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\"Malaya, 1945. Cecily Alcantara's family is in terrible danger: her fifteen-year-old son, Abel, has disappeared, and her youngest daughter, Jasmin, is confined in a basement to prevent being pressed into service at the comfort stations. Her eldest daughter Jujube, who works at a tea house frequented by drunk Japanese soldiers, becomes angrier by the day. Cecily knows two things: that this is all her fault; and that her family must never learn the truth. A decade prior, Cecily had been desperate to be more than a housewife to a low-level bureaucrat in British-colonized Malaya. A chance meeting with the charismatic General Fuijwara lured her into a life of espionage, pursuing dreams of an \"Asia for Asians.\" Instead, Cecily helped usher in an even more brutal occupation by the Japanese. Ten years later as the war reaches its apex, her actions have caught up with her. Now her family is on the brink of destruction--and she will do anything to save them. Spanning years of pain and triumph, told from the perspectives of four unforgettable characters, The Storm We Made is a dazzling saga about the horrors of war; the fraught relationships between the colonized and their oppressors, and the ambiguity of right and wrong when survival is at stake\"-- Provided by publisher.

Background Despite the overall effectiveness of total hip arthroplasty (THA), a subset of patients remain dissatisfied with their results because of persistent pain or functional limitations. It is therefore important to develop predictive tools capable of identifying patients at risk for poor outcomes before surgery. Questions/purposes The purpose of this study was to use preoperative patient-reported outcome measure (PROM) scores to predict which patients undergoing THA are most likely to experience a clinically meaningful change in functional outcome 1 year after surgery. Methods A retrospective cohort study design was used to evaluate preoperative and 1-year postoperative SF-12 version 2 (SF12v2) and Hip Disability and Osteoarthritis Outcome Score (HOOS) scores from 537 selected patients who underwent primary unilateral THA. Minimum clinically important differences (MCIDs) were calculated using a distribution-based method. A receiver operating characteristic analysis was used to calculate threshold values, defined as the levels at which substantial changes occurred, and their predictive ability. MCID values for HOOS and SF12v2 physical component summary (PCS) scores were calculated to be 9.1 and 4.6, respectively. We analyzed the effect of SF12v2 mental component summary (MCS) scores, which measure mental and emotional health, on SF12v2 PCS and HOOS threshold values. Results Threshold values for preoperative HOOS and PCS scores were a maximum of 51.0 (area under the curve [AUC], 0.74; p < 0.001) and 32.5 (AUC, 0.62; p < 0.001), respectively. As preoperative mental and emotional health improved, which was reflected by a higher MCS score, HOOS and PCS threshold values also increased. When preoperative mental and emotional health were taken into account, both HOOS and PCS threshold values’ predictive ability improved (AUCs increased to 0.77 and 0.69, respectively). Conclusions We identified PROM threshold values that predict clinically meaningful improvements in functional outcome after THA. Patients with a higher level of preoperative function, as suggested by HOOS or PCS scores above the defined threshold values, are less likely to obtain meaningful improvement after THA. Lower preoperative mental and emotional health decreases the likelihood of achieving a clinically meaningful improvement in function after THA. The results of this study may be used to facilitate discussion between physicians and patients regarding the expected benefit after THA and to support the development of patient-based informed decision-making tools. For example, despite significant disease, patients with high preoperative function, as measured by PROM scores, may choose to delay surgery given the low likelihood of experiencing a meaningful improvement postoperatively. Similarly, patients with notably low MCS scores might best be counseled to address mental health issues before embarking on surgery. Level of Evidence Level III, prognostic study.

Background Revision THA and TKA are growing and important clinical and economic challenges. Healthcare systems tend to combine revision joint replacement procedures into a single service line, and differences between revision THA and revision TKA remain incompletely characterized. These differences carry implications for guiding care and resource allocation. We therefore evaluated epidemiologic trends associated with revision THAs and TKAs. Questions/purposes We sought to determine differences in (1) the number of patients undergoing revision TKA and THA and respective demographic trends; (2) differences in the indications for and types of revision TKA and THA; (3) differences in patient severity of illness scoring between THA and TKA; and (4) differences in resource utilization (including cost and length of stay [LOS]) between revision THA and TKA. Methods The Nationwide Inpatient Sample (NIS) was used to evaluate 235,857 revision THAs and 301,718 revision TKAs between October 1, 2005 and December 31, 2010. Patient characteristics, procedure information, and resource utilization were compared across revision THAs and TKAs. A revision burden (ratio of number of revisions to total number of revision and primary surgeries) was calculated for hip and knee procedures. Severity of illness scoring and cost calculations were derived from the NIS. As our study was principally descriptive, statistical analyses generally were not performed; however, owing to the large sample size available to us through this NIS analysis, even small observed differences presented are likely to be highly statistically significant. Results Revision TKAs increased by 39% (revision burden, 9.1%–9.6%) and THAs increased by 23% (revision burden, 15.4%–14.6%). Revision THAs were performed more often in older patients compared with revision TKAs. Periprosthetic joint infection (25%) and mechanical loosening (19%) were the most common reasons for revision TKA compared with dislocation (22%) and mechanical loosening (20%) for revision THA. Full (all-component) revision was more common in revision THAs (43%) than in TKAs (37%). Patients who underwent revision THA generally were sicker (> 50% major severity of illness score) than patients who underwent revision TKA (65% moderate severity of illness score). Mean LOS was longer for revision THAs than for TKAs. Mean hospitalization costs were slightly higher for revision THA (USD 24,697 +/− USD 40,489 [SD]) than revision TKA (USD 23,130 +/− USD 36,643 [SD]). Periprosthetic joint infection and periprosthetic fracture were associated with the greatest LOS and costs for revision THAs and TKAs. Conclusions These data could prove important for healthcare systems to appropriately allocate resources to hip and knee procedures: the revision burden for THA is 52% greater than for TKA, but revision TKAs are increasing at a faster rate. Likewise, the treating clinician should understand that while both revision THAs and TKAs bear significant clinical and economic costs, patients undergoing revision THA tend to be older, sicker, and have greater costs of care.

Speech perception in noise is a cognitively demanding process that challenges not only the auditory sensory system, but also cognitive networks involved in attention. The predictive coding theory has been influential in characterizing the influence of prior context on processing incoming auditory stimuli, with comparatively less research dedicated to “postdictive” processes and subsequent context effects on speech perception. Effects of subsequent semantic context were evaluated while manipulating the relationship of three target words presented in noise and the temporal position of targets compared to the subsequent contextual cue, demonstrating that subsequent context benefits were present regardless of whether the targets were related to each other and did not depend on the position of the target. However, participants instructed to focus on the relation between target and cue performed worse than those who did not receive this instruction, suggesting a disruption of a natural process of continuous speech recognition. We discuss these findings in relation to lexical commitment and stimulus-driven attention to short-term memory as mechanisms of subsequent context integration.

Background Patient, surgeon, health system, and device factors are all known to influence outcomes in THA. However, patient-related factors associated with an increased risk of early failure are poorly understood, particularly in elderly patients. Questions/purposes We identified specific demographic and clinical characteristics associated with increased risk of early revision in Medicare patients with THA. Methods The Medicare 5% national sample administrative database was used to calculate the relative risk of revision within 12 months following primary THA as a function of baseline medical comorbidities in 56,030 Medicare patients who underwent primary THA between 1998 and 2010. The impact of 29 comorbid conditions on risk of early revision was examined using Cox regression, controlling for age, sex, race, US Census region, socioeconomic status, and all other baseline comorbidities. Results Depression, rheumatologic disease, psychoses, renal disease, chronic urinary tract infection, and congestive heart failure were associated with revision THA within 12 months of the index arthroplasty (p ≤ 0.038 for all comparisons; risk factors listed in order of significance). Conclusions This information is important when counseling elderly patients with THA regarding the risk of early failure and for risk stratifying publicly reported outcomes in Medicare patients with THA. Level of Evidence Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

Rationale and objectivesThe reinforcement-enhancing effect (REE) of nicotine refers to the drug’s ability to enhance the strength of other primary and conditioned reinforcers. The main aim was to investigate neuropharmacological mechanisms underlying nicotine’s strengthening of a primary visual reinforcer (i.e., a light cue), using a subcutaneous (SC) dose previously shown to provide plasma nicotine levels associated with habitual smoking.MethodsAdult male rats pressed an “active” lever to illuminate a brief cue light during daily 60-min sessions. Rats that showed a clear REE were tested with systemically administered pretreatment drugs followed by nicotine (0.1 mg/kg SC) or saline challenge, in within-subject counterbalanced designs. Pretreatments were mecamylamine (nicotinic, 0.1-1 mg/kg SC), SCH 39166 (D1-like dopaminergic, 0.003-0.2 mg/kg SC), naloxone (opioid, 1 and 5 mg/kg SC), prazosin (alpha1-adrenergic antagonist, 1 and 2 mg/kg IP), rimonabant (CB1 cannabinoid inverse agonist, 3 mg/kg IP), sulpiride (D2-like dopaminergic antagonist, 40 mg/kg SC), or propranolol (beta-adrenergic antagonist, 10 mg/kg IP).ResultsThe nicotine REE was abolished by three antagonists at doses that did not impact motor output, i.e., mecamylamine (1 mg/kg), SCH 39166 (0.01 and 0.03 mg/kg), and naloxone (5 mg/kg). Prazosin and rimonabant both attenuated the nicotine REE, but rimonabant also suppressed responding more generally. The nicotine REE was not significantly altered by sulpiride or propranolol.ConclusionsIn adult male rats, the reinforcement-enhancing effect of low-dose nicotine depends on nicotinic receptor stimulation and on neurotransmission via D1/D5 dopaminergic, opioid, alpha1-adrenergic, and CB1 cannabinoid receptors.

Background The growth of consumer-directed health plans has sparked increased demand for information regarding the cost and quality of healthcare services, including total joint arthroplasty (TJA). However, the factors that influence patients’ choice of provider when pursuing elective orthopaedic care, such as TJA, are poorly understood. Questions/purposes We evaluated the factors patients consider when selecting an orthopaedic surgeon and hospital for TJA. Methods Two hundred fifty-one patients who sought treatment from either an academic or community-based orthopaedic practice for primary TJA completed a 37-item survey using a 5-point Likert scale rating (“unimportant” to “very important”) regarding seven established clinical and nonclinical dimensions of care patients considered when selecting a provider and hospital. Result Patients rated physician manner (average Likert, 4.7) and physician quality (eg, outcomes) (average Likert, 4.6) as most important in their selection of surgeon and hospital for TJA. Despite the expressed importance of surgeon and hospital quality, only 46% of patients were able to find useful information to compare outcomes among surgeons, and 47% for hospitals that perform TJA. Conclusions Our findings suggest physician manner and surgical outcomes are the most important considerations for patients when choosing a provider for elective TJA. Cost sharing is the least important criterion patients considered. Patients expressed high motivation to seek out provider quality information but indicated accessible and actionable sources of information are lacking. Future efforts should be directed at developing clinically relevant, easily interpretable, objective, risk-adjusted measures of physician and hospital quality.

Three-dimensional ceramic nanostructured films were produced from silicon-containing triblock copolymer films exhibiting the double gyroid and inverse double gyroid morphologies (space group Ia3d ). A one-step room-temperature oxidation process that used ozonolysis and ultraviolet irradiation effected both the selective removal of the hydrocarbon block and the conversion of the silicon-containing block to a silicon oxycarbide ceramic stable to 400°C. Depending on the relative volume fraction of the hydrocarbon block to the silicon- containing block, either nanoporous or nanorelief structures were fabricated with calculated interfacial areas of ∼40 square meters per gram and pore or strut sizes of ∼20 nanometers.

Here we examine the functions of the Myc cofactor and histone acetyltransferase, GCN5/KAT2A, in neural stem and precursor cells (NSC) using a conditional knockout approach driven by nestin-cre. Mice with GCN5-deficient NSC exhibit a 25% reduction in brain mass with a microcephaly phenotype similar to that observed in nestin-cre driven knockouts of c- or N-myc. In addition, the loss of GCN5 inhibits precursor cell proliferation and reduces their populations in vivo, as does loss of N-myc. Gene expression analysis indicates that about one-sixth of genes whose expression is affected by loss of GCN5 are also affected in the same manner by loss of N-myc. These findings strongly support the notion that GCN5 protein is a key N-Myc transcriptional cofactor in NSC, but are also consistent with recruitment of GCN5 by other transcription factors and the use by N-Myc of other histone acetyltransferases. Putative N-Myc/GCN5 coregulated transcriptional pathways include cell metabolism, cell cycle, chromatin, and neuron projection morphogenesis genes. GCN5 is also required for maintenance of histone acetylation both at its putative specific target genes and at Myc targets. Thus, we have defined an important role for GCN5 in NSC and provided evidence that GCN5 is an important Myc transcriptional cofactor in vivo.