no evidence of generalised abnormalities in iron handling Ferritin and ferritin(2) explained 60% of the hepcidin variance (p<0.001), and the mean hepcidinferritin ratio was similar to reported controls. Iron supplement use increased the proportion of individuals meeting their HAIR, and blunted associations between HAIR and hematinic indices. Once adjusted for supplement use however, reciprocal relationships between HAIR and hemoglobin/serum iron persisted. Of 568 individuals using iron tablets, most reported problems completing the course. For patients with hereditary hemorrhagic telangiectasia, persistent anemia was reported three-times more frequently if iron tablets caused diarrhea or needed to be stopped. CONCLUSIONS/SIGNIFICANCE: HAIR values, providing an indication of individuals' iron requirements, may be a useful tool in prevention, assessment and management of iron deficiency. Iron deficiency in HHT can be explained by under-replacement of nosebleed hemorrhagic iron losses