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Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.
Understanding patient preferences and the demand for healthcare interventions and technology is critical for health technology assessment (HTA). New health technologies have potential for savings and increased efficiency but even the most cost-effective and efficacious interventions can fail if patient preferences are not properly accounted for. Patient preferences in HTA are primarily limited to representation in appraisal committees; however, more robust methods are available and should be incorporated into the assessment of interventions.
Methods
Using data from three discrete choice experiments (DCEs), we reflect on the importance of patient preferences in the design of healthcare interventions. We draw insights from three studies which investigated preferences relating to HIV self-testing amongst long distance truck drivers in Kenya; differentiated antiretroviral therapy services amongst stable HIV patients in Zimbabwe; and tuberculosis preventive therapy for children in Eswatini.
Results
We highlight three key findings. First, understanding patient preferences is crucial when designing services, and providers sometimes underestimate behavioural barriers and overestimate the extent to which people are motivated simply by health benefits. Optimism is often driven by evidence showing high acceptability, but when preference structures are incorporated in intervention design, there are important insights into how patients plan to utilize services. Second, trade-offs matter in determining which characteristics are perceived to be most important to patients – a key strength of the DCE methodology. Understanding of these trade-offs can help prioritize which characteristics of interventions to target. Finally, disentangling the effect of different characteristics of service delivery models on preferences is important for rethinking how interventions are delivered. If services are designed to better align with preferences, implementers can ensure new interventions have the desired effect on health and economic outcomes.
Conclusions
These findings highlight the value of behavioural economic approaches for investigating preferences for health interventions and providing insights into the demand for services, which must feed into the HTA analyses. Incorporating DCEs into HTA is inexpensive and provides robust data for improving HTA.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Surgical site infections (SSIs) are common surgical complications that lead to increased costs. Depending on payer type, however, they do not necessarily translate into deficits for every hospital.
Objective:
We investigated how surgical site infections (SSIs) influence the contribution margin in 2 reimbursement systems based on diagnosis-related groups (DRGs).
Methods:
This preplanned observational health cost analysis was nested within a Swiss multicenter randomized controlled trial on the timing of preoperative antibiotic prophylaxis in general surgery between February 2013 and August 2015. A simulation of cost and income in the National Health Service (NHS) England reimbursement system was conducted.
Results:
Of 5,175 patients initially enrolled, 4,556 had complete cost and income data as well as SSI status available for analysis. SSI occurred in 228 of 4,556 of patients (5%). Patients with SSIs were older, more often male, had higher BMIs, compulsory insurance, longer operations, and more frequent ICU admissions. SSIs led to higher hospital cost and income. The median contribution margin was negative in cases of SSI. In SSI cases, median contribution margin was Swiss francs (CHF) −2045 (IQR, −12,800 to 4,848) versus CHF 895 (IQR, −2,190 to 4,158) in non-SSI cases. Higher ASA class and private insurance were associated with higher contribution margins in SSI cases, and ICU admission led to greater deficits. Private insurance had a strong increasing effect on contribution margin at the 10th, 50th (median), and 90th percentiles of its distribution, leading to overall positive contribution margins for SSIs in Switzerland. The NHS England simulation with 3,893 patients revealed similar but less pronounced effects of SSI on contribution margin.
Conclusions:
Depending on payer type, reimbursement systems with DRGs offer only minor financial incentives to the prevention of SSI.
We present ALMA [CII] line and far-infrared (FIR) continuum observations of seven z > 6 low-luminosity quasars (M1450 > −25 mag) discovered by our on-going Subaru Hyper Suprime-Cam survey. The [CII] line was detected in all targets with luminosities of ∼(2−10) × 108 L⊙, about one order of magnitude smaller than optically luminous quasars. Also found was a wide scatter of FIR continuum luminosity, ranging from LFIR < 1011L⊙ to ∼2 × 1012L⊙. With the [CII]-based dynamical mass, we suggest that a significant fraction of low-luminosity quasars are located on or even below the local Magorrian relation, particularly at the massive end of the galaxy mass distribution. This is a clear contrast to the previous finding that luminous quasars tend to have overmassive black holes relative to the relation. Our result is expected to show a less-biased nature of the early co-evolution of black holes and their host galaxies.
A lasting legacy of the International Polar Year (IPY) 2007–2008 was the promotion of the Permafrost Young Researchers Network (PYRN), initially an IPY outreach and education activity by the International Permafrost Association (IPA). With the momentum of IPY, PYRN developed into a thriving network that still connects young permafrost scientists, engineers, and researchers from other disciplines. This research note summarises (1) PYRN’s development since 2005 and the IPY’s role, (2) the first 2015 PYRN census and survey results, and (3) PYRN’s future plans to improve international and interdisciplinary exchange between young researchers. The review concludes that PYRN is an established network within the polar research community that has continually developed since 2005. PYRN’s successful activities were largely fostered by IPY. With >200 of the 1200 registered members active and engaged, PYRN is capitalising on the availability of social media tools and rising to meet environmental challenges while maintaining its role as a successful network honouring the legacy of IPY.
Early Archaic human skeletal remains found in a burial context in Lapa doSanto in east-central Brazil provide a rare glimpse into the lives ofhunter-gatherer communities in South America, including their rituals fordealing with the dead. These included the reduction of the body by means ofmutilation, defleshing, tooth removal, exposure to fire and possiblycannibalism, followed by the secondary burial of the remains according tostrict rules. In a later period, pits were filled with disarticulated bonesof a single individual without signs of body manipulation, demonstratingthat the region was inhabited by dynamic groups in constant transformationover a period of centuries.
This timely book answers complex and perplexing questions raised by Wall Street's role in the financial crisis. What are the economic and moral connections between Wall Street and the overall economy? How did we arrive at this point in history where our most powerful financial institutions thwart rather than promote free markets, prosperity and even social cohesion? Can the fractured relationship between Wall Street and Main Street be repaired? Wall Street Values chronicles the transformation of Wall Street's business model from serving clients to proprietary trading and explains how this shift undermined the ethical foundations of the modern financial industry. Michael A. Santoro and Ronald J. Strauss argue that post-millennial Wall Street is not only 'too big to fail' but also a threat to the economy even when it succeeds.
Still, if you will not fight for the right when you can easily win without bloodshed, if you will not fight when your victory will be sure and not so costly, you may come to the moment when you will have to fight with all the odds against you and only a precarious chance for survival.
Sir Winston Churchill, The Gathering Storm (1948)
We do not accept the view that regulators lacked the power to protect the financial system. They had ample power in many arenas and they chose not to use it. To give just three examples: the Securities and Exchange Commission could have required more capital and halted risky practices at the big investment banks. It did not. The Federal Reserve Bank of New York and other regulators could have clamped down on Citigroup’s excesses in the run-up to the crisis. They did not. Policy makers and regulators could have stopped the runaway mortgage securitization train. They did not. In case after case after case, regulators continued to rate the institutions they oversaw as safe and sound even in the face of mounting troubles, often downgrading them just before their collapse. And where regulators lacked authority, they could have sought it. Too often, they lacked the political will – in a political and ideological environment that constrained it – as well as the fortitude to critically challenge the institutions and the entire system they were entrusted to oversee.
The Financial Crisis Inquiry Commission Report (2011)
Introduction: Ideology Overwhelms Experience
The financial crisis sprang from two mutually reinforcing institutional transformations – one on Wall Street and another in Washington. Fueled by an explosive mix of megamergers, massive capital formation, increased leverage, and runaway technical wizardry, the Wall Street business model evolved from providing a diversified mix of financial services for valued clients to one dominated by the investment of a firm’s own capital in increasingly complex and risky securities, often at the expense of a firm’s customers who came to be viewed as counterparties. The most telltale sign of Wall Street’s transformation was the exponential growth and increasing importance of precisely the kind of proprietary trading, particularly of CMOs, at the center of the financial crisis. Facilitating all this was a parallel retreat in Washington’s oversight of the financial industry.
On Monday, September 15, 2008, Lehman Brothers, a prominent investment bank that traces its roots to 1850, declared bankruptcy and thereupon triggered a global financial crisis. Literally overnight, borrowing came to a standstill, and widely held assets could not be converted into cash. The liquidity crunch immediately crippled banks owning substantial amounts of securities linked to subprime mortgages and spread very quickly to every sector of the global economy and all types of debt securities. Unable to sell even normally safe and highly liquid investments, on Tuesday, September 16, 2008, the Primary Reserve Fund, the oldest money market fund in the United States, in an action eerily reminiscent of Depression-era bank runs, shocked the financial community by freezing customer accounts and indefinitely halting withdrawals. Ordinary consumers were thus harshly reminded that there were no safe havens for their savings in this economic storm, adding another layer of uncertainty and instability to the financial markets. Within weeks of the Lehman bankruptcy, the resulting shock to the financial system inflicted severe and long-lasting damages on the economy, throwing tens of millions of people out of work and slowing economic growth. Half a decade later, the global economy still limps along in the aftermath of the financial crisis.
The financial crisis sprang from a precipitous decline in the value of mortgage-related securities. The bursting of the mortgage bubble completely wiped out Lehman’s capital base. Other venerable Wall Street institutions including Merrill Lynch and Bear Stearns narrowly averted total collapse through hastily arranged mergers with Bank of America and JPMorgan Chase, respectively. Virtually every major financial institution had massive exposure to the mortgage market relative to its capital base, and even those banks not in danger of imminent collapse suffered staggering losses severely limiting their ability to engage in ordinary consumer lending activities and basic interbank transactions. Because of the financial sector’s centrality to capital and credit markets, the U.S. Congress authorized a $700 billion government bailout to prevent further failures and safeguard the financial system from total collapse.
Beginning roughly in the last two decades of the twentieth century and culminating with the 2008 financial crisis, the dominant Wall Street business model transformed from a customer-driven focus with a minor proprietary trading component to one where principal transactions, and in particular trading in mortgage-backed securities, came to dominate the profits and attention of the brightest minds in the financial industry. This transformation represents a major shift in Wall Street’s business model. The bulk of Wall Street’s profits today are no longer derived from providing financial services to clients. Instead, Wall Street firms generate profits mostly from investing their own capital. The rise of principal transactions occurred not coincidentally just as the financial industry was also experiencing enormous growth in scale as, in the two decades preceding the financial crisis, every major Wall Street firm went from being a privately funded partnership to a publicly held company.
In Chapter two we introduced the idea that profit disjunction occurs when the profits of Wall Street are not aligned with the prosperity of the economy as a whole. In this chapter, we examine how Wall Street profits became unhinged from and dangerous to the general welfare of society. We describe not only how Wall Street became dependent on proprietary trading and the perverse compensation incentives encouraging moral hazard and excessive risk taking, but also how Wall Street became so large that its potential failure as a business sector threatened the stability of the global economy. Our purpose in doing so is not simply to address the issue of “too big to fail” and the bailout. Our objective is to demonstrate how the shift in Wall Street’s business model from serving clients to proprietary trading accompanied a crisis in Wall Street values that in no small measure contributed to the financial crisis. We are concerned, in other words, not only with the threats Wall Street poses to the general economy when it fails, but also with the dangers it creates when it is successful following the postmillennial proprietary trading business model. We begin our analysis, however, by recalling a long bygone era when ongoing customer relations, based upon trust and mutuality, were an essential foundation for the creation and success of the financial industry.
Government can help align Wall Street interests with those of Main Street by channeling self-interested behavior into socially useful outcomes. It can serve as a watchdog, attempting to detect and prevent illegal behavior. Government cannot, however, replace the role of business ethics. Despite numerous regulatory failures and outsized errors in business judgment, the financial crisis was fundamentally a moral crisis. At great cost, we learned that greed, unless tempered by good values, does not “work” from a social perspective. Ethically unmoored, Wall Street became a danger to free markets, the economy, and itself. Only a massive public bailout saved it from the consequences of its own moral decay.
Wall Street today remains morally adrift. It no longer adheres to the customer-driven values that sustained it since the 1930s, yet it has not adopted values and ethical principles suitable for its evolving business models. It lurches along in a moral wasteland from which it may take years, if not decades, to emerge. The prototypical postmillennial Wall Street executive is ethically untroubled, even when securities sold to clients are virtually assured to lose value. Goldman Sachs CEO Lloyd Blankfein captured the essence of this moral sensibility when he described his formative experience at the firm’s commodities trading unit: “We didn’t have the word ‘client’ or ‘customer,’ we had “counterparties” – and that’s because we didn’t know how to spell the word ‘adversary.’” In an earlier era, Wall Street professionals would not have tolerated this kind of sentiment or rampant abuse of customers. However, the postmillennial financial executive lacks relevant principles for sound ethical judgment. The values of the past no longer apply, but no principles have emerged to replace them. In earlier chapters we analyzed how Wall Street arrived at this moral quagmire. In this chapter we consider the prospects for restoring values to a central role on Wall Street.